Electronic and Geometric Effects Endow PtRh Jagged Nanowires with Superior Ethanol Oxidation Catalysis.

Complete ethanol oxidation reaction (EOR) in C1 pathway with 12 transferred electrons is highly desirable yet challenging in direct ethanol fuel cells. Herein, PtRh jagged nanowires synthesized via a simple wet-chemical approach exhibit exceptional EOR mass activity of 1.63 A mgPt-1 and specific activity of 4.07 mA cm-2 , 3.62-fold and 4.28-folds increments relative to Pt/C, respectively. High proportions of 69.33% and 73.42% of initial activity are also retained after chronoamperometric test (80 000 s) and 1500 consecutive potential cycles, respectively. More importantly, it is found that PtRh jagged nanowires possess superb anti-CO poisoning capability. Combining X-ray absorption spectroscopy, X-ray photoelectron spectroscopy as well as density functional theory calculations unveil that the remarkable catalytic activity and CO tolerance stem from both the Rh-induced electronic effect and geometric effect (manifested by shortened Pt─Pt bond length and shrinkage of lattice constants), which facilitates EOR catalysis in C1 pathway and improves reaction kinetics by reducing energy barriers of rate-determining steps (such as *CO → *COOH). The C1 pathway efficiency of PtRh jagged nanowires is further verified by the high intensity of CO2 relative to CH3 COOH/CH3 CHO in infrared reflection absorption spectroscopy.

Integration of multiple advantages into one catalyst: non-CO pathway of methanol oxidation electrocatalysis on surface Ir-modulated PtFeIr jagged nanowires.

Developing highly active methanol oxidation electrocatalysts with superior anti-CO poisoning capability remains a grand challenge. Herein, a simple strategy was employed to prepare distinctive PtFeIr jagged nanowires with Ir located at the shell and Pt/Fe located at the core. The Pt64Fe20Ir16 jagged nanowire possesses an optimal mass activity of 2.13 A mgPt-1 and specific activity of 4.25 mA cm-2, giving the catalyst a great edge over PtFe jagged nanowire (1.63 A mgPt-1 and 3.75 mA cm-2) and Pt/C (0.38 A mgPt-1 and 0.76 mA cm-2). The in-situ Fourier transform infrared (FTIR) spectroscopy and differential electrochemical mass spectrometry (DEMS) unravel the origin of extraordinary CO tolerance in terms of key reaction intermediates in the non-CO pathway. Density functional theory (DFT) calculations add to the body of evidence that the surface Ir incorporation transforms the selectivity from CO pathway to non-CO pathway. Meanwhile, the presence of Ir serves to optimize surface electronic structure with weakened CO binding strength. We believe this work will advance the understanding of methanol oxidation catalytic mechanism and provide some insight into structural design of efficient electrocatalysts.

siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes.

siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient myocardial enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing the Hippo pathway and inducing cardiomyocyte regeneration. The biomimetic BSPC@HM NCs consist of a cationic nanocore assembled from a membrane-penetrating helical polypeptide (P-Ben) and siSav1, a charge-reversal intermediate layer of poly(l-lysine)-cis-aconitic acid (PC), and an outer shell of HM. Due to HM-mediated inflammation homing and microthrombus targeting, intravenously injected BSPC@HM NCs can efficiently accumulate in the IR-injured myocardium, where the acidic inflammatory microenvironment triggers charge reversal of PC to shed off both HM and PC layers and allow the penetration of the exposed P-Ben/siSav1 NCs into cardiomyocytes. In rats and pigs, BSPC@HM NCs remarkably downregulates Sav1 in IR-injured myocardium, promotes myocardium regeneration, suppresses myocardial apoptosis, and recovers cardiac functions. This study reports a bioinspired strategy to overcome the multiple systemic barriers against myocardial siRNA delivery, and holds profound potential for gene therapy against cardiac injuries.

Inflammatory Cell-Inspired Cascade Nanozyme Induces Intracellular Radical Storm for Enhanced Anticancer Therapy.

