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1.
Alvaro Quintanal-Villalonga Sonia Molina-Pinelo Cristina Cirauqui Laura Ojeda-Márquez Ángela Marrugal Rocío Suarez Esther Conde Santiago Ponce-Aix Ana Belén Enguita Amancio Carnero Irene Ferrer Luis Paz-Ares 《Journal of thoracic oncology》2019,14(4):641-655
Introduction
There is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma.Methods
We performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogate and interaction assays. We performed monotherapy and combination EGFR/FGFR inhibitor sensitivity assays in vitro and in vivo in cell line– and patient-derived xenografts. We determined FGFR1 mRNA expression in a cohort of patients with anti–EGFR therapy–treated adenocarcinoma.Results
We have reported a cooperative interaction between FGFR1 and EGFR in this context, resulting in increased EGFR activation and oncogenic signaling. We have provided in vitro and in vivo evidence indicating that FGFR1 expression increases tumorigenicity in cells with high EGFR activation in EGFR-mutated and EGFR wild-type models. At the clinical level, we have shown that high FGFR1 expression levels predict higher resistance to erlotinib or gefitinib in a cohort of patients with tyrosine kinase inhibitor–treated EGFR-mutated and EGFR wild-type lung adenocarcinoma. Dual EGFR and FGFR inhibition in FGFR1-overexpressing, EGFR-activated models shows synergistic effects on tumor growth in vitro and in cell line– and patient-derived xenografts, suggesting that patients with tumors bearing these characteristics may benefit from combined EGFR/FGFR inhibition.Conclusion
These results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR inhibitors for selected patients with increased FGFR1 overexpression and EGFR activation. 相似文献2.
Chih-An Lin Sung-Liang Yu Hsuan-Yu Chen Huei-Wen Chen Shr-Uen Lin Chia-Ching Chang Chong-Jen Yu Pan-Chyr Yang Chao-Chi Ho 《Journal of thoracic oncology》2019,14(3):513-526
Introduction
Approximately 5% of patients with EGFR-activating mutations acquire EGFR tyrosine kinase inhibitor (TKI) resistance through SCLC transformation. However, the reason for the poor outcome and the molecular basis of EGFR-mutant SCLC that has transformed from adenocarcinoma remain unclear.Methods
In this study, we established two EGFR-mutant SCLC cell lines from lung adenocarcinoma patients after failed EGFR-TKI treatment to investigate their molecular basis and potential therapeutic strategies in the hope of improving patient outcome.Results
These two EGFR-mutant SCLC cell lines displayed two different phenotypes: suspensive and adherent. Both phenotypes shared the same genomic alterations analyzed by array-based comparative genomic hybridization assay. Increased expression of EGFR and mesenchymal markers and decreased expression of neuroendocrine markers were observed in adherent cells. Principal component analysis and hierarchical clustering analysis of RNA microarray revealed that these two cell lines displayed a unique gene expression pattern that was distinctly different from that in NSCLC and classical SCLC cells. Combined treatment using an EGFR-TKI and an AKT inhibitor attenuated cell viabilities in our two cell lines. Moreover, the use of a histone deacetylase inhibitor significantly inhibited the cell viabilities of both cell lines in vitro and in vivo.Conclusion
Our findings suggest that EGFR-mutant SCLC may be a distinct subclass of SCLC that exhibits epithelial-mesenchymal transition phenotypes, and adding an AKT or histone deacetylase inhibitor to pre-existing therapies may be one of the therapeutic choices for transformed EGFR-mutant SCLC. 相似文献3.
Christian Vogel Brigitte Ziegelmüller Börje Ljungberg Karim Bensalah Axel Bex Steven Canfield Rachel H. Giles Milan Hora Markus A. Kuczyk Axel S. Merseburger Thomas Powles Laurence Albiges Fiona Stewart Allseandro Volpe Anno Graser Marcus Schlemmer C. Yuan Thomas Lam Michael Staehler 《Clinical genitourinary cancer》2019,17(2):e345-e355
Objective
To systematically assessed the diagnostic performance of contrast-enhanced computed tomography (CT) compared to other imaging modalities for diagnosing and staging renal-cell carcinoma in adults.Methods
A comprehensive literature search was conducted through various electronic databases. Data from the selected studies were extracted and pooled, and median sensitivity and specificity were calculated wherever possible. Forty studies analyzing data of 4354 patients were included. They examined CT, magnetic resonance imaging (MRI), positron emission tomography–CT, and ultrasound (US).Results
For CT, median sensitivity and specificity were 88% (interquartile range [IQR] 81%-94%) and 75% (IQR 51%-90%), and for MRI they were 87.5% (IQR 75.25%-100%) and 89% (IQR 75%-96%). Staging sensitivity and specificity for CT were 87% and 74.5%, while MRI showed a median sensitivity of 90% and specificity of 75%. For US, the results varied greatly depending on the corresponding technique. Contrast-enhanced US had a median diagnostic sensitivity of 93% (IQR 88.75%-98.25%) combined with mediocre specificity. The diagnostic performance of unenhanced US was poor. For positron emission tomography–CT, diagnostic accuracy values were good but were based on only a small amount of data. Limitations include the strong heterogeneity of data due to the large variety in imaging techniques and tumor histotypes. Contrast-enhanced CT and MRI remain the diagnostic mainstay for renal-cell carcinoma, with almost equally high diagnostic and staging accuracy.Conclusion
For specific questions, a combination of different imaging techniques such as CT or MRI and contrast-enhanced US may be useful. There is a need for future large prospective studies to further increase the quality of evidence. 相似文献4.
