Almonertinib as a neoadjuvant therapy for patients with a superior pulmonary sulcus tumor with activated EGFR mutation: A case report.

A superior pulmonary sulcus tumor, also known as a Pancoast tumor, invades tissues or organs at the entrance of the thorax, such as the brachial plexus, upper ribs, vertebrae, subclavian vessels and stellate ganglia. Induction concurrent chemoradiotherapy followed by radical surgical resection is the preferred treatment. The present study reported the case of a 52-year-old male who presented at Hubei Cancer Hospital, Tongji Medical College (Wuhan, Hubei) with left chest pain and an abnormal chest computed tomography scan showing a mass of 81x43 mm in the left upper chest wall that invaded the first, second and third anterior ribs. Biopsy of the mass showed stage cT4N0M0, IIIA, poorly differentiated adenocarcinoma and epidermal growth factor receptor+. The patient was treated by induction chemotherapy and targeted therapy, which was followed by surgical resection of the left upper lobe and the affected chest wall via the transmanubrial approach. The targeted therapy with almonertinib was continued postoperatively. To date, no disease recurrence has been detected during the 4 months follow-up.

Role of SLC44A3-AS1 Enhancer RNA in Esophageal Cancer Prognosis.

OBJECTIVE: To identify key enhancer RNAs (eRNA) in esophageal cancer through a comprehensive analysis and explore its importance in esophageal cancer. STUDY DESIGN: An observational study. Place and Duration of the Study: Department of Thoracic Surgery, Hubei Cancer Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China, from September to October 2022. METHODOLOGY: RNA-sequencing data, survival data, and clinical data for a total of 33 tumours were gathered from TCGA (The Cancer Genome Atlas) datasets. The survival-associated eRNAs were detected by means of Spearman's correlation and Kaplan-Meier survival analyses. Enhancer RNAs linked to survival rate and their target genes in esophageal cancer were screened, and a clinical correlation analysis of key eRNAs was carried out. A functional enrichment analysis was performed and the selected key eRNAs were confirmed in pan-cancer. RESULTS: The key eRNA was identified as SLC44A3-AS1, and patients with higher expression of SLC44A3-AS1 had worse prognosis than those with low expression. SLC44A3-AS1 expression was significantly associated with many clinical traits, namely tumour status, grade, pathological tumour, node, metastasis (TNM) stage, tumour type, etc. According to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment results, SLC44A3 may affect the prognosis of esophageal cancer patients through the herpes simplex virus 1 (HSV1) infection pathway. According to pan-cancer validation results, SLC44A3-AS1 was related to the survival of eight tumours. Correlations were observed between SLC44A3-AS1 and SLC44A3 in 32 types of tumours. CONCLUSION: SLC44A3-AS1 plays a key role in esophageal cancer related to prognosis, which may be a new therapeutic target for clinical exploration. KEY WORDS: SLC44A3-AS1, Enhancer RNA, Esophageal cancer, Prognosis.

MYH9 is a novel cancer stem cell marker and prognostic indicator in esophageal cancer that promotes oncogenesis through the PI3K/AKT/mTOR axis.

MYH9 encodes the heavy chain of nonmuscle myosin IIA, a ubiquitously expressed cytoplasmic myosin that regulates the actin cytoskeleton, cell migration, cell polarization, and signal transduction in cancer cells. Here, we investigated the role of MYH9 in cancer stem cells (CSCs) associated with esophageal cancer (EC). The subcellular localization of MYH9 was investigated in SKGT-4 cells through immunofluorescent analysis. MYH9+ and MYH9- spheroid cells were derived from SKGT-4 cells by flow cytometry and compared for self-renewal capacity, tumorigenicity, CD133 positivity, cisplatin resistance, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) activity. MYH9 messenger RNA expression was assessed in 30 EC patients by quantitative reverse transcription-polymerase chain reaction. Kaplan-Meier curves were plotted to explore the influence of MYH9 on EC survival. MYH9 localized to the plasma membrane, cytoplasm, and nucleus of SKGT-4 cells. Spheroid cells displayed higher MYH9 expression and positivity compared to parental SKGT-4 cells. MYH9+ cells showed strong CSC characteristics, including in vivo tumorigenicity, migration, invasion, cisplatin resistance, and CD133+ positivity. MYH9 activated the PI3K/AKT/mTOR axis in CSCs and was upregulated in EC patients with poor survival. Collectively, these data show that MYH9 significantly promotes tumorigenesis by regulating PI3K/AKT/mTOR signaling in EC. MYH9 expression remarkably correlates with poor prognosis and represents a novel biomarker and drug target for the diagnosis and treatment of EC.

Esophageal cancer with a double aortic arch: a case report and literature review.