Manipulating intracellular levels of reactive oxygen and nitrogen species (RONS) is of great potential for cancer treatment. Inspired by the natural mechanism of a radical storm in inflammatory cells via activated and regulatable biocatalysis, the authors herein report a self-powered nanozyme that can enable RONS production in tumor cells via cascade reactions. The nanozymes are constructed via glucose oxidase (GOx)-templated inverse microemulsion polymerization from acrylamide, arginine-acrylamide, ferrocene-acrylate, and N,N'-bis(acryloyl)cystamine, followed by surface coating with hyaluronic acid. After targeted delivery into cancer cells, the nanozymes are dissociated by intracellular glutathione to release GOx, which decomposed glucose to generate gluconic acid and H2 O2 . Under such acidified conditions, H2 O2 efficiently oxidized pendant arginine residues to produce nitric oxide , transformed into a highly toxic hydroxyl radical and superoxide anion via ferrocene-mediated Fenton reaction and Haber-Weiss cycle, and simultaneously generated peroxynitrite anion via reaction between NO and ·O2 - , thus provoking the RONS radical storm to effectively eradicate A549 tumor cells both in vitro and in vivo. This nature-inspired enzyme-chemical dynamic therapy may provide a promising modality for anti-cancer treatment.

Spherical α-helical polypeptide-mediated E2F1 silencing against myocardial ischemia-reperfusion injury (MIRI).

Apoptosis of cardiomyocytes is a critical outcome of myocardial ischemia-reperfusion injury (MIRI), which leads to the permanent impairment of cardiac function. Upregulated E2F1 is implicated in inducing cardiomyocyte apoptosis, and thus intervention of the E2F1 signaling pathway via RNA interference may hold promising potential for rescuing the myocardium from MIRI. To aid efficient E2F1 siRNA (siE2F1) delivery into cardiomyocytes that are normally hard to transfect, a spherical, α-helical polypeptide (SPP) with potent membrane activity was developed via dendrimer-initiated ring-opening polymerization of N-carboxyanhydride followed by side-chain functionalization with guanidines. Due to its multivalent structure, SPP outperformed its linear counterpart (LPP) to feature potent siRNA binding affinity and membrane activity. Thus, SPP effectively delivered siE2F1 into cardiomyocytes and suppressed E2F1 expression both in vitro and in vivo after intramyocardial injection. The E2F1-miR421-Pink1 signaling pathway was disrupted, thereby leading to the reduction of MIRI-induced mitochondrial damage, apoptosis, and inflammation of cardiomyocytes and ultimately recovering the systolic function of the myocardium. This study provides an example of membrane-penetrating nucleic acid delivery materials, and it also provides a promising approach for the genetic manipulation of cardiomyocyte apoptosis for the treatment of MIRI.

PtIrM (M = Ni, Co) jagged nanowires for efficient methanol oxidation electrocatalysis.

It remains a huge challenge to develop methanol oxidation electrocatalysts with remarkable catalytic activity and anti-CO poisoning capability. Herein, PtIrNi and PtIrCo jagged nanowires are successfully synthesized via a facile wet-chemical approach. Pt and Ir components are concentrated in the exterior and Ni is concentrated in the interior of PtIrNi jagged nanowires, while PtIrCo jagged nanowires feature the homogeneous distribution of constituent metals. The PtIrNi and PtIrCo jagged nanowires exhibit mass activities of 1.88 A/mgPt and 1.85 A/mgPt, respectively, 3.24 and 3.19 times higher than that of commercial Pt/C (0.58 A/mgPt). In-situ Fourier transform infrared spectroscopy indicates that CO2 was formed at a very low potential for both nanowires, in line with the high ratio of forward current density to backward current density for PtIrNi jagged nanowires (1.30) and PtIrCo jagged nanowires (1.46) relative to Pt/C (0.76). Also, the CO stripping and X-ray photoelectron spectroscopy results substantiate the remarkable CO tolerance of the jagged nanowires. Besides, the two jagged nanowires possess exceptional activities toward ethanol and ethylene glycol oxidation reactions. This work provides a novel line of thought in terms of rational design of alcohol oxidation electrocatalysts with distinctive nanostructures.

Platelet Pharmacytes for the Hierarchical Amplification of Antitumor Immunity in Response to Self-Generated Immune Signals.

