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Conventional chemo-radiotherapy scheme used in locally advancednon-small cell lung cancer (NSCLC) only achieves a small local tumor control, which negatively affects the patient’s survival.Dose escalation strategies have already shown to increase local control and survival of patients but with an increased risk of radiation-induced toxicity. It is therefore necessary to restrict the escalation in the region where it is most needed. It has been shown that tumor regions with high FDG uptake in PET imaging appear to have a higher resistance to radiation and coincide with the locations of the most likely recurrence. Consequently, a selective dose escalation of these areas is a good compromise to increase local control while minimizing toxicity. Since November 2010, 13 patients with locally advanced NSCLC were treated by radiotherapy with a scheme of 62.5Gy in 5 weeks (25 fraction of 2.5Gy) with individualized dose escalation conducted by Simultaneous Integrated Boost, increasing the dose per fraction on volumes identified by FDG-PET while respecting the predefined organs at risk dose constraints. The results in terms of local control seem to be better to those in the literature. The progression-free survivalrate at 6 months, 1 year and 2 years was 92.3, 71.9% and 43.2 % respectively, with a mediane progression-free survival of 13.85 months. Increasing the dose resulted in a small increase in acutelow grade esophagitis from 12 to 32% without increasing those of grade 3 or greater and in an increase in grade 3 or greater dermatitis of 15% in comparison with the conventional treatment, which remains acceptable give the reversible nature of the complications. Concerning late toxicity, the current results are comparable to conventional radiotherapy.The results obtained at this stage of the study are promising and recruitment must be continued in order to obtain statistically significant results. Le schéma conventionnel de radiothérapie utilisé dans le cancer pulmonaire non à petites cellules (NSCLC) localement avancé, associé le plus souvent avec la chimiothérapie, ne permet d'atteindre qu'un contrôle tumoral local relativement faible, ce qui influe négativement sur la survie des patients. Des stratégies d'intensification homogène de la dose ont déjà montré qu'elles augmentaient le contrôle local et le taux de survie des patients avec cependant une augmentation des risques de toxicité radio-induite. Il convient donc de restreindre l'escalade à la région qui en a le plus besoin. Il y a déjà été montré que les régions de la tumeur fixant avidement le traceur FDG au PET semblent présenter une radiorésistance supérieure aux autres zones et coïncident avec les endroits de récidive les plus probables. L'escalade de dose sélective ciblée sur ces régions tumorales est donc un bon compromis pour augmenter le contrôle local tout en limitant la toxicité. Depuis novembre 2010, 13 patients atteints d'un NSCLC localement avancé ont bénéficié d'un schéma de radiothérapie de 62.5 Gy en 5 semaines (25 fraction de 2.5 Gy) avec une escalade de dose réalisée simultanément en augmentant individuellement la dose par fraction sur les volumes identifiés par le FDG-PET par Simultaneous Integrated Boost, tout en respectant les contraintes de doses maximales prédéfinies pour les organes à risque. Les résultats obtenus en termes de contrôle local semblent supérieurs à ceux de la littérature. Le taux de survie sans progression locale à 6 mois, à un an et 2 ans est de 92,3, 71,9 % et 43,2 % respectivement, avec une médiane de survie sans progression locale de 13.85 mois. L'augmentation de la dose s'est traduite en aigu par une légère augmentation des oesophagites de faible grade de 12 à 32 % sans augmentation de celles de grade 3 ou plus et une augmentation des dermites de grade 3 ou plus de 15% par rapport au traitement conventionnel, ce qui reste acceptable étant donné le caractère réversible de ces complications. En toxicité tardive, les résultats actuels sont comparables au traitement conventionnel. Les résultats obtenus à ce stade de l'étude sont prometteurs et le recrutement doit donc être poursuivi afin de pouvoir obtenir des résultats statistiquement significatifs.

Small Cell Lung Carcinoma --- Bronchial Neoplasms --- Tomography, Emission-Computed

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Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC presents updated information on how EGFR mutant lung cancers evolve to evade EGFR inhibitors, clinical strategies that identify these mechanisms, and how to implement newer therapeutic strategies to combat resistance and improve patient survival. As resistance to EGFR inhibitors is often through re-activation of MEK/ERK and PI3K pathways, or through loss of cell death responses, there is much overlap with resistance to targeted therapies in other paradigms, such as BRAF inhibitors in BRAF mutant melanoma, and HER2 inhibitors in HER2 amplified breast cancer.