BACKGROUND: Double aortic arch (DAA) is an extremely rare vascular malformation, even more so when coexisting with esophageal cancer. METHODS: We report a new case of DAA with esophageal cancer recently seen at our Thoracic Tumor Clinic and review cases of DAA coexisting with esophageal cancer reported in the literature of English language from 2010 to 2020. The purposes of our literature review were to explore how to best achieve radical esophagectomy while reducing postoperative complications. The clinical manifestations, diagnostic method, surgical approach, reconstruction route, and the extent of lymphadenectomy of esophageal cancer with DAA were analyzed in detail. RESULTS AND CONCLUSION: For such patients, 3D computed tomography is necessary for preoperative diagnosis. The surgical approach should consider factors such as the location of the tumor in the esophagus and whether the tumor is surrounded by DAA, as well as the position of the descending aorta and the requirements for the surgical field for lymphadenectomy. If esophageal reconstruction is required, the retrosternal route is preferred. We recommend that only patients with positive results of intraoperative frozen biopsy of recurrent laryngeal nerve lymph nodes should undergo three-field lymphadenectomy, which may be the best method to achieve radical esophagectomy for middle and lower esophageal cancers with DAA while minimizing postoperative complications.

A Low Advanced Lung Cancer Inflammation Index Predicts a Poor Prognosis in Patients With Metastatic Non-Small Cell Lung Cancer.

Introduction: Inflammation plays a crucial role in cancers, and the advanced lung cancer inflammation index (ALI) is considered to be a potential factor reflecting systemic inflammation. Objectives: This work aimed to explore the prognostic value of the ALI in metastatic non-small cell lung cancer (NSCLC) and classify patients according to risk and prognosis. Methods: We screened 318 patients who were diagnosed with stage IV NSCLC in Hubei Cancer Hospital from July 2012 to December 2013. The formula for ALI is body mass index (BMI, kg/m2) × serum albumin (Alb, g/dl)/neutrophil-lymphocyte ratio (NLR). Categorical variables were analyzed by the chi-square test or Fisher's exact test. The overall survival (OS) rates were analyzed by the Kaplan-Meier method and plotted with the R language. A multivariate Cox proportional hazard model was used to analyze the relationship between ALI and OS. Results: According to the optimal cut-off value determined by X-tile software, patients were divided into two groups (the ALI <32.6 and ALI ≥32.6 groups), and the median OS times were 19.23 and 39.97 months, respectively (p < 0.01). A multivariable Cox regression model confirmed that ALI and chemotherapy were independent prognostic factors for OS in patients with NSCLC. OS in the high ALI group was better than that in the low ALI group (HR: 1.39; 95% CI: 1.03-1.89; p = 0.03). Conclusions: Patients with a low ALI tend to have lower OS among those with metastatic NSCLC, and the ALI can serve as an effective prognostic factor for NSCLC patients.

Prognostic Prediction Models Based on Clinicopathological Indices in Patients With Resectable Lung Cancer.

Serum enzymes, blood cytology indices, and pathological features are associated with the prognosis of patients with lung cancer, and we construct prognostic prediction models based on clinicopathological indices in patients with resectable lung cancer. The study includes 420 patients with primary lung cancer who underwent pneumonectomy. Cox proportional hazards regression was conducted to analyze the prognostic values of individual clinicopathological indices. The prediction accuracies of models for overall survival (OS) and progression-free survival (PFS) were estimated through Harrell's concordance indices (C-index) and Brier scores. Nomograms of the prognostic models were plotted for individualized evaluations of death and cancer progression. We find that the prognostic model based on alkaline phosphatase (ALP), lactate dehydrogenase (LDH), age, history of tuberculosis, and pathological stage present exceptional performance for OS prediction [C-index: 0.74 (95% CI, 0.69-0.79) and Brier score: 0.10], and the prognostic model based on ALP, LDH, and platelet distribution width (PDW), age, pathological stage, and histological type presented outstanding performance for PFS prediction [C-index: 0.71 (95% CI, 0.66-0.75) and Brier score: 0.18]. These findings show that the models based on clinicopathological indices might serve as economic and efficient prognostic tools for resectable lung cancer.

lncRNA HOXB-AS3 exacerbates proliferation, migration, and invasion of lung cancer via activating the PI3K-AKT pathway.

Lung cancer remains the leading cause of cancer-related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB-AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB-AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB-AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB-AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB-AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB-AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB-AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.

Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design.

Antibiotic resistance is a growing global challenge to public health. Polymyxin is considered to be the last-resort antibiotic against most gram-negative bacteria. Recently, discoveries of a plasmid-mediated, transferable mobilized polymyxin resistance gene (mcr-1) in many countries have heralded the increased threat of the imminent emergence of pan-drug-resistant super bacteria. MCR-1 is an inner membrane protein that enables bacteria to develop resistance to polymyxin by transferring phosphoethanolamine to lipid A. However, the mechanism associated with polymyxin resistance has yet to be elucidated, and few drugs exist to address this issue. Here, we review our current understanding regarding MCR-1 and small molecule inhibitors to provide a detailed enzymatic mechanism of MCR-1 and the associated implications for drug design.

ASAP3 is a downstream target of HIF-1α and is critical for progression of lung adenocarcinoma.