Systemic immunosuppression mediated by tumor-derived exosomes is an important cause for the resistance of immune checkpoint blockade (ICB) therapy. Herein, self-adaptive platelet (PLT) pharmacytes are engineered to mediate cascaded delivery of exosome-inhibiting siRNA and anti-PD-L1 (aPDL1) toward synergized antitumor immunity. In the pharmacytes, polycationic nanocomplexes (NCs) assembled from Rab27 siRNA (siRab) and a membrane-penetrating polypeptide are encapsulated inside the open canalicular system of PLTs, and cytotoxic T lymphocytes (CTLs)-responsive aPDL1 nanogels (NGs) are covalently backpacked on the PLT surface. Upon systemic administration, the pharmacytes enable prolonged blood circulation and active accumulation to tumors, wherein PLTs are activated to liberate siRab NCs, which efficiently transfect tumor cells, silence Rab27a, and inhibit exosome secretion. The immunosuppression is thus relieved, leading to the activation, proliferation, and tumoral infiltration of cytotoxic T cells, which trigger latent aPDL1 release. As such, the competitive aPDL1 exhaustion by PD-L1-expressing exosomes is minimized to sensitize ICB. Synergistically, siRab and aPDL1 induce strong antitumor immunological response and memory against syngeneic murine melanoma. This study reports a bioinspired mechanism to resolve the blood circulation/cell internalization contradiction of polycationic siRNA delivery systems, and renders an enlightened approach for the spatiotemporal enhancement of antitumor immunity.

Cardiopulmonary bypass does not consequentially contribute to postoperative distant metastasis of giant refractory thoracic tumors: A retrospective study with long-term follow-up.

BACKGROUND: Few clinical research studies with long-term follow-up have revealed whether cardiopulmonary bypass (CPB) increases the risk of postoperative distant metastasis in patients with giant refractory thoracic tumors. The present study evaluated the risk of distant metastasis after surgery utilizing CPB with long-term follow-up. METHODS: Clinical data for patients with giant refractory thoracic tumors who underwent resection with the use of CPB in the Second Affiliated Hospital of Soochow University during the past 11 years were retrospectively reviewed. RESULTS: Of the 14 patients with giant refractory thoracic tumors who had undergone surgery under CPB, 10 patients (71.4%) were completely resected. Twelve patients were followed up for 13-127 months with 10 patients were completely resected and two patients could not be completely resected due to severe tissue invasion. Three patients (25%) suffered from distant metastasis, and four patients (33.3%) experienced local recurrence. Only one patient (1/10) with complete resection suffered from distant metastasis, while two patients (2/10) experienced local recurrence. Two patients (2/2) with major resection suffered from both distant metastasis and local recurrence. Median overall survival for patients who have been regularly followed up was 50 months with 1-, 5-, and 10-year survival of 100%, 75%, and 66.7%. No difference was found between the distant metastasis survival and the local recurrence survival. (p = 0.99). CONCLUSIONS: CPB is an effective strategy for complete resection of the giant refractory thoracic tumors with an acceptable risk of postoperative distant metastasis for some patients.

[Progress in Single-cell RNA Sequencing of Lung Adenocarcinoma].

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and one of the main causes of cancer-related deaths. In the past decade, with the widespread use of computed tomography (CT) in routine screening for lung cancer, the incidence of LUAD presenting as small pulmonary nodules radiologically, has increased remarkably. The mechanisms of the occurrence and progression of LUADs are complex, and the prognoses of patients with LUAD vary significantly. Although significant progress has been made in targeted therapy and immunotherapy for LUADs in recent years, the drug resistance of tumor cells has not been effectively overcome, which limits the benefits of patients. With the accomplishment of the Human Genome Project, sequencing-based genomic and transcriptomics have come into the field of clinical and scientific researches. Single-cell sequencing, as a new type of sequencing method that has captured increasing attention recently, can perform specific analysis of cell populations at single-cell level, which can reveal the unique changes of each cell type. Single-cell sequencing can also provide accurate assessment on heterogeneous stromal cells and cancer cells, which is helpful to reveal the complexity of molecular compositions and differences between non- and malignant tissues. To sum up, it is an urgent need for clinicians and basic scientists to deeply understand the pathogenesis and development of LUAD, the heterogeneity of tumor microenvironment (TME) and the mechanism of drug resistance formation through single-cell sequencing, so as to discover new therapeutic targets. In this paper, we reviewed and summarized the application and progress in single-cell sequencing of LUADs.
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Cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions.