Antineoplastic Agents. --- Carcinoma, Non-Small-Cell Lung. --- Genes, erbB-1. --- Anticancer Agents --- Antineoplastic Drugs --- Antineoplastics --- Antitumor Agents --- Antitumor Drugs --- Cancer Chemotherapy Agents --- Cancer Chemotherapy Drugs --- Chemotherapeutic Anticancer Agents --- Chemotherapeutic Anticancer Drug --- Anticancer Agent --- Antineoplastic --- Antineoplastic Agent --- Antineoplastic Drug --- Antitumor Agent --- Antitumor Drug --- Cancer Chemotherapy Agent --- Cancer Chemotherapy Drug --- Agent, Anticancer --- Agent, Antineoplastic --- Agent, Antitumor --- Agent, Cancer Chemotherapy --- Agents, Anticancer --- Agents, Antineoplastic --- Agents, Antitumor --- Agents, Cancer Chemotherapy --- Agents, Chemotherapeutic Anticancer --- Chemotherapy Agent, Cancer --- Chemotherapy Agents, Cancer --- Chemotherapy Drug, Cancer --- Chemotherapy Drugs, Cancer --- Drug, Antineoplastic --- Drug, Antitumor --- Drug, Cancer Chemotherapy --- Drug, Chemotherapeutic Anticancer --- Drugs, Antineoplastic --- Drugs, Antitumor --- Drugs, Cancer Chemotherapy --- Cytotoxins --- Interferon Inducers --- Anticarcinogenic Agents --- Genes, erbB1 --- c-erbB-1 Proto-Oncogenes --- v-erbB Oncogenes --- EGFR Genes --- Epidermal Growth Factor Receptor Genes --- Genes, EGFR --- c-erbB-1 Genes --- erbB-1 Genes --- v-erbB Genes --- EGFR Gene --- Gene, erbB1 --- c erbB 1 Genes --- c erbB 1 Proto Oncogenes --- c-erbB-1 Gene --- c-erbB-1 Proto-Oncogene --- erbB 1 Genes --- erbB-1 Gene --- erbB1 Gene --- erbB1 Genes --- v erbB Genes --- v erbB Oncogenes --- v-erbB Gene --- v-erbB Oncogene --- Nonsmall Cell Lung Cancer --- Carcinoma, Non-Small Cell Lung --- Non-Small Cell Lung Cancer --- Non-Small Cell Lung Carcinoma --- Non-Small-Cell Lung Carcinoma --- Carcinoma, Non Small Cell Lung --- Carcinomas, Non-Small-Cell Lung --- Lung Carcinoma, Non-Small-Cell --- Lung Carcinomas, Non-Small-Cell --- Non Small Cell Lung Carcinoma --- Non-Small-Cell Lung Carcinomas --- Lung Neoplasms --- Carcinoma, Small Cell --- Drug resistance. --- Lungs --- Cancer --- Chemotherapy. --- Resistance to drugs --- Pharmacology --- ErbB Receptors --- Drug Resistance

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This Special Issue is dedicated to neuroendocrine neoplasms (NENs), a category of malignancy that demonstrates wide clinical heterogeneity, posing major challenges in diagnosis and management. There have been significant advances in the field of NEN genomics, pathology, imaging, and treatment over the past five years. NENs are examples of rare tumours (although their incidence and prevalence are increasing) where international collaborative efforts have allowed the generation of high-level evidence to guide optimal patient-centred care. This issue presents both reviews and original papers to provide comprehensive state-of-the-art understanding of this fascinating disease.