5.
Paola Morelato Assunção Tamires Prates Lana Márcia Torresan Delamain Gislaine Oliveira Duarte Roberto Zulli Irene Lorand-Metze Carmino Antonio de Souza Erich Vinicius de Paula Katia Borgia Barbosa Pagnano 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):162-166
Background
Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors.Patients and Methods
We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively.Results
The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality.Conclusion
CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk. 相似文献6.
Yutong Wang Li Bao Bin Chu Shan Gao Minqiu Lu Lei Shi Lina Fu Lijuan Fang Qiuqing Xiang 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):167-176.e1
Background
Patients with multiple myeloma (MM) are at risk of cardiovascular events (CVEs) as a result of disease burden– and treatment-related risk factors. Cardiac biomarkers have been reported to be more sensitive than left ventricular ejection fraction in detecting CVEs. We sought to explore CVEs risk factors in MM patients and to establish sensitive predictors of biomarkers.Patients and Methods
We studied 116 newly diagnosed MM patients who received chemotherapy in our department. Echocardiograms were examined at baseline and after 4 cycles of treatment, as well as upon clinical suspicion of a cardiac event or after an adjustment of treatment regimens. Cardiac biomarkers, including troponin T, myohemoglobin, and N terminal pro B-type natriuretic peptide (NT-proBNP), were estimated before each cycle and within 24 hours after chemotherapy, which was provided for at least 4 cycles.Results
Thirteen patients (11.2%) experienced CVEs, seven of which were subclinical. There was no significant difference between the CVE group and the non-CVE group in terms of general patient characteristics, MM disease factors, or chemotherapy drugs. The baseline levels of left ventricular ejection fraction and NT-proBNP were comparable between the 2 groups. NT-proBNP levels increased rapidly after chemotherapy and fell to normal levels before administration of the next cycle in all patients (60 pg/mL vs. 446 pg/mL, P < .001). Patients with asymptomatic CVEs showed a significantly higher proportion of progressively elevated NT-proBNP compared to symptomatic CVE and non-CVE patients (57% vs. 0 vs. 6.1%, P = .035).Conclusion
The dynamic change in NT-proBNP may predict early asymptomatic cardiac damage and allow interventional strategies to avoid cardiac decompensation. 相似文献7.
Michiel A. IJsseldijk Melina Shoni Charles Siegert Bastiaan Wiering K.C. Anton van Engelenburg Abraham Lebenthal Richard P.G. ten Broek 《Journal of thoracic oncology》2019,14(4):583-595
Introduction
Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC.Methods
The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates.Results
A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease.Conclusions
Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy. 相似文献8.
Baoan Hong Lin Cai Jiangyi Wang Shengjie Liu Jingcheng Zhou Kaifang Ma Jiufeng Zhang Bowen Zhou Xiang Peng Ning Zhang Kan Gong 《Clinical genitourinary cancer》2019,17(2):97-104.e1
Background
Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.Patients and Methods
Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry. Correlations between PD-L1 expression and clinicopathological features were analyzed.Results
In sporadic ccRCC, the positive expression rate of PD-L1 was 47.3% (61/129). Positive PD-L1 expression was correlated with advanced tumor T stage (P = .011), higher Fuhrman nuclear grade (P = .022), poor disease-free survival (P = .037), and sex (P = .025). In the VHL-associated hereditary ccRCC, positive PD-L1 expression rate was 34.6% (9/26), lower than that in sporadic ccRCC. Positive PD-L1 was correlated with higher Fuhrman nuclear grade (P = .008), but not with sex, age, tumor stage, or the onset age of VHL-associated tumors.Conclusion
Positive PD-L1 expression was correlated with the aggressive clinicopathological features in sporadic and VHL-associated hereditary ccRCC. Whether PD-L1 expression level in ccRCC is related to the effectiveness of programmed death-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated. 相似文献9.
