Chemically Recyclable Linear and Branched Polyethylenes Synthesized from Stoichiometrically Self-Balanced Telechelic Polyethylenes.

High-density polyethylene (HDPE) is a widely used commercial plastic due to its excellent mechanical properties, chemical resistance, and water vapor barrier properties. However, less than 10% of HDPE is mechanically recycled, and the chemical recycling of HDPE is challenging due to the inherent strength of the carbon-carbon backbone bonds. Here, we report chemically recyclable linear and branched HDPE with sparse backbone ester groups synthesized from the transesterification of telechelic polyethylene macromonomers. Stoichiometrically self-balanced telechelic polyethylenes underwent transesterification polymerization to produce the PE-ester samples with high number-average molar masses of up to 111 kg/mol. Moreover, the transesterification polymerization of the telechelic polyethylenes and the multifunctional diethyl 5-(hydroxymethyl)isophthalate generated branched PE-esters. Thermal and mechanical properties of the PE-esters were comparable to those of commercial HDPE and tunable through control of the ester content in the backbone. In addition, branched PE-esters showed higher levels of melt strain hardening compared with linear versions. The PE-ester was depolymerized into telechelic macromonomers through straightforward methanolysis, and the resulting macromonomers could be effectively repolymerized to generate a high molar mass recycled PE-ester sample. This is a new and promising method for synthesizing and recycling high-molar-mass linear and branched PE-esters, which are competitive with HDPE and have easily tailorable properties.

Tuning the crystallization and thermal properties of polyesters by introducing functional groups that induce intermolecular interactions.

The performance of sustainable polymers can be modified and enhanced by incorporating functional groups in the backbone of the polymer chain that increases intermolecular interactions, thus impacting the thermal properties of the material. However, in-depth studies on the role of intermolecular interactions on the crystallization of these polymers are still needed. This work aims to ascertain whether incorporating functional groups able to induce intermolecular interactions can be used as a suitable systematic strategy to modify the polymer thermal properties and crystallization kinetics. Thus, amide and additional ester groups have been incorporated into aliphatic polyesters (PEs). The impact of intermolecular interactions on the melting and crystallization behavior, crystallization kinetics, and crystalline structure has been determined. Functional groups that form strong intermolecular interactions increase both melting and crystallization temperatures but retard the crystallization kinetics. Selecting appropriate functional groups allows tuning the crystallinity degree, which can potentially improve the mechanical properties and degradability in semicrystalline materials. The results demonstrate that it is possible to tune the thermal transitions and the crystallization kinetics of PEs independently by varying their chemical structure.

The role of intermolecular interactions on melt memory and thermal fractionation of semicrystalline polymers.

The origin of melt memory effects associated with semicrystalline polymers and the physical parameters involved in this process have been widely studied in the literature. However, a comprehensive understanding of the role of intermolecular interactions on melt memory is still being developed. For this purpose, we have considered aliphatic polyesters and we have incorporated amide and additional ester groups. Inserting these additional functional groups, the strength of the intermolecular interactions increases widening the melt memory effect. Not only the presence of the functional groups but also the position of these groups in the repeating unit plays a role in the melt memory effect as it impacts the strength of the intermolecular interactions in the crystals. The study of the effect of intermolecular interactions has been extended to successive self-nucleation and annealing thermal fractionation experiments to explore for the first time the role of intermolecular forces on the fractionation capacity of linear polymers. We demonstrated that intermolecular interactions act as intrinsic defects interrupting the crystallizable chain length, thus facilitating thermal fractionation. Overall, this work sheds light on the role of intermolecular interactions on the crystallization behavior of a series of aliphatic polyesters.

Optimizing palliative chemotherapy for advanced invasive mucinous adenocarcinoma of the lung.

BACKGROUND: A primary pulmonary invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive adenocarcinoma of the lung. The prognosis of advanced IMA depending on chemotherapy regimen has not been fully investigated. Here, we compared the clinical outcomes of patients with advanced IMA treated with different palliative chemotherapies that included novel therapeutics. METHODS: This single-center retrospective study included a total of 79 patients diagnosed with IMA and treated with palliative chemotherapy. The primary outcome was the comparison of overall survival according to palliative chemotherapy type. Risk factors associated with death were evaluated as a secondary outcome. RESULTS: The study cohort of 79 patients comprised 27 progressive or recurrent cases and 52 initial metastatic patients. Thirteen patients (16.5%) received targeted therapy and 18 cases (22.8%) received immunotherapy. When we compared the survival outcomes of the different treatment regimens, patients with IMA treated by immunotherapy (undefined vs. non-immunotherapy 17.0 months, p < 0.001) had better overall survival rates. However, there was no difference in the prognosis between the cases treated with a targeted therapy (35.6 vs. non-targeted therapy 17.0 months, p = 0.211). None of the conventional regimens produced a better outcome. By multivariable analysis, immunotherapy (HR 0.28; 95% CI 0.11-0.74; P = 0.008) was found to be an independent prognostic factor for death. CONCLUSIONS: This study suggests that immunotherapy for patients with advanced IMA may provide favorable outcomes than other chemotherapy options.

