Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Unresectable stage Ⅲ non-small-cell lung cancer: Have we made any progress?

Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage ⅢA or stage ⅢB disease. The standard of care for locally advanceddisease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage Ⅲ non-small-cell lung cancer(NSCLC) remains poor. Improving outcomes for patients with unresectable stage Ⅲ NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo

Background： Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma （LLC） tumor in vivo. Methods： Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Results： Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature （2.20 ± 0.82）℃ as compared with the other groups （0.78 ± 0.29 ℃, 1.24 ± 0.52 ℃, 0.78 ± 0.42 ℃, respectively）, but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Conclusions： Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity Ibr a short time per day is promising in treating non-small-cell lung cancer.

EGFR突变NSCLC组织LncRNA TCF7L2表达及临床病理特征和预后分析

目的 探究长链非编码RNA(LncRNA)转录因子7类似物2(TCF7L2)在表皮生长因子受体基因(EGFR)突变的非小细胞肺癌(NSCLC)组织表达及其与病人临床病理特征和预后相关性。方法 选取2019年3月—2021年6月河北北方学院附属第一医院治疗的EGFR突变NSCLC病人104例为研究对象,分别取其癌组织和癌旁组织应用逆转录PCR(RT-PCR)检测LncRNA TCF7L2的表达,比较不同组织TCF7L2表达及其与临床病理特征和预后的相关性。结果 RT-PCR检测结果显示,癌组织中LncRNA TCF7L2表达量显著高于癌旁组织(t=12.410,P<0.05)。与LncRNA TCF7L2低表达病人比较,高表达者发生淋巴结转移更多、肿瘤体积更大(χ^(2)=4.579、7.762,P<0.05);LncRNA TCF7L2高表达病人6、9和12个月的生存率较低,但差异均无统计学意义(P>0.05)。结论 LncRNA TCF7L2在EGFR突变NSCLC病人癌组织表达高于癌旁组织,且TCF7L2高表达病人的淋巴结转移风险较高、肿瘤体积较大,其生存率可能较低。

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

11例原发性肺黏液表皮样癌的临床病理分析

目的 探讨原发性肺黏液表皮样癌(PMEC)的临床病理及分子特征。方法 回顾性分析11例2005年1月至2021年12月经手术切除并确诊为PMEC患者的临床病理资料,并复习相关文献。结果 11例患者中,男性7例,女性4例;年龄19~58岁,中位年龄33岁;肿瘤均发生于段及段以上支气管,临床以支气管刺激症状为主。胸部CT显示10例为边界尚清晰的类圆形结节,1例显示为不规则肿块,5例伴有浅分叶。11例肿块增强扫描后均显示轻-中度的不均匀强化,肿块内有钙化者5例。1例组织学分级为高级别PMEC,10例为低级别PMEC。免疫组织化学染色结果显示,瘤细胞CK7、p63及p40阳性,TTF1、NapsinA、CK20和SMA阴性,增殖指数Ki-67约4%~28%。特殊染色示黏液细胞PAS阳性。6例患者行MAML2的FISH检测,4例患者显示MAML2基因重排阳性。11例患者均行手术治疗,其中3例术后辅助化疗。8例患者随访8~144个月,1例高级别PMEC复发。结论 PMEC是一种罕见肿瘤,其诊断需结合病理组织学特点和免疫组化,FISH检测到MAML2基因易位,主要依据术后组织病理,手术是治疗的主要方法,其预后与病理分级及临床分期相关。

Molecular Mechanisms Contributing to Resistance to Tyrosine Kinase-Targeted Therapy for Non-Small Cell Lung Cancer

One of the most important pathways in non-small cell lung cancer(NSCLC) is the epidermal growth factor receptor(EGFR) pathway. This pathway affects several crucial processes in tumor development and progression,including tumor cell proliferation,apoptosis regulation,angiogenesis,and metastatic invasion.Targeting EGFR is currently being intensely explored.We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology.In the last decade,the tyrosine kinase(TK) domain of the EGFR was identified in NSCLC patients,and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib.Unfortunately,there were primary and/or secondary resistance to these treatments,as shown by clinical trials.Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon.The molecular mechanisms of resistance need to be clarified.An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.

肺癌患者血清CA724、CA153、SCC水平与病理特征及术后复发转移的关系

目的探讨肺癌(LC)患者血清糖类抗原724(CA724)、糖类抗原153(CA153)、鳞癌抗原(SCC)水平与病理特征及术后复发转移的关系。方法选取2019年6月至2020年12月在周口市中心医院接受手术治疗的102例LC患者,根据其2 a后是否存在复发转移分为复发转移组和未复发转移组,比较两组术前血清CA724、CA153和SCC水平及病理特征,分析影响术后复发转移的因素。结果随访后,102例患者中有65例发生复发转移,发生率为63.73%;复发转移组CA724、CA153和SCC水平均高于未复发转移组(P<0.05);腺癌组CA724水平高于小细胞肺癌组和鳞癌组(P<0.05),3组CA153水平差异无统计学意义(P>0.05);鳞癌组SCC水平高于小细胞肺癌组和腺癌组(P<0.05)。Ⅱ期和Ⅲ期CA724、CA153和SCC水平高于Ⅰ期(P<0.05)。复发转移组和未复发转移组TNM分期和分化程度差异有统计学意义(P<0.05)。Cox单因素回归分析结果显示,TNM分期、高水平CA724、CA153、SCC和分化程度是LC患者术后复发转移的影响因素(P<0.05);多因素回归分析结果显示,TNM分期为Ⅲ期和高水平的CA724、CA153和SCC均为影响LC患者术后复发转移的独立危险因素(P<0.05)。结论LC患者血清CA724、CA153、SCC表达水平与LC病理特征和术后复发转移关系密切,临床可通过检测血清CA724、CA153、SCC水平来评估术后复发转移情况。