Purpose
To assess the pharmacologic costs of second-line treatments for metastatic renal-cell cancer (mRCC).Methods
The present evaluation was restricted to pivotal phase 3 randomized controlled trials in second-line for mRCC. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival and overall survival (OS) for each trial. The costs of drugs are at the pharmacy of our hospital and are expressed in euros.Results
Our analysis evaluated 5 phase 3 randomized controlled trials including 3112 patients. The lowest cost per month of progression-free survival and OS gained was associated with the use of cabozantinib (€2006 and €1473, respectively), while everolimus had the highest cost per month of OS gained (€28,590).Conclusion
Combining pharmacologic costs of drugs with the measure of efficacy represented by OS, cabozantinib is a cost-effective second-line treatments for patients with mRCC. 相似文献10.
Uday Yanamandra Prateek Deo Kamal Kant Sahu Ram Vasudevan Nampoothiri Nalini Gupta Anusree Prabhakaran Deb Prasad Dhibhar Alka Khadwal Gaurav Prakash Man Upadesh Singh Sachdeva Deepesh Lad Neelam Varma Subhash Varma Pankaj Malhotra 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):183-189.e1
Background
Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.Patients and Methods
In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes.Results
Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months.Conclusion
MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis. 相似文献11.
Pashtoon Murtaza Kasi Faisal Shahjehan Jordan J. Cochuyt Zhuo Li Dorin Toma Colibaseanu Amit Merchea 《Clinical colorectal cancer》2019,18(1):e87-e95
Background
Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.Patients and Methods
This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear.Results
The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and right-sided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001).Conclusion
Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised. 相似文献12.
Omar Abdel-Rahman 《Clinical genitourinary cancer》2019,17(2):e329-e338
Background
The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.Patients and Methods
Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.Results
A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.Conclusion
Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial. 相似文献13.
Atsunari Kawashima Takayuki Kanazawa Kentaro Jingushi Taigo Kato Takeshi Ujike Akira Nagahara Kazutoshi Fujita Akiko Morimoto-Okazawa Kota Iwahori Motohide Uemura Ryoichi Imamura Hisashi Wada Norio Nonomura 《Clinical genitourinary cancer》2019,17(2):114-124
Background
There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma.Patients and Methods
Tumor tissue–infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival).Results
The immunologic condition was classified into 2 groups. Group 1 (n = 41) comprised the CD4 T-cell–dominant group and group 2 (n = 29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P = .020) but not tumor location in multivariate analysis. In invasive BCa patients (n = 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P = .021 and P = .022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n = 17).Conclusion
Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site. 相似文献14.
Morana Vojnic Daisuke Kubota Christopher Kurzatkowski Michael Offin Ken Suzawa Ryma Benayed Adam J. Schoenfeld Andrew J. Plodkowski John T. Poirier Charles M. Rudin Mark G. Kris Neal X. Rosen Helena A. Yu Gregory J. Riely Maria E. Arcila Romel Somwar Marc Ladanyi 《Journal of thoracic oncology》2019,14(5):802-815
15.
Purpose
This study aimed to determine the pain response rates after conventional radiation therapy (RT) for painful bone metastases in prospective nonrandomized studies, which better reflect daily practice than randomized controlled trials.Methods and materials
A literature search was conducted in PubMed and Scopus for articles published between 2002 and 2018. We only included articles in which pain response after RT was assessed using the International Consensus Endpoint initially published in 2002, or the updated version from 2012. In addition, to be included in this review, the study design was required to be prospective or based on prospectively collected data. Our primary outcomes of interest were the overall and complete response rates after conventional RT for bone metastases.Results
Of the 2863 articles identified in our database search, 12 met the inclusion criteria. Six studies excluded patients with features of complicated bone metastases. Only 2 papers reported exclusion criteria regarding analgesic use. Radiation schedules that were frequently used were 1 × 8 Gy, 5 × 4 Gy, and 10 × 3 Gy. The overall response rate in evaluable patients was 55%, and 754 of the 1379 evaluable patients experienced a complete or partial response. The complete response rate was 15% (196 of 1348 evaluable patients). In the intent-to-treat patient group, the overall response rate was 29% (754 of 2559 enrolled patients), and the complete response rate 8% (196 of 2528 enrolled patients).Conclusions
We determined the pain response rates after conventional RT for painful bone metastases in prospective nonrandomized studies. The present review may provide benchmarks for future nonrandomized studies that investigate palliative RT for bone metastases. 相似文献16.
17.