small bowel neuroendocrine tumours --- pancreatic neuroendocrine tumours --- liver metastases --- midgut --- meta-analysis --- neuroendocrine tumors --- carcinoid heart disease --- carcinoid syndrome --- somatostatin analogues --- metastases --- multidisciplinary --- management --- outcome --- grading --- staging --- neuroendocrine neoplasms --- chemotherapy --- temozolomide --- metronomic treatment --- second-line --- NOTCH --- cancer-driven genes --- mutational mechanism --- germline mutations --- small cell lung carcinoma --- pancreatic NET --- small bowel NET --- medullary thyroid carcinoma --- malignant castration-resistant prostatic cells --- quality performance indicators --- QPIs --- cancer care --- neuroendocrine tumour --- NETs --- modified Delphi --- CommNETs --- pancreatic neuroendocrine neoplasms --- neuroendocrine tumor --- long-term functional outcomes --- pancreatectomy --- diabetes mellitus --- pancreatic exocrine insufficiency --- body mass index --- parenchyma-sparing surgery --- neuroendocrine tumours --- curative surgery --- resection --- follow-up --- guidelines --- relapse --- recurrence --- risk factor --- mixed non-neuroendocrine neuroendocrine neoplasms --- MiNENs --- mixed adeno-neuroendocrine carcinoma --- MANEC --- 2017 WHO classification --- 2019 WHO classification

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The very first marine-derived anticancer drug, Cytarabine (aka Ara-C, Cytosar-U®), was approved by the FDA in 1969 for the treatment of leukemia. At the beginning of 2021, the list of approved marine-derived anticancer drugs consists of nine substances, five of which received approval within the last two years, demonstrating the rapid evolution of the field. The current book is a collection of scientific articles related to the exponentially growing field of anticancer marine compounds. These articles cover the whole field, from agents with cancer-preventive activity, to novel and previously characterized compounds with anticancer activity, both in vitro and in vivo, as well as the latest status of compounds under clinical development.

Medicine --- apoptosis --- fucoidan --- hepatocellular carcinoma --- reactive oxygen species --- 3-alkylpyridinium polymers --- nicotine --- nicotinic acetylcholine receptor --- non-small cell lung carcinoma --- melanoma --- sinulariolide --- proteomic --- mitochondria --- caspase cascade --- marine fungus --- sediment --- anthranilic acid --- Penicillium paneum --- cytotoxicity --- dibromotyrosine --- mitochondrial dysfunction --- oxidative stress --- topoisomerase --- epigonal organ --- bonnethead shark --- Jurkat --- tumor cell line --- hippuristanol --- PEL --- AP-1 --- STAT3 --- Akt --- colorectal cancer --- marine mollusc --- brominated indoles --- shrimp --- chemoprevention --- fatty acids --- carotenoids --- cancer --- nanoparticle --- osteosarcoma --- lung metastasis --- elisidepsin --- lipid rafts --- hydroxylated lipids --- fatty acid 2-hydroxylase --- cooperative binding --- membrane permeabilization --- marine organisms --- polysaccharides --- anticancer --- anticarcinogenic --- mechanisms of action --- fumigaclavine C --- anti-proliferation --- mitochondrial pathway --- anti-cancer --- anti-proliferative --- carotenoid --- cell cycle arrest --- fucoxanthin --- azoxymethane --- bioactive natural product --- isatin --- in vivo model --- Marthasterias glacialis L. --- palmitic acid --- ER-stress --- CHOP --- Antibody Drug Conjugates (ADCs) --- marine antitumor agents --- clinical trials --- approved antitumor agents --- AD0157 --- angiogenesis --- marine drug --- pyrrolidinedione --- secondary metabolites --- cancer preventive --- chemopreventive --- trabectedin --- plitidepsin --- tumor-associated macrophages --- tumor microenvironment --- preclinical --- anticancer immunity --- antiangiogenesis --- fascaplysin --- cyclin-dependent kinase --- small cell lung cancer --- camptothecin --- poly(ADP-ribose)-polymerase