Prolactin as a possible predictive factor in metastatic non-small cell lung cancers (NSCLC) patients in treatment with Nivolumab (NIVO)

Abstract Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major histological categories of lung cancers. Drug resistance is a great challenge for cancer treatment, and histological transformation from NSCLC to SCLC is one of the mechanisms underlying drug resistance in NSCLC patients. SCLC-transformed patients show combined characteristics of NSCLC and SCLC; however, they lack timely diagnoses and effective treatment strategies. Thus, we reviewed the clinical characteristics of SCLC transformation patients with a literature search to enhance clinical consciousness, diagnosis, and personalized treatment for patients with it.

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Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer

Nature Communications ◽

10.1038/s41467-021-27303-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Clemens Hinterleitner ◽

Jasmin Strähle ◽

Elke Malenke ◽

Martina Hinterleitner ◽

Melanie Henning ◽

...

Keyword(s):

Lung Cancer ◽

Checkpoint Inhibitors ◽

Blood Platelets ◽

Therapy Response ◽

Small Cell ◽

Dependent Manner ◽

Small Cell Lung ◽

Tumor Immune Evasion ◽

Lung Cancers ◽

Nsclc Patients

AbstractImmune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner. Platelets from NSCLC patients are found to express PD-L1 and platelet PD-L1 possess the ability to inhibit CD4 and CD8 T-cells. An algorithm is developed to calculate the activation independent adjusted PD-L1 payload of platelets (pPD-L1Adj.), which is found to be superior in predicting the response towards ICI as compared to standard histological PD-L1 quantification on tumor biopsies. Our data suggest that platelet PD-L1 reflects the collective tumor PD-L1 expression, plays important roles in tumor immune evasion and overcomes limitations of histological quantification of often heterogeneous intratumoral PD-L1 expression.

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Threshold Effects of Plasma Methyl Donor Nutrients Status on High Lactate-Metabolomics Signatures of Metastatic Tumors in Non-Small-Cell Lung Cancer Patients

Current Developments in Nutrition ◽

10.1093/cdn/nzaa044_011 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 312-312

Author(s):

Yen-Chu Chen ◽

Jin-Shing Chen ◽

Mei-Ling Cheng ◽

Rwei-Fen Syu Huang

Keyword(s):

Lung Cancer ◽

Small Cell ◽

Lactate Metabolism ◽

Small Cell Lung ◽

Lung Cancers ◽

Methyl Donors ◽

Metastatic Nsclc ◽

Free Choline ◽

Nsclc Patients ◽

High Lactate

Abstract Objectives Lung cancer is the leading cause of cancer-related mortality in the worldwide. In non-small-cell lung cancers (NSCLC), metabolic reprogramming of lactate metabolism has been proposed as a key player in cancer metastasis. Nutritional status of methyl donors was associated with increased risks of lung cancers, yet their roles in lactate metabolism and metastatic NSCLC development remains unclear. Methods The cross-sectional study recruited 100 NSCLC patients with selected 18 paired NSCLC tissues from National Taiwan University Hospital (NTUH), Taiwan. Plasma methyl donors levels (folate/free choline/betaine) of NSCLC patients and target metabolomics signatures of paired NSCLC tissues were analyzed by Liquid chromatography–mass spectrometry (LC/MS). Clinical data of NSCLC tissues were collected from the department of pathology in NTUH. Results Partial Least Squares Discriminant Analysis (PLSDA) revealed that metabolic signatures of tumor/non-tumor lung tissues were well segregated. The two major tumor metabolites signatures of metastatic NSCLC were lactate and glucose, the levels of which were high and low, respectively, with both metabolites displaying the two highest VIP scores. A correlation heatmap showed that tumor lactate levels were strongly associated with increased TCA metabolites (pyruvate, succinate, fumarate and malate) and anaplerotic amino acid levels (alanine and arginine), and inversely correlated with glycolytic metabolites (glucose and PEP). When stratifying plasma methyl donors status of 18 paired NSCLC tumors with metabolomics VIP scores, threshold levels of folate (≥6 ng/ml), free choline (≥9.78 µmol/L) and betaine (≥62.0 µmol/L) were associated with high lactate and low glucose signatures of NSCLC. In particular, plasma betaine was positively associated with tumor lactate (r = 0.51, P = 0.031); plasma lactate was positively associated with tumor glucose (r = 0.53, P = 0.023). Conclusions Our data demonstrate that metastatic NSCLCs were signified with high-lactate metabolizing-metabolomics fingerprints which were modified by plasma methyl donors’ status with a differential threshold effect. Funding Sources This study was supported by the three-year grant from the Ministration of Science and Technology, Taiwan, ROC.