Background: ASAP3 was first identified as a protein that promotes cell proliferation in hepatocellular carcinoma and later reported to be an Arf6-specific Arf GTPase-activating protein that regulates cell migration associated with cancer cell invasion. Materials and methods: Patients and tissue samples were from Hubei Cancer Hospital, human lung adenocarcinoma cell lines were obtained from the cell bank of the Chinese Academy of Science, nude mice (BALB/c nu/nu) were obtained from Shanghai SLAC Laboratory Animal Co. Ltd. Our methods contained immunohistochemistry, Western blotting, reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, stable transfection of lung adenocarcinoma cells, chromatin immunoprecipitation (CHIP) and luciferase assay, wound healing and cell migration assay. Results: In this study, we show that ASAP3 overexpression promotes migration and invasiveness in human lung adenocarcinoma cells and accelerates tumor progression in a xenograft mouse model. In patient tumor samples, ASAP3 overexpression was significantly associated with lymph node metastasis and reduced overall survival. We also show that ASAP3 expression is induced under hypoxic conditions through hypoxia-inducible factor 1α (HIF-1α), which binds directly to HER1 or/and HER2 (hypoxia response element) in the ASAP3 promoter. ASAP3 overexpression counteracts the inhibition of lung adenocarcinoma progression caused by HIF-1α knockdown both in vitro and in vivo. Conclusion: Our results identify ASAP3 as a downstream target of HIF-1α that is critical for metastatic progression in lung adenocarcinoma.

Genetic and pharmacological inhibition of eIF4E effectively targets esophageal cancer cells and augments 5-FU's efficacy.

BACKGROUND: Aberrant activation of eIF4E is critically involved in the progression and chemoresistance of various cancers. Elevated expression of eIF4E has also been documented in human cancerous esophageal tissues. However, the role of eIF4E in esophageal cancer is unclear. METHODS: We analysed the levels of eIF4E expression and eIF4E function in a number of normal and cancerous esophageal cancer cell lines, and studied its underlying mechanism. RESULTS: We observed that eIF4E expression varies in different esophageal cancer cell lines but was significantly elevated in all tested esophageal cell lines as compared to the control cell lines. We demonstrated that eIF4E inhibition via genetic and pharmacological approaches inhibits cancer cell growth and survival. This inhibition also augments 5-flurouracil's (5-FU's) efficacy as demonstrated with both the in vitro esophageal cancer culture system and our in vivo xenograft mouse model. Of note, the sensitivity of esophageal cancer cells to ribavirin or eIF4E knockdown correlates well with the expression levels of eIF4E, demonstrating that esophageal cells with higher eIF4E expression are more sensitive to eIF4E inhibition. We further confirmed that the mechanism of action of ribavirin on esophageal cancer cells was through suppressing the Akt/mTOR/eIF4E and eIF4E-regulated pathways. CONCLUSIONS: To our knowledge, our work is the first to demonstrate the multiple roles of eIF4E in esophageal cancer. eIF4E was shown to promote cancer cell growth and survival, and protected the cells from chemotherapy. Our work also demonstrated that ribavirin is an attractive candidate for the treatment of esophageal cancer.

Post-radiotherapy maintenance treatment with fluticasone propionate and salmeterol for lung cancer patients with grade III radiation pneumonitis: A case report.

RATIONALE: This combination of fluticasone propionate (FP) and the long-acting ß2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.

Video-assisted thoracic surgery right sleeve lobectomy.

A 50-year-old active male with a smoking history of 30 years (20 cigarettes per day) was admitted to hospital because of more than one month's cough without sputum. No comorbidity was present. The preoperative examination showed: blood test normal, ECG normal, cardio-pulmonary function normal, chest computed tomography (CT) display right upper lobe (RUL) mass of 5 cm diameter. Bronchoscopy examination and biopsy indicated large cell neuroendocrine carcinoma (LCNEC) in the take-off of RUL bronchus. No metastatic focus was found after emission computed tomography (ECT) scan of whole body bone, abdominal US scanning and brain MR. After initial evaluation, the clinical stage before operation was cT2bN0M0 (IIA stage). A selective video-assisted thoracic surgery (VATS) operation was arranged after 9 days of smoking cessation. Lateral position, one 10 mm trocar for camera in the 7th intercostals space in the mid-auxiliary line, 4 cm trocar for operation in the 4th intercostal space in the anterior axillary line, 15 mm trocar for auxiliary operation in the 8th intercostal space in the scapula line, the patient received VATS RUL lobectomy, plus systemic mediastinal lymph nodes dissection. The procedure of 200 minutes operation was smooth with blood loss of about 150 mL. Chest tube was removed 6 days after operation, and the patient discharged 11 days after the operation; The post-operation pathological examination showed RUL LCNEC, and the pathological stage was pT2bN0M0R0 (IIA stage). The patient has received four cycles of EP adjuvant chemotherapy per 21 days and is still alive without disease recurrence and metastasis after re-examination.