Cytosolic protein delivery holds great potential for the development of protein-based biotechnologies and therapeutics. Currently, cytosolic protein delivery is mainly achieved with the assistance of various carriers. Herein, we present a universal and effective strategy for carrier-free cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions. Ac4ManNAz (AAM), an azido-modified N-acetylmannosamine analogue, was first employed to label tumor cell surfaces with abundant azido groups via glycometabolism. Then, proteins including RNase A, cytochrome C (Cyt C), and bovine serum albumin (BSA) were covalently modified with dibenzocyclooctyne (DBCO). Based on the highly efficient bioorthogonal click reactions between DBCO and azido, DBCO-modified proteins could be efficiently internalized by azido-labeled cancer cells. RNase A-DBCO could largely maintain its enzymatic activity and, thus, led to notable anti-tumor efficacy in HeLa and B16F10 cells in vitro and in B16F10 xenograft tumors in vivo. This study therefore provides a simple and powerful approach for carrier-free protein delivery and would have broad applicability in anti-tumor protein therapy.

[Corrigendum] Increased infiltration of macrophages to radioresistant lung cancer cells contributes to the development of the additional resistance of tumor cells to the cytotoxic effects of NK cells.

Subsequently to the publication of the above paper, the authors have realized that the western blots featured in Fig. 5B were inadvertently copied across from Fig. 4B owing to an error made during the figure compilation process. The corrected version of Fig. 5 is featured on the next page, showing the correct data for the western blot analysis of the programmed death receptor ligand 1 level in radioresistant lung cancer cells under the specified experimental conditions. Note that these changes do not affect the interpretation of the data or the conclusions reported in this paper, and all the authors agree to this correction. The authors apologize to the Editor and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 53: 317-328, 2018; DOI: 10.3892/ijo.2018.4394].

Bioreducible, branched poly(ß-amino ester)s mediate anti-inflammatory ICAM-1 siRNA delivery against myocardial ischemia reperfusion (IR) injury.

siRNA-mediated RNA interference (RNAi) against inflammation-related genes provides a promising modality for the treatment of myocardial ischemia reperfusion (IR) injury, and its success is critically dependent on the development of efficient yet safe siRNA delivery vehicles. Herein, we developed a bioreducible, branched poly(ß-amino ester) with built-in redox-responsive domains (BPAE-SS) for the effective ICAM-1 siRNA delivery into injured rat cardiac microvascular endothelial cells (RCMECs). The branched BPAE-SS with a multivalent structure afforded potent siRNA binding affinity compared to its linear analogue, while upon internalization into RCMECs it was instantaneously degraded by intracellular glutathione (GSH) into small segments to mediate "on-demand" siRNA release and diminish the toxicity of post-transfection materials. By synchronizingly overcoming these critical barriers, BPAE-SS mediated remarkable ICAM-1 knockdown in IR-injured rats at 400 µg siRNA per kg via single i.v. injection, and subsequently suppressed myocardial inflammation, apoptosis, and fibrosis to recover the cardiac function. This study therefore provides a unique delivery system that can address the multiple critical challenges against non-viral siRNA delivery, and the potent therapeutic efficacy of BPAE-SS-mediated ICAM-1 silencing provides a promising strategy for the anti-inflammatory treatment of myocardial IR injury.

Topology-assisted, photo-strengthened DNA/siRNA delivery mediated by branched poly(ß-amino ester)s via synchronized intracellular kinetics.

