scholarly journals Spatial transcriptome sequencing revealed spatial trajectory in the Non-Small Cell Lung Carcinoma

2021 ◽  
Author(s):  
Li Zhang ◽  
Shengqiang Mao ◽  
Menglin Yao ◽  
Ningning Chao ◽  
Ying Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Tumor Metastasis ◽  
Small Cell Lung Carcinoma ◽  
Time Model ◽  
Cell Lung Carcinoma ◽  
Gene Expression Heterogeneity ◽  
Spatial Trajectory ◽  
Spatial Transition ◽  
Expression Gradients

Deepening understanding in the heterogeneity of tumors is critical for clinical treatment. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal lung cancer using the spatial transcriptomics (ST) technology. We identified gene expression gradients in stroma adjacent to tumor regions that allow for re-understanding of the tumor micro-environment. The establishment of these profiles was the first step towards an unbiased view of lung cancer and can serve as a dictionary for future studies. Tumor subclones were detected by ST technology in our research, while we contrast the EMT ability among in subclones which inferred the possible trajectory of tumor metastasis and invasion, which was confirmed by constructing the pseudo-time model of spatial transition within subclones. Together, these results uncovered lung cancer spatial heterogeneity, highlight potential tumor micro-environment differences and spatial evolution trajectory, and served as a resource for further investigation of tumor microenvironment.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

New lung cancer treatment strategy with molecular target of PKCeta

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 56-58
Author(s):  
Motoi Ohba
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Surgical Removal ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Nucleotide Mutation

Lung cancer is one of the most prevalent and lethal forms of the disease accounting for almost 20 per cent of all deaths from cancer. It is therefore the leading cause of cancer death in men and second most fatal in women. There are between 1.5 and 2 million new cases of cancer globally every year. A similar number die from the disease annually. There are two forms of lung cancer – small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). SCLC is the more aggressive form being faster growing and more metastatic, however it also responds more effectively to treatments such as chemotherapy. NSCLC is the more common form of the disease, accounting for 85 per cent of cases. They develop more slowly than SCLCs, however they are largely unresponsive to chemotherapy and require precise surgical removal. Both present a huge medical problem in terms of diagnosis and treatment. Due to its far higher prevalence, NSCLC is the most studied of the two forms. A chemotherapeutic treatment has been developed that targets the epidermal growth factor receptor (EGFR). EGFR is majorly upregulated in most cases and plays a key role in the tumour's growth and survival. The treatment blocks the receptor and is usually very effective in the first instances. However, it is typically unable to clear the cancer as a single nucleotide mutation is capable of rendering the inhibitor unable to act on the receptor. Therefore, the cancer returns and continues to develop. New treatments are also required. This is the work of Dr Motoi Ohba of the Advanced Cancer Translational Research Institute, Showa University, Japan. His work is aimed at both uncovering novel targets for cancer treatment and finding and developing molecules that could effectively manipulate these targets.

Targeted therapeutics for non small cell lung carcinoma

2019 ◽  
Author(s):  
◽  
Soumavo Mukherjee
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Environmental Pollutants ◽  
Ether Linkage ◽  
University Of Missouri ◽  
Cell Lung Carcinoma ◽  
Age Of Diagnosis ◽  
The University ◽  
Gene Expression Levels

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] "Lung carcinoma, also known as lung cancer, is a malignant tumor of lungs characterized by uncontrolled call growth in lung tissue. Tobacco smoking is the reason for nearly 85% of cases of lung cancer. The rest 10-15% are usually a combination of genetic factors, secondhand smoke, environmental pollutants, asbestos and radon gas exposure. Chest radiography and CT scan with confirmation by biopsy are the ways to detect the cancer. The type of cancer, degree of spread and the overall health weigh in on the outcome and eventual possible cure. Still now, most cases are not curable. Surgery, chemotherapy and radiotherapy are the treatments of choice for all types of lung cancer. Being the most common form of cancer in men and second most common form in women, after breast, data of the year 2012 showed 1.8 million incidences of lung cancer resulting to 1.6 million deaths worldwide, with the most common age of diagnosis being 70 years. 5-year survival rate in USA is 17.4%. ... Studies has been done to unravel the downstream effect after knocking down the oncogene via siRNA(42). Malignant cells have a number of secondary pathways, along with the primary pathway, which remain dormant till the disruption of the primary pathway(43). A complex mechanism controls this function which is triggered by the change in downstream protein and gene expression levels. This makes the cancer cells develop drug resistance(44). In this project, we developed a gelatin-based nanoparticle (GelNP) that will act as a vehicle to deliver targeted siRNAs against NSCLC cells in combination with Cisplatin. The cetuximab (Ab), an EGFR targeting antibody, shall be attached to the surface. The AXL and FN14 SiRNAs shall be conjugated to the antibody by the thio-ether linkage. The cetuximab antibody shall be used to specifically target the cell and also to protect the siRNAs from degradation. We predict that 146kDa cetuximab antibody will shield the 15kDa siRNAs and prevent it from exposure to environment. Since AXL and FN14 has been observed to be related to EGFR, we hypothesize that knocking down AXL and FN14 will block EGFR and thus allow the TKI to continue its course of therapeutic action."--Introduction.