肺转移性透明细胞肾细胞癌的临床病理学观察

目的探讨肺转移性透明细胞肾细胞癌临床病理学特点。方法回顾性分析4例穿刺活检诊断肺转移性透明细胞肾细胞癌的临床病理特征,采用免疫组化染色检测CK、p40、p63、TTF-1、Napsin A、PAX8、CD10,观察其表达情况。结果4例患者中,男3例,女1例,年龄44~71岁,平均58.75岁;均为双肺多发结节,其中各例最大的结节位于左下肺2例,右下肺2例。4例均表达CK、PAX8、CD10,而TTF-1、Napsin A、p40、p63阴性。结论具有透明细胞形态特点的肺肿瘤需要考虑肺转移性透明细胞肾细胞癌的可能。

Value of COX-2 and HER-2 in Judging Condition and Prognosis in Non-Small Cell Lung Cancer Patients

OBJECTIVE To investigate the expressions of cyclooxygenase 2 （COX-2） and human epidermal growth factor receptor-2 （HER-2） in non-small cell lung cancer （NSCLC） and their clinical significance in identifying the progression and prognosis of the NSCLC patients. METHODS Immunohistochemical indirect method was used to detect the expressions of the COX-2 and HER-2 protein in 54 NSCLC specimens, 16 paraneoplastic specimens, and 10 normal tissue specimens. RESULTS The positive rates of COX-2 and HER-2 protein expressions were respectively 75.9% and 40.7% in the NSCLC specimens, 25% and 12.5% in the paraneoplastic specimens, and 0 in the normal tissue. The COX-2 protein expression in lung cancer （LC） was not only related to the smoking habit of the patients and histological grades of LC, but also to the TNM stages, and lymphatic metastasis （P 〈 0.05）. HER-2 protein expression closely correlated to the pathologic types, histological grades, TNM stages, and lymphatic metastasis （P 〈 0.05）. The result of univariate analysis showed that all the histological grades, TNM stages, lymphatic metastasis, and expressions of COX-2/HER-2 correlated to the prognosis of NSCLC patients （mean of P value 〈 0.01）. The multivariate survival analysis indicated that there were signi.cant di.erences in comparison of the survival time between the COX-2 （＋＋/＋＋＋） /HER-2 （＋＋/＋＋＋） and the COX-2 （-/＋）/HER-2 （-/＋） groups （P〈 0.001）, suggesting the COX-2/HER-2 was a negative prognostic factor. CONCLUSION COX-2 and HER-2 are valuable in identifying the progression of NSCLC and predicting the prognosis of NSCLC patients. COX-2 and HER-2 are useful for judging the NSCLC patient＇s condition, and are of great value to the decision of NSCLC prognosis.

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

双重癌:左肺腺癌合并甲状腺内胸腺癌1例

多原发癌(MPC)又名重复癌,是指同一机体内同时或先后发生的两种或两种以上不相关的原发性恶性肿瘤。随着现代医学进步,多原发癌并不罕见,所有肿瘤患者的多原发恶性肿瘤(MPM)发病率约为0.73%~5.20%,这种广泛的差异与不同医院的医生和诊断工具不同有关。肺癌死亡率最高,由于低剂量肺癌筛查及人们健康意识的提高,大量早期肺癌被筛查出来,随着治疗方式的改进,如分子靶向治疗,使肺癌预后取得了大量进步,因此患者存活的时间足够长,可以发展为随后的原发肿瘤,但肺癌合并甲状腺内胸腺癌(ITTC)实属罕见。

血清SCCA、ProGRP、NSE与老年非小细胞肺癌患者病理特征及化疗客观疗效的相关性分析

目的 分析血清鳞状细胞癌抗原(SCCA)、胃泌素释放肽前体(ProGRP)、神经元特异性烯醇化酶(NSE)与老年非小细胞肺癌(NSCLC)患者病理特征及化疗客观疗效的相关性。方法 选取临泉县人民医院2020年10月~2023年5月收治的80例老年NSCLC患者,均接受规范化疗,根据化疗客观疗效分为部分缓解(PR)组、病情稳定(SD)组与疾病进展(PD)组,比较不同病理特征患者及不同化疗客观疗效组患者血清SCCA、ProGRP、NSE水平,并进行相关性分析。结果 Ⅳ分期、有淋巴结转移患者血清SCCA、ProGRP、NSE水平高于Ⅲ分期、无淋巴结转移患者,差异有统计学意义(P<0.05)。血清SCCA、ProGRP、NSE与患者TNM分期、淋巴结转移呈显著正相关(P<0.05)。PR组化疗后SCCA、ProGRP、NSE水平低于SD组、PD组;SD组化疗后SCCA、NSE水平低于PD组,差异均有统计学意义(P<0.05)。化疗后,SCCA、ProGRP、NSE与化疗客观疗效呈显著负相关(P<0.05)。结论 血清SCCA、ProGRP、NSE与老年NSCLC患者TNM分期、淋巴结转移情况及化疗客观疗效密切相关。