The performance of non-viral gene delivery vehicles, especially cationic polymers, is often challenged by the multiple cellular barriers that pose inconsistent requirements for material properties. A most pronounced inconsistency is exemplified by the molecular weight (MW)-related transfection efficiency and cytotoxicity. In this study, we report the development of photo-degradable, branched poly(ß-amino ester)s (BPAE-NB) to realize efficient and photo-controlled DNA and siRNA delivery. BPAE-NB possessing built-in light-responsive 2-nitrobenzene moieties in the polymer backbone was synthesized via the A2 (amine) + B3 (triacrylate) + C2 (diacrylate) polycondensation reaction from 4-amino-1-butanol (A2), trimethylolpropane triacrylate (B3), and (2-nitro-1,3-phenylene)bis(methylene) diacrylate (NPBMDA, C2). The highly branched BPAE-NB with the multivalent arrangement of cationic groups provides stronger nucleic acid binding capacity than its linear analogue LPAE-NB, and thus features stronger trans-membrane gene delivery capabilities and higher transfection efficiencies. Upon UV light irradiation, the backbone of BPAE-NB can quickly degrade into low-MW fragments as a consequence of the cleavage of the light-responsive 2-nitrobenzene, thus promoting intracellular gene release and diminishing the toxicity of materials at the post-transfection state. As such, in multiple mammalian cells, BPAE-NB exhibited remarkably higher DNA/siRNA transfection efficiency yet lower cytotoxicity than its non-responsive analogue BPAE-CC upon light irradiation, notably outperforming commercial reagents PEI 25k and Lipofectamine 2000. This study therefore provides an effective topology- and photo-controlled approach to precisely manipulate the transfection efficiency and toxicity of polycationic gene vectors, and may also provide promising additions to the existing non-viral gene delivery vectors.

Recent Advances on Reactive Oxygen Species-Responsive Delivery and Diagnosis System.

Reactive oxygen species (ROS) play crucial roles in biological metabolism and intercellular signaling. However, ROS level is dramatically elevated due to abnormal metabolism during multiple pathologies, including neurodegenerative diseases, diabetes, cancer, and premature aging. By taking advantage of the discrepancy of ROS levels between normal and diseased tissues, a variety of ROS-sensitive moieties or linkers have been developed to design ROS-responsive systems for the site-specific delivery of drugs and genes. In this review, we summarized the ROS-responsive chemical structures, mechanisms, and delivery systems, focusing on their current advances for precise drug/gene delivery. In particular, ROS-responsive nanocarriers, prodrugs, and supramolecular hydrogels are summarized in terms of their application for drug/gene delivery, and common strategies to elevate or diminish cellular ROS concentrations, as well as the recent development of ROS-related imaging probes were also discussed.

Cancer-Selective Bioreductive Chemotherapy Mediated by Dual Hypoxia-Responsive Nanomedicine upon Photodynamic Therapy-Induced Hypoxia Aggravation.

Stimuli-responsive drug delivery has rendered promising utilities in cancer treatment. Nevertheless, cancer selectivity as well as sensitivity still remains critical challenges that would undermine the therapeutic efficacy of chemodrugs and cause undesired systemic toxicity. Herein, a dual hypoxia-responsive drug delivery system was developed to enable photodynamic therapy (PDT)-induced drug release and drug activation intermediated via PDT-induced hypoxia. Particularly, tumor-targeting and hypoxia-dissociable nanoparticles (NPs) were self-assembled from the amphiphilic polyethylenimine-alkyl nitroimidazole [PEI-ANI, (PA)] and hyaluronic acid-chlorin e6 (HA-Ce6) to encapsulate bioreductive chemodrug, tirapazamine (TPZ). After systemic administration, the obtained PA/HA-Ce6@TPZ NPs enabled effective tumor accumulation due to HA-mediated cancer targeting. Upon receptor-mediated endocytosis, light irradiation (660 nm, 10 mW/cm2) produced high levels of reactive oxygen species to mediate PDT and generated a severe local hypoxic environment to dissociate the NPs and selectively release TPZ, as a consequence of hypoxia-triggered hydrophobic-to-hydrophilic transformation of ANI. In the meantime, TPZ was activated under hypoxia, finally contributing to a synergistic anticancer treatment between PDT and hypoxia-strengthened bioreductive chemotherapy. This study, therefore, demonstrates a suitable strategy for cancer-selective drug delivery as well as programmed combination therapy.

[Progress in Basic Research and Clinical Treatment of Multiple Pulmonary Nodules].