Synthesis, Microstructure, and Properties of High-Molar-Mass Polyglycolide Copolymers with Isolated Methyl Defects.

An efficient, fast, and reliable method for the synthesis of high-molar-mass polyglycolide (PGA) in bulk using bismuth (III) subsalicylate through ring-opening transesterification polymerization is described. The difference between the crystallization (Tc ≈ 180 °C)/degradation (Td ≈ 245 °C) temperatures and the melting temperature (Tm ≈ 222 °C) significantly affects the ability to melt-process PGA homopolymer. To expand these windows, the effect of copolymer microstructure differences through incorporation of methyl groups in pairs using lactide or isolated using methyl glycolide (≤10% methyl) as comonomers on the thermal, mechanical, and barrier properties were studied. Structures of copolymers were characterized by nuclear magnetic resonance (1H and 13C NMR) spectroscopies. Films of copolymers were obtained, and the microstructural and physical properties were analyzed. PGA homopolymers exhibited an approximately 30 °C difference between Tm and Tc, which increased to 68 °C by incorporating up to 10% methyl groups in the chain while maintaining overall thermal stability. Oxygen and water vapor permeation values of solvent-cast nonoriented films of PGA homopolymers were found to be 4.6 cc·mil·m-2·d-1·atm-1 and 2.6 g·mil·m-2·d-1·atm-1, respectively. Different methyl distributions in the copolymer sequence, provided through either lactide or methyl glycolide, affected the resulting gas barrier properties. At 10% methyl insertion, using lactide as a comonomer significantly increased both O2 (32 cc·mil·m-2·d-1·atm-1) and water vapor (12 g·mil·m-2·d-1·atm-1) permeation. However, when methyl glycolide was utilized for methyl insertion at 10% Me content, excellent barrier properties for both O2 (2.9 cc·mil·m-2·d-1·atm-1) and water vapor (1.0 g·mil·m-2·d-1·atm-1) were achieved.

Convenient Colorimetric Detection of Cholesterol Using Multi-Enzyme Co-Incorporated Organic-Inorganic Hybrid Nanoflowers.

We have developed a microscale well-plate colorimetric assay for the multiplexed detection of cholesterol in clinical human blood samples. This system utilizes a novel multi-enzyme incorporated organic-inorganic hybrid nanoflower which entrap both cholesterol oxidase (ChOx) and horseradish peroxidase (HRP) as the organic components with copper phosphate as the inorganic component to detect cholesterol levels in blood samples. The hybrid nanoflowers, synthesized via an extremely simple but rapid sonication-mediated method within 5 min at room temperature, enable an efficient one-pot two-enzyme cascade reaction. The ChOx in the nanoflowers catalyze the generation of H2O2 only in the presence of cholesterol in the sample. This subsequently activates the HRP co-entrapped in the nanoflowers, thereby leading to the conversion of the employed chromogenic substrate, 3,3',5,5'-tetramethylbenzidine (TMB), into a blue-colored product. This strategy can be used to detect target cholesterol concentrations as low as 8 µM, with a linear range from 10 to 70 µM, which is suitable to diagnose high levels of cholesterol (hypercholesterolemia) with excellent stability over three weeks at room temperature. The biosensor also exhibited an excellent selectivity to detect target cholesterol even in the presence of common interfering biomolecules in human blood and showed a high degree of precision when employing human blood serum samples. Therefore, this hybrid nanoflower-based assay can be used in clinical practice for the multiplexed and reliable quantification of cholesterol, and readily extended to other enzymes to prepare multi-step cascade enzymatic reactions for various biotechnological applications.

Iridium-Catalyzed Direct C-H Amidation Polymerization: Step-Growth Polymerization by C-N Bond Formation via C-H Activation to Give Fluorescent Polysulfonamides.