inhibitor --- breast cancer --- seaweed --- therapeutic compounds --- autophagy --- marine drugs --- autophagy inhibitors --- autophagy inducers --- macrolide --- programmed cell death --- energy stress --- araguspongine C --- c-Met --- HER2 --- gemcitabine --- pazopanib --- phase I --- safety --- soft tissue sarcoma --- pachastrissamine --- jaspine B --- carbocyclic analogue --- sphingosine kinase inhibitor --- molecular modeling --- ET-743 --- DNA minor groove binder --- soft tissue sarcoma --- chemotherapy --- bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) --- anti-metastatic activity --- cell adhesion --- β1-integrin --- FAK --- BEL-7402 cell --- triterpene glycosides --- sea cucumbers --- antitumor activities --- arrest of cell cycle --- antibacterial --- marangucyclines --- deep-sea --- Streptomyces sp. SCSIO 11594 --- LS-1 --- SNU-C5/5-FU --- TGF-β signaling --- carcinoembryonic antigen --- kalkitoxin --- Moorea producens --- mitochondria toxin --- VEGF --- angiogenesis inhibitor --- hypoxia-inducible factor-1 --- HIF-1 --- Lyngbya majuscula --- marine metabolites --- SZ-685C --- nonfunctioning pituitary adenomas --- Ecklonia cava --- phlorotannins --- dieckol --- migration --- sipholenol A --- ABC transporter --- multidrug resistance --- P-gp/ABCB1 --- BCRP/ABCG2 --- MRP1/ABCC1 --- marine natural products --- glioblastoma --- xyloketal B --- proliferation --- TRPM7 --- marine compound --- ribosomal protein genes --- snoRNA --- FAU --- RPS30 --- SNORA62 --- evolution --- Porifera --- Penicillium brevicompactum --- Brevianamide --- Mycochromenic acid derivative --- antifouling --- Caribbean sponge --- plakortide --- endoperoxide --- leukemia --- multi-drug resistant leukemia --- Sarcophyton ehrenbergi --- soft coral --- terpenes --- cembranoids --- cytotoxic activity --- molecular docking --- uveal melanoma --- oxidative stress --- virtual screening --- Topo I inhibitor --- low toxic --- natural product --- Ulva fasciata --- selenium-containing polysaccharide-protein complex --- pseudopterosin --- NF-κB --- p65 --- inflammation --- cytokine release --- IL-6 --- TNFα --- MCP-1 --- glucocorticoid receptor --- paulomycins --- Micromonospora --- antitumor --- Cantabrian Sea-derived actinobacteria --- puupehenones --- sponges --- antiangiogenic --- antitumoral --- porifera/sponge --- cancer genes --- molecular oncology --- bromophenol --- molecular mechanisms --- cell cycle --- PI3K/Akt --- p38/ERK --- ROS --- human lung cancer --- glycosaminoglycans --- antiproliferative --- heparan sulphate --- gliotoxin --- NSCLC --- adriamycin resistance --- Sepia ink polysaccharides --- antitumour --- chemosensitization --- anticoagulation --- sea anemone --- drug discovery --- endothelial cells --- RGD motif --- kunitz type inhibitor --- prostate cancer --- antioxidant --- natural marine compounds --- marine biotechnology --- microalgae --- marine sponges --- Aeroplysinin --- Isofistularin --- pheochromocytoma and paraganglioma --- metastasis --- cancer progression --- cell adhesion molecules --- integrin β1 --- hypoxia --- phycocyanin --- non-small cell lung cancer --- NF-κB signaling --- marine-derived drugs --- bioanalysis --- chromatography --- manzamine A --- epithelial-mesenchymal transition --- lung cancer --- circulating tumor cells --- signal transduction --- cisplatin --- Lampetra morii --- buccal gland --- cystatin F --- anti-angiogenesis --- cystatin superfamily --- Antimicrobial peptide (AMP) --- Tilapia piscidin 4 (TP4) --- non-small cell lung cancer (NSCLC) --- itampolin A --- FBDD --- p38α --- novel inhibitor --- tetracenomycin X --- cyclin D1 --- proteasomal degradation --- p38 --- c-JUN --- λ-carrageenan --- heparanase --- anticoagulant --- depolymerisation --- cell migration --- Aspergillus --- naphthopyrones --- endophytic fungus --- Leathesia nana --- mangrove-derived actinomycete --- ansamycins --- divergolides --- apoptosis-inducing activity --- actinomycin --- EMT --- invasion --- low molecular weight fucoidan extract --- N-Ras --- neuroblastoma-rat sarcoma --- Cancer --- programmed cell death-ligand 1 --- programmed cell death-ligand 2 --- human sarcoma cell line (HT1080 cells) --- human normal diploid fibroblast (TIG-1 cells) --- chimera --- chemical conjugation --- anticancer agent --- hybridization --- α9-nicotinic acetylcholine receptors (nAChRs) --- breast cancer cells --- αO-conotoxin GeXIVA --- targeted therapy --- gorgonian --- Leptogorgia --- humulane sesquiterpenoids --- anticancer activity --- 12-deacetyl-12-epi-scalaradial --- HeLa cells --- Nur77 --- MAPK/ERK pathway --- Mycalin A --- C15 acetogenins --- synthetic analogues --- antiproliferative activity --- A375 and HeLa cell lines --- polyoxygenated steroids --- sponge --- Haliclona gracilis --- Thalassia testudinum --- thalassiolin B --- polyphenols --- CYP1A1 --- benzo[a]pyrene --- JNK1/2 --- natural products --- synergism --- A549 cells --- cytoskeleton --- P2X7 receptor --- pollution --- anti-angiogenic --- gene expression --- HSP90 --- inhibitor --- apoptosis --- fucoidan --- hepatocellular carcinoma --- reactive oxygen species --- 3-alkylpyridinium polymers --- nicotine --- nicotinic acetylcholine receptor --- non-small cell lung carcinoma --- melanoma --- sinulariolide --- proteomic --- mitochondria --- caspase cascade --- marine fungus --- sediment --- anthranilic acid --- Penicillium paneum --- cytotoxicity --- dibromotyrosine --- mitochondrial dysfunction --- oxidative stress --- topoisomerase --- epigonal organ --- bonnethead shark --- Jurkat --- tumor cell line --- hippuristanol --- PEL --- AP-1 --- STAT3 --- Akt --- colorectal cancer --- marine mollusc --- brominated indoles --- shrimp --- chemoprevention --- fatty acids --- carotenoids --- cancer --- nanoparticle --- osteosarcoma --- lung metastasis --- elisidepsin --- lipid rafts --- hydroxylated lipids --- fatty acid 2-hydroxylase --- cooperative binding --- membrane permeabilization --- marine organisms --- polysaccharides --- anticancer --- anticarcinogenic --- mechanisms of action --- fumigaclavine C --- anti-proliferation --- mitochondrial pathway --- anti-cancer --- anti-proliferative --- carotenoid --- cell cycle arrest --- fucoxanthin --- azoxymethane --- bioactive natural product --- isatin --- in vivo model --- Marthasterias glacialis L. --- palmitic acid --- ER-stress --- CHOP --- Antibody Drug Conjugates (ADCs) --- marine antitumor agents --- clinical trials --- approved antitumor agents --- AD0157 --- angiogenesis --- marine drug --- pyrrolidinedione --- secondary metabolites --- cancer preventive --- chemopreventive --- trabectedin --- plitidepsin --- tumor-associated macrophages --- tumor microenvironment --- preclinical --- anticancer immunity --- antiangiogenesis --- fascaplysin --- cyclin-dependent kinase --- small cell lung cancer --- camptothecin --- poly(ADP-ribose)-polymerase inhibitor --- breast cancer --- seaweed --- therapeutic compounds --- autophagy --- marine drugs --- autophagy inhibitors --- autophagy inducers --- macrolide --- programmed cell death --- energy stress --- araguspongine C --- c-Met --- HER2 --- gemcitabine --- pazopanib --- phase I --- safety --- soft tissue sarcoma --- pachastrissamine --- jaspine B --- carbocyclic analogue --- sphingosine kinase inhibitor --- molecular modeling --- ET-743 --- DNA minor groove binder --- soft tissue sarcoma --- chemotherapy --- bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) --- anti-metastatic activity --- cell adhesion --- β1-integrin --- FAK --- BEL-7402 cell --- triterpene glycosides --- sea cucumbers --- antitumor activities --- arrest of cell cycle --- antibacterial --- marangucyclines --- deep-sea --- Streptomyces sp. SCSIO 11594 --- LS-1 --- SNU-C5/5-FU --- TGF-β signaling --- carcinoembryonic antigen --- kalkitoxin --- Moorea producens --- mitochondria toxin --- VEGF --- angiogenesis inhibitor --- hypoxia-inducible factor-1 --- HIF-1 --- Lyngbya