Lung cancer leads to the highest cancer-related morbidity and mortality worldwide. With the development of multi-slice spiral computed tomography technology and the implement of lung cancer screening, more and more lung nodules have been discovered, many of which are multiple pulmonary nodules. These pulmonary nodules are usually diagnosed as multiple primary lung adenocarcinomas from a pathological perspective. For multiple nodules with different imaging features, the preferred treatment methods are different, and the treatment of each lung nodule is still controversial. In recent years, the interactions between multiple lesions and the evolution of the lesions as well as the inter-tumoral and intratumoral homogeneity and heterogeneity of the genomics also arouse attention. Our review gathered the research progress in multiple pulmonary nodules from the points of histopathology, genomics and surgical management.
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Treatment of clinical T4 stage superior sulcus non-small cell lung cancer: a propensity-matched analysis of the surveillance, epidemiology, and end results database.

Purpose/Objective(s): Treatments for superior sulcus non-small cell lung cancer (SS-NSCLC) have evolved, but adequate treatments of T4 disease have not been found. The aim of our study was to evaluate the prognostic factors and optimal treatment strategy for patients with T4 SS-NSCLC. Materials/Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database (1973-2015) to identify patients diagnosed with T4 stage SS-NSCLC (according to the 7th edition American Joint Committee on Cancer (AJCC) staging system) from 2004 to 2015; those with M1 disease were excluded. Propensity score matching (PSM) with Kaplan-Meier and Cox proportional hazards' models was performed to estimate prognosis. Results: A total of 384 patients were included. The majority was male (59.4%) at stage IIIB (56.6%), with N2 accounting for 45.3%. A total of 47 patients underwent cancer-directed surgery, while radiotherapy alone was received by 60.2% of patients. Median overall survival (OS) and lung cancer-specific survival (LCSS) were 12 and 17 months, respectively, and the 5-year OS and LCSS rates were 15.8 and 25.4%, respectively. In the matched population, the median survival outcomes were better following surgery (OS: 25 compared with 9.0 months, P<0.001; LCSS: not available (NA) compared with 11.0 months, P<0.001). Multivariate Cox analysis showed that ages ≥ 66 years (hazard ratio (HR) = 1.639, P=0.001), unmarried status (HR = 1.356, P=0.034), and tumor size ≥ 6.0 cm (HR = 1.694, P<0.001) were associated with inferior OS. Cancer-directed surgery (HR = 0.537, P=0.009) and radiotherapy (HR = 0.644, P=0.006) were independent prognostic factors for patients with T4 SS-NSCLC. Conversely, in the subgroup analysis, favorable impacts of radiotherapy were observed for nonsurgical patients (OS: HR = 0.58, P<0.001; LCSS: HR = 0.55, P<0.001). Conclusion: Our study showed that T4 stage SS-NSCLC patients had a poor prognosis. Surgical resection remains the best option for those with resectable disease. For nonsurgical T4 SS-NSCLC patients, radiotherapy should be actively considered.

NFκB and TNFα as individual key molecules associated with the cisplatin-resistance and radioresistance of lung cancer.

Cisplatin-resistant (A549CisR and H292CisR) and radioresistant (A549R26 and H292R22) sub-line non-small cell lung cancer (NSCLC) cells were developed in our lab by long term treatment of parental cells with cisplatin or radiation. Our data showed no cross-resistance between these two sets of cell lines, indicating that molecular mechanisms of developing each resistance may be different. Using these sub-line cells, we sought to reveal the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, compared with parental cells. In qPCR analyses of screening DNA repair and cell survival-associated molecules, we identified NFκB and TNFα as the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, respectively, compared with parental cells. Western blot analysis of parental vs. resistant cells and the IHC staining of tumor tissues of A549P, A549CisR, and A549R26 cell-derived xenografts in mice confirmed such results. Next, studies using specific inhibitors of NFκB and TNFα and experiments using NFκB and TNFα-knocked down cells showed that inhibition or knockdown of NFκB overcame cisplatin-resistance, while inhibition or knockdown of TNFα increased radiosensitivity of radioresistant lung cancer cells. Therefore, these two molecules may be used as markers of the prognosis/diagnosis of individual resistance development during lung cancer treatment.