We report a powerful strategy for activation of C-H bonds to produce polysulfonamides by an atom-economical and green method using iridium-catalyzed direct C-H amidation polymerization (DCAP). After screening various directing groups, additives, silver salts, concentrations, and temperatures to optimize DCAP, high-molecular-weight (up to 149 kDa) and defect-free polysulfonamides were synthesized from various bis-sulfonyl azides. Although these polymers do not have conventional fluorescent conjugated cores, they emit blue light with large Stokes shifts and high quantum yields upon photoexcitation owing to an excited-state intramolecular proton-transfer process.

Factors Affecting Life-Sustaining Treatment Decisions and Changes in Clinical Practice after Enforcement of the Life-Sustaining Treatment Decision (LST) Act: A Tertiary Hospital Experience in Korea.

Purpose: In Korea, the act on hospice and palliative care and decisions on life-sustaining treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement. Materials and Methods: This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020. Results: 5896 patients completed LST documents, of which 2704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after ICU admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (OR, 1.724; 95% CI, 1.538-1.933; p<0.001), unmarried status (OR, 1.309; 95% CI, 1.097-1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340-1.765; p<0.001), malignancy (OR, 1.864; 95% CI, 1.628-2.133; p<0.001), and changes in timing on the first year versus following year (OR, 1.124, 95% CI, 1.003-1.260, p=0.045) were related to a higher self-documentation rate. Conclusion: Age < 65, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.

Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

Oxidative stress is associated with C-reactive protein in nondiabetic postmenopausal women, independent of obesity and insulin resistance.

OBJECTIVE: Oxidative stress is associated with obesity, metabolic syndrome and inflammation, suggesting it could be an early event in the pathology of chronic diseases. We tested the hypothesis that elevated levels of oxidative stress markers are associated with increased C-reactive protein (CRP) and that this is independent of obesity and insulin resistance. RESEARCH DESIGN AND METHODS: This study was cross-sectional designed and nondiabetic postmenopausal women (n = 1821) with CRP levels ≤10 mg/l was enrolled. The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4). The degree of insulin resistance was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR). We measured oxidative stress using urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and plasma oxidized low-density lipoprotein (ox-LDL). RESULTS: After adjustments for age and lifestyle habits, including smoking and drinking, we found higher body mass index (BMI) and HOMA-IR scores in Q2 and Q3 vs Q1. The Q4 BMI and HOMA-IR scores were higher than all other quartiles. The plasma ox-LDL was higher in Q4 than in Q1. Urinary 8-epi-PGF2α was higher in Q3 and Q4 than in Q1 or Q2. Urinary 8-epi-PGF2α positively correlated with CRP (r = 0·235, P < 0·001), whereas no correlation was found between ox-LDL and CRP. Multiple linear regression analyses of BMI and HOMA-IR showed that the association between urinary 8-epi-PGF2α and CRP levels remained significant (P < 0·001). CONCLUSIONS: Oxidative stress measured by increased concentration of urine 8-epi-PGF2α is strongly associated with CRP levels. This finding was independent of obesity and insulin resistance in nondiabetic postmenopausal women.

Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness and endothelial cell tube formation.

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling during normal physiological situations and pathological implications such as tumor invasion and metastasis. MMP inhibitors were screened from extracts of medicinal herbs by an enzymatic assay using the MMP-14 catalytic domain. Among samples tested, a methanol extract of the root of Dalbergia odorifera T. CHEN (Leguminosae) showed the strongest inhibitory activity. The inhibitory component was purified through fractionation methods and identified as fisetin, abundant in many fruits and vegetables. In addition to inhibition of MMP-14, fisetin inhibits MMP-1, MMP-3, MMP-7, and MMP-9, more efficiently than a naturally occurring MMP inhibitor tetracycline. Fisetin dose-dependently inhibits proliferation of fibrosarcoma HT-1080 cells and human umbilical vascular endothelial cells (HUVECs), MMP-14-mediated activation of proMMP-2 in HT-1080 cells, invasiveness of HT-1080 cells, and in vitro tube formation of HUVECs. Therefore, fisetin could be valuable as a chemopreventive agent against cancer and a lead compound for development of therapeutic MMP inhibitors.

Optimal Definition of Oligometastasis Showing Survival Benefits of Local Therapies during Tyrosine Kinase Inhibitor Treatment.