scholarly journals GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

2021 ◽  
pp. 096032712110594
Author(s):  
Harleen Kaur Walia ◽  
Navneet Singh ◽  
Siddharth Sharma
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Small Cell Lung Carcinoma ◽  
Predictive Biomarker ◽  
Hematological Toxicity ◽  
Cell Lung Carcinoma ◽  
Mutant Genotype ◽  
Lung Cancer Patients ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

scholarly journals Diagnostic and Prognostic Potential of Circulating Long Non-Coding RNAs in Non Small Cell Lung Cancer

2018 ◽  
Vol 49 (2) ◽  
pp. 816-827 ◽  
Author(s):  
Wei Peng ◽  
Jun Wang ◽  
Bin Shan ◽  
Zhenzi Peng ◽  
Yeping Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Function ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Coding ◽  
Cell Lung Carcinoma ◽  
Therapeutic Modalities ◽  
Diagnosis And Prognosis ◽  
Non Coding Rnas

Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 80% of lung cancer cases are non–small cell lung carcinoma (NSCLC). However current diagnostic and therapeutic modalities against NSCLC are ineffective due to incomplete understanding of molecular pathogenesis of NSCLC. Emerging evidence shows that long non-coding RNAs (lncRNAs) can function as biomarkers for diagnosis and prognosis. LncRNAs can control transcription, translation, and protein function via diverse mechanisms although they lack the protein coding potential. LncRNAs have attracted intense investigations on their roles in cancer. Mounting evidence indicates that lncRNAs are promising biomarkers in diagnosis and prognosis for NSCLC, especially their presence in body fluids. Herein we will review recent advances in the research that explores the diagnostic and prognostic potentials of lncRNAs in NSCLC. We will also discuss emerging evidence that suggested lncRNAs as therapeutic targets in NSCLC.

Transthyretin (TTR) Suppressed Tumor Progression in Non-Small Cell Lung Cancer by Inactivating MAPK/ERK Pathway

2020 ◽  
Author(s):  
Dong-bin Wang ◽  
Xuan Li ◽  
Xi-ke Lu ◽  
Zhong-yi Sun ◽  
Xun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Clinical Care ◽  
Small Cell ◽  
Signal Pathways ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
In Vivo Experiments

Abstract Background: Lung cancer is a leading cause of cancer death around the world, while the Transthyretin (TTR) is a specific biomarkers for clinical diagnosis. However, its role in lung cancer remains to be unknown. Methods: In the present study, we made attempt to investigate effect of abnormal expression of TTR on Non-small-cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR.To further investigate the mechanisms underlying the potential role of TTR in NSCLC, we searched and verified several signal pathways . In vivo experiments, to verify the effect of TTR overexpression on tumors.Results: We finded that up-regulated TTR obviously suppressed cell proliferation, migration, invasion and increased apoptosis.Significant suppression of phosphor-MAPK/ERK was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating MAPK/ERK signaling pathway. In vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusions: Overall, our results suggest that TTR has a potential anti-tumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC.Above all, further understanding of TTR was useful for clinical care.

scholarly journals Detection of EGFR Mutations Using Bronchial Washing-Derived Extracellular Vesicles in Patients with Non-Small-Cell Lung Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2822
Author(s):  
Juhee Park ◽  
Chaeeun Lee ◽  
Jung Seop Eom ◽  
Mi-Hyun Kim ◽  
Yoon-Kyoung Cho
Keyword(s):  
Lung Cancer ◽  
Extracellular Vesicles ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Resistance Mutation ◽  
Detection Sensitivity ◽  
Egfr Mutations ◽  
Tissue Samples ◽  
Cell Lung Carcinoma ◽  
Bronchial Washing

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.

scholarly journals A Rare Case of Diffuse Subependymal Periventricular Metastases from Small Cell Lung Carcinoma

2020 ◽  
Vol 13 (3) ◽  
pp. 1304-1310
Author(s):  
Cong Thao Trinh ◽  
Thanh Tam Thi Nguyen ◽  
Hoang Anh Thi Van ◽  
Van Trung Hoang
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Brain Parenchyma ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Small cell lung cancer, whose essence is neuroendocrine tumors, makes up proximately 14–20% of all lung cancer circumstances. Compared to non-small cell lung cancer, its clinical manifestation seems more positive and has a tendency to disseminate earlier in the process of its natural past. About 10% of patients present with brain metastases at the time of provisional diagnosis and sometimes all along the course of their disease, there will be 40–50% of developed brain metastases in addition. Although metastases in the brain parenchyma are often found in patients with advanced lung cancer, periventricular metastases are rare. We report one case of diffuse subependymal periventricular metastases from small cell carcinoma of the lung.

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