majuscula --- marine metabolites --- SZ-685C --- nonfunctioning pituitary adenomas --- Ecklonia cava --- phlorotannins --- dieckol --- migration --- sipholenol A --- ABC transporter --- multidrug resistance --- P-gp/ABCB1 --- BCRP/ABCG2 --- MRP1/ABCC1 --- marine natural products --- glioblastoma --- xyloketal B --- proliferation --- TRPM7 --- marine compound --- ribosomal protein genes --- snoRNA --- FAU --- RPS30 --- SNORA62 --- evolution --- Porifera --- Penicillium brevicompactum --- Brevianamide --- Mycochromenic acid derivative --- antifouling --- Caribbean sponge --- plakortide --- endoperoxide --- leukemia --- multi-drug resistant leukemia --- Sarcophyton ehrenbergi --- soft coral --- terpenes --- cembranoids --- cytotoxic activity --- molecular docking --- uveal melanoma --- oxidative stress --- virtual screening --- Topo I inhibitor --- low toxic --- natural product --- Ulva fasciata --- selenium-containing polysaccharide-protein complex --- pseudopterosin --- NF-κB --- p65 --- inflammation --- cytokine release --- IL-6 --- TNFα --- MCP-1 --- glucocorticoid receptor --- paulomycins --- Micromonospora --- antitumor --- Cantabrian Sea-derived actinobacteria --- puupehenones --- sponges --- antiangiogenic --- antitumoral --- porifera/sponge --- cancer genes --- molecular oncology --- bromophenol --- molecular mechanisms --- cell cycle --- PI3K/Akt --- p38/ERK --- ROS --- human lung cancer --- glycosaminoglycans --- antiproliferative --- heparan sulphate --- gliotoxin --- NSCLC --- adriamycin resistance --- Sepia ink polysaccharides --- antitumour --- chemosensitization --- anticoagulation --- sea anemone --- drug discovery --- endothelial cells --- RGD motif --- kunitz type inhibitor --- prostate cancer --- antioxidant --- natural marine compounds --- marine biotechnology --- microalgae --- marine sponges --- Aeroplysinin --- Isofistularin --- pheochromocytoma and paraganglioma --- metastasis --- cancer progression --- cell adhesion molecules --- integrin β1 --- hypoxia --- phycocyanin --- non-small cell lung cancer --- NF-κB signaling --- marine-derived drugs --- bioanalysis --- chromatography --- manzamine A --- epithelial-mesenchymal transition --- lung cancer --- circulating tumor cells --- signal transduction --- cisplatin --- Lampetra morii --- buccal gland --- cystatin F --- anti-angiogenesis --- cystatin superfamily --- Antimicrobial peptide (AMP) --- Tilapia piscidin 4 (TP4) --- non-small cell lung cancer (NSCLC) --- itampolin A --- FBDD --- p38α --- novel inhibitor --- tetracenomycin X --- cyclin D1 --- proteasomal degradation --- p38 --- c-JUN --- λ-carrageenan --- heparanase --- anticoagulant --- depolymerisation --- cell migration --- Aspergillus --- naphthopyrones --- endophytic fungus --- Leathesia nana --- mangrove-derived actinomycete --- ansamycins --- divergolides --- apoptosis-inducing activity --- actinomycin --- EMT --- invasion --- low molecular weight fucoidan extract --- N-Ras --- neuroblastoma-rat sarcoma --- Cancer --- programmed cell death-ligand 1 --- programmed cell death-ligand 2 --- human sarcoma cell line (HT1080 cells) --- human normal diploid fibroblast (TIG-1 cells) --- chimera --- chemical conjugation --- anticancer agent --- hybridization --- α9-nicotinic acetylcholine receptors (nAChRs) --- breast cancer cells --- αO-conotoxin GeXIVA --- targeted therapy --- gorgonian --- Leptogorgia --- humulane sesquiterpenoids --- anticancer activity --- 12-deacetyl-12-epi-scalaradial --- HeLa cells --- Nur77 --- MAPK/ERK pathway --- Mycalin A --- C15 acetogenins --- synthetic analogues --- antiproliferative activity --- A375 and HeLa cell lines --- polyoxygenated steroids --- sponge --- Haliclona gracilis --- Thalassia testudinum --- thalassiolin B --- polyphenols --- CYP1A1 --- benzo[a]pyrene --- JNK1/2 --- natural products --- synergism --- A549 cells --- cytoskeleton --- P2X7 receptor --- pollution --- anti-angiogenic --- gene expression --- HSP90 --- inhibitor