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Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer

Journal of Oncology ◽

10.1155/2013/240164 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Raul Storey ◽

Joongho Joh ◽

Amy Kwon ◽

A. Bennett Jenson ◽

Shin-je Ghim ◽

...

Keyword(s):

Human Papillomavirus ◽

Small Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Small Cell Lung ◽

Hpv 16 ◽

Lung Cancers ◽

Hpv Dna ◽

The One ◽

Nsclc Patients ◽

Hpv 18

Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV’s possible etiologic link to NSCLC by evaluating an immune response to HPV’s oncogene, E7, in patients with NSCLC.Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA).Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive.Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC.

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Conditional Survival Probability of Non-Small Cell Lung Cancers, Based on The SEER Database

10.21203/rs.3.rs-138915/v1 ◽

2021 ◽

Author(s):

Shixu Fang ◽

Kui Zhai ◽

Xixian Ke ◽

Hao Han ◽

Hongling Lu ◽

...

Keyword(s):

Survival Probability ◽

Tnm Staging ◽

Small Cell ◽

Cancer Prognosis ◽

Conditional Survival ◽

Seer Database ◽

Small Cell Lung ◽

Lung Cancers ◽

Nsclc Patients ◽

Over Time

Abstract Background: This study aims to explore the dynamic survival probability of lung cancers after resection based on those had survived several years, provide more precise monitoring and treatment information for non-metastatic non-small cell lung cancer (NSCLC) patients.Materials and Methods: In the Surveillance, Epidemiology, and End Results (SEER) database (2000–2016), 95531 eligible non-metastatic NSCLC patients after surgery were enrolled, TNM stage were reclassified, the methods of condition survival probability (CS) and actuarial overall survival (OS) were used to explore the relationship between clinicopathological characteristics and cancer prognosis.Results: The 1-, 3-, 5- and 10-year OS of included patients were 83.6% (95%CI: 83%-84%), 62.9% (95%CI: 62.6%-63.1%), 50.8% (95%CI: 50.6%-51.0%) and 33.1% (95%CI: 32.7%-33.6%) respectively. For those already survived 1, 2, 3, 4 and 5 years after diagnosis, the probability for surviving an additional 3 years were 67%, 71%, 73%, 75% and 77% respectively. Enrolled population were reclassified into 9 cohorts including T1aN0, T1bN0, T1cN0, T2aN0, T2bN0, T3N0, T4N0, T1-4N1, T1-4N2 according to 8th TNM staging. According to the conditional survival probability, patients with unfavorable tumor stage diagnosed initially at surgery had the significant improvement in CS over time. Analysis based on other clinical features demonstrated similar conclusion that the poorer the initial diagnosis, the more significant the benefit of conditional survival over time.Conclusion: The worse the patient's prognosis, the more significant the benefit of time-dependent conditional survival probability, long-lived cancer patients may have a better cancer prognosis.

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Real-world large-scale study of ERBB2 gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13002 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13002-e13002

Author(s):

Chunwei Xu ◽

Wen xian Wang ◽

Quxia Zhang ◽

Yu Chen ◽

Xiuyu Cai ◽

...

Keyword(s):

Multicenter Study ◽

Large Scale ◽

Index Patient ◽

Small Cell ◽

Driver Gene ◽

Small Cell Lung ◽

Lung Cancers ◽

Case Examples ◽

Entire Cohort ◽

Nsclc Patients

e13002 Background: ERBB2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers (NSCLC) and ERBB2-directed therapies have shown promising results in this unique population, while little is known about ERBB2 fusion association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced ERBB2 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the ERBB2 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, eight (0.29%) patients were identified with an ERBB2 fusion, including TNS4-ERBB2 (1), ERBB2-CD79B (1), IGFBP4-ERBB2 (1), ERBB2-PSMD3 (1), SEZ6-ERBB2 (1), ERBB2-PGAP3 (1), ARL5C-ERBB2 (1) and B3GNTL1-ERBB2 (1). The genes most frequently co-altered in patients with ERBB2 fusions were TP53 (37.50%), CDKN2A (25.00%), RB1 (25.00%) and RBM10 (25.00%). Overall TMB in the ERBB2 fusions was low (median 2.97 mut/Mb). For treatments, 25.00% patients chose afatinib, another patients chose chemotherapy or chemoradiotherapy, and case examples of advanced ERBB2 fusion driven NSCLC patients responding to afatinib were actively being sought thru our database. Conclusions: Patients with advanced ERBB2 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ ROS1 fusion which response to crizotinib, which strengthen the need for effective ERBB2-targeted drugs in clinical practice.