Chao Zhang Shao-lei Li Qiang Nie Song Dong Yang Shao Xue-ning Yang Yi-long Wu Yue Yang Wen-zhao Zhong 《Journal of thoracic oncology》2019,14(4):726-731
Background
Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease.Methods
We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib. All the patients were treatment naive and received crizotinib at a starting dose of 250 mg twice daily. Patient 3 was provided with dynamic monitoring before and after neoadjuvant therapy through next-generation sequencing of plasma and tissue. In case 4, next-generation sequencing of preoperative tissue was performed.Results
Of the 11 patients, 10 had a partial response and one was stable disease after neoadjuvant crizotinib, with one suffering from grade 4 hepatic damage. Of the 11 patients, 10 (91.0%) received an R0 resection and 2 patients achieved a pathological complete response to neoadjuvant crizotinib. Six patients had disease recurrence, with five of them receiving crizotinib as first-line treatment and achieving a long duration of response. Dynamic monitoring of both plasma and tissue simultaneously indicated a decrease in sensitive ALK signaling in patient 3 and a partial response (approximately 50% of partial response), and no ALK-dependent resistance variants were captured.Conclusion
Neoadjuvant crizotinib may be feasible and well tolerated in locally advanced disease for complete resection. Crizotinib therapy before surgery may provide thorough elimination of circulating molecular residual disease and not influence the reuse of first-line crizotinib, but ongoing prospective trials are warranted to prove its efficacy in the neoadjuvant setting. 相似文献18.
Shun Lu Yongfeng Yu Ziming Li Ruoying Yu Xue Wu Hairong Bao Yan Ding Yang W. Shao Hong Jian 《Journal of thoracic oncology》2019,14(4):732-736
Introduction
Inherited genetic determinants of lung cancer risk remain relatively elusive. Germline mutations in EGFR and erb-b2 receptor tyrosine kinase 2 (ERBB2) have been previously reported in lung cancers that may be associated with genetic susceptibility to lung cancer.Methods
We retrospectively analyzed a cohort of 12,833 Chinese lung cancer patients tested by targeted next-generation sequencing. Patients with EGFR and ERBB2 germline mutations were identified, and their clinical information and family history were summarized. Growth factor independency of EGFR germline mutations was further analyzed in vitro.Results
Eight different heterozygous EGFR germline mutations from 14 adenocarcinoma patients (0.12%) were identified within or adjacent to the kinase domain, including K757R (n = 5), R831H (n = 2), D1014N (n = 2), G724S, V786M, T790M, L792F, and L844V. Only one patient harbored the ERBB2-V1128I germline mutation. Five of 15 patients had family history of cancer. Notably, the patient with EGFR-T790M germline mutation had multiple maternal family members diagnosed with lung cancers, strongly supporting its role in inherited lung cancer. Concurrent known somatic driver mutations were not detected in 5 patients at diagnosis, 1 of whom harbored the EGFR-L844V germline mutation and showed superior response to afatinib. Consistently, EGFR-K757R and L844V mutations were able to be interleukin 3 – independent in vitro and were sensitive to EGFR tyrosine kinase inhibitors.Conclusions
EGFR/ERBB2 germline mutations were found to be rare in Chinese lung cancer patients with more diversity other than the previously reported EGFR-T790M, with EGFR-K757R being the most common EGFR germline mutation. Patients with EGFR germline mutations without other known driver mutations might benefit from tyrosine kinase inhibitor treatment. 相似文献19.
Irina Druzhkova Nadezhda Ignatova Natalia Prodanets Nikolay Kiselev Iliya Zhukov Marina Shirmanova Vladimir Zagainov Elena Zagaynova 《Clinical colorectal cancer》2019,18(1):e74-e86
Background
The conventional chemotherapy of colorectal cancer with irinotecan, 5-fluorouracil, and oxaliplatin remains one of the front-line treatments worldwide. However, its efficacy is quite low. Recently studies of the epithelial–mesenchymal transition (EMT) have become the focus of investigations into the cause of chemoresistance in several types of cancer, including colorectal cancer. The data about the role of EMT in chemosensitivity are controversial.Materials and Methods
Human colon adenocarcinoma cell lines HT29 and HCT116 and 14 primary short-term cultures established from patient tumors were used. The chemosensitivity to irinotecan, 5-fluorouracil, and oxaliplatin was assessed using the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Immunocytochemistry, immunohistochemistry, and Western blot test were used to investigate the E-cadherin expression, the loss of which is a major hallmark of EMT.Results
Elevated chemosensitivity of the cell line with EMT phenotype, HCT116, was demonstrated. Increased chemosensitivity was revealed in HT29 cell line upon EMT induction. E-cadherin–positive short-term cultures were more resistant to all the drugs tested, whereas each of E-cadherin–negative cultures showed sensitivity to at least one drug. The statistically significant dependency of cells viability on the E-cadherin expression (P < .04) was demonstrated on the short-term cultures using 2 concentrations of each drug.Conclusion
The data obtained may serve as a basis for the analysis of colon cancer chemosensitivity using short-term cultures and the assay of E-cadherin expression. 相似文献20.
Chiara Adriana Pistolese Antonella Castrignanò Francesca Ricci Rosaria Meucci Giusy Croce Mariateresa Mondillo Alberto Collura Tommaso Perretta Roberto Floris 《Clinical breast cancer》2019,19(2):e352-e357