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Specific Adverse Effects of Bevacizumab in the Treatment of Non-Squamous Non-Small Cell Lung Cancer (NSCLC) in Clinical Practice

Revista de Chimie ◽

10.37358/rc.18.12.6810 ◽

2019 ◽

Vol 69 (12) ◽

pp. 3644-3647

Author(s):

Laura Mazilu ◽

Dana Lucia Stanculeanu ◽

Andreea Daniela Gheorghe ◽

Adrian Paul Suceveanu ◽

Razvan Hainarosie ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Invasion And Metastasis ◽

Small Cell Lung ◽

Lung Cancers ◽

Complex Process ◽

Nsclc Patients ◽

Related Mortality

Lung cancer is the most common cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) represents about 85% of all lung cancers. In the last years, novel targeted therapies have been developed and approved in the treatment of NSCLC. Angiogenesis is a very complex process, and cancer angiogenesis is the most important event concerning cancer growth, invasion and metastasis. VEGF signalling pathway plays a significant role in cancer angiogenesis, and it is demonstrated that VEGF levels are correlated with increased angiogenesis and with poor prognosis and metastasis in NSCLC patients. Bevacizumab is a recombinant humanised monoclonal IgG1 antibody, it is one of the first agent used for anti-angiogenic treatment, and it was approved for the treatment of non-squamous NSCLC in combination with chemotherapy.

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Calpeptin Induces Apoptosis in A549 Non-Small Cell Lung Cancer Cells

10.21203/rs.3.rs-947991/v1 ◽

2021 ◽

Author(s):

Chiharu Tabata ◽

Rie Tabata

Keyword(s):

Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Calpain Inhibitor ◽

Small Cell Lung ◽

Lung Cancers ◽

Novel Treatments ◽

Stage Disease ◽

Induced Apoptosis ◽

Nsclc Patients

Abstract Lung cancer is a leading cause of cancer-related death worldwide, and most are non-small cell lung cancers (NSCLC). Since the overall survival remains very poor for NSCLC patients with advanced-stage disease, the development of novel treatments is needed. Previous studies reported a relationship between calpain and tumorigenesis. In this study, we examined the apoptotic effects of calpeptin (Cal), a calpain inhibitor, on A549 NSCLC cells. We assessed whether Cal induced apoptosis in A549 cells. Cal induced apoptosis in A549 cells and also activated p38MAPK. These results suggest a possible clinical use of Cal for the treatment of NSCLC.

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BMI1-Mediated Pemetrexed Resistance in Non-Small Cell Lung Cancer Cells Is Associated with Increased SP1 Activation and Cancer Stemness

Cancers ◽

10.3390/cancers12082069 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2069

Author(s):

Huan-Ting Shen ◽

Peng-Ju Chien ◽

Shih-Hong Chen ◽

Gwo-Tarng Sheu ◽

Ming-Shiou Jan ◽

...

Keyword(s):

Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung ◽

Ki 67 ◽

Lung Cancers ◽

Mesenchymal Transition ◽

Bmi1 Expression ◽

Nsclc Patients

Lung cancer is the leading cause of cancer death worldwide and the therapeutic strategies include surgery, chemotherapy and radiation therapy. Non-small cell lung cancers (NSCLCs) account for around 85% of cases of lung cancers. Pemetrexed is an antifolate agent that is currently used as the second line chemotherapy drug in the treatment of advanced NSCLC patients with a response rate of 20–40%. The search for any combination therapy to improve the efficacy of pemetrexed is required. The existence of cancer stem cells (CSCs) is considered as the main reason for drug resistance of cancers. In this study, we first found that pemetrexed-resistant NSCLC cells derived from A549 cells displayed higher CSC activity in comparison to the parental cells. The expression of CSC related proteins, such as BMI1 or CD44, and the epithelial–mesenchymal transition (EMT) signature was elevated in pemetrexed-resistant NSCLC cells. We next discovered that the overexpression of BMI1 in A549 cells caused the pemetrexed resistance and inhibition of BMI1 by a small molecule inhibitor, PTC-209, or transducing of BMI1-specific shRNAs suppressed cell growth and the expression of thymidylate synthase (TS) in pemetrexed-resistant A549 cells. We further identified that BMI1 positively regulated SP1 expression and treatment of mithramycin A, a SP1 inhibitor, inhibited cell proliferation, as well as TS expression, of pemetrexed-resistant A549 cells. Furthermore, overexpression of BMI1 in A549 cells also caused the activation of EMT in and the enhancement of CSC activity. Finally, we demonstrated that pretreatment of PTC-209 in mice bearing pemetrexed-resistant A549 tumors sensitized them to pemetrexed treatment and the expression of Ki-67, BMI1, and SP1 expression in tumor tissues was observed to be reduced. In conclusion, BMI1 expression level mediates pemetrexed sensitivity of NSCLC cells and the inhibition of BMI1 will be an effective strategy in NSCLC patients when pemetrexed resistance has developed.

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