PURPOSE: We aimed to investigate the feasibility of four criteria on oligometastasis (OM) concerning clear survival benefits of local therapy (LT) during tyrosine kinase inhibitor (TKI) treatment in non-small cell lung cancer (NSCLC). Materials and Methods: This single-center, retrospective study included patients with advanced NSCLC who received LT because of OM during TKI treatment at Asan Medical Center from January 2011 to December 2020. At the application of LT OM was classified according to four criteria: TNM, European Organization for Research and Treatment of Cancer Lung Cancer Group (EORTC-LCG), National Comprehensive Network (NCCN), and ORGAN. We compared survival outcomes between patients with and without OM. RESULTS: The median overall survival of the 117 patients included in the analysis was 70.8 months (95% confidence interval [CI], 56.6 to 85.1). The patients with OM meeting all four criteria (hazard ratio [HR] with 95% CI of TNM criteria 0.24 with 0.10-0.57; p=0.001, EORTC-LCG criteria 0.34 with 0.17-0.67; p=0.002, NCCN criteria 0.41 with 0.20-0.86; p=0.018 and ORGAN criteria 0.33 with 0.18-0.60; p < 0.001) had significantly longer survival compared with patients who did not after adjusting for confounding factors. Furthermore, increasing the number of extra-thoracic metastatic organs to two or more were independent predictive factors for worse survival outcomes (2 organs: HR, 3.51; 95% CI, 1.01 to 12.14; p=0.048; 3 organs: HR, 4.31; 95% CI, 0.94 to 19.73; p=0.060; 4 organs: HR, 24.47; 95% CI, 5.08 to 117.80; p < 0.001). CONCLUSION: Patients with OM defined by all four criteria showed prognostic benefits from LT during TKI therapy.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

Clinical outcomes of immune checkpoint inhibitors in unresectable or metastatic combined hepatocellular-cholangiocarcinoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC-CCA (cHCC-CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC-CCA. METHODS: Among 101 patients with histologically documented cHCC-CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated. RESULTS: The median age was 64 years (range 38-83) and 84% (n = 21) of patients were males. Most patients had Child-Pugh A liver function (n = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab (n = 17, 68%) was the most frequently used ICI, followed by pembrolizumab (n = 5, 20%), atezolizumab plus bevacizumab (n = 2, 8%), and ipilimumab plus nivolumab (n = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1-5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9-35.2 months), the median PFS was 3.5 months (95% CI 2.4-4.8 months), and the median OS was 8.3 months (95% CI 6.8-9.8 months). The ORR was 20.0% (n = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2-12.0 months). CONCLUSIONS: ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC-CCA.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

CT Findings From Interstitial Lung Diseases in Patients With Metastatic Breast Cancer Treated With Fam-Trastuzumab Deruxtecan: A Single Institutional Experience.

This single-institute, retrospective cohort study enrolled patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with trastuzumab deruxtecan between August 2017 and January 2021 from four previous studies. Of 31 patients, 4 (12.9%) had interstitial lung disease (ILD). The dominant pattern observed on computed tomography was organizing pneumonia (100%), comprising subpleural consolidations in the lung periphery. However, no dominant distribution was observed in radiological lesions of the lungs. Of all the tested patients, lower lobe predominance was noted in 2 (50.0%) patients, upper lobe predominance in 1 (25.0%) patient, and diffused lobe distribution in 1 (25.0%) patient. All events were confined to the Common Terminology Criteria for Adverse Events grade 1 or 2 (100%). None of the patients died. Despite the small number of cases investigated, the incidence of trastuzumab deruxtecan-induced ILD in the Korean population was comparable to that previously reported.

Bioconjugation of L-3,4-dihydroxyphenylalanine containing protein with a polysaccharide.

We describe the simple bioconjugation strategy in combination of periodate chemistry and unnatural amino acid incorporation. The residue specific incorporation of 3,4-dihydroxy-l-phenylalanine can alter the properties of protein to conjugate into the polymers. The homogeneously modified protein will yield quinone residues that are covalently conjugated to nucleophilic groups of the amino polysaccharide. This novel approach holds great promise for widespread use to prepare protein conjugates and synthetic biology applications.

Evaluation of nanoparticle drug-delivery systems used in preclinical studies.

Multifunctional nanoparticles have been identified as a promising drug-delivery system for sustainable drug release. The structural and size tunability and disease-targeting ability of nanoparticles have made them more suitable for multiple drug loading and delivery, thereby enhancing therapeutic results through synergistic effects. Nanoparticulate carriers with specific features such as target specificity and stimuli-responsiveness enable selective drug delivery with lower potential side effects. In this review we have classified the recently published articles on polymeric and inorganic nanoparticle-mediated drug delivery into three different categories based on functionality and discussed their efficiency for drug delivery and their therapeutic outcomes in preclinical models. Most of the drug-loaded nanodelivery systems discussed have demonstrated negligible or very low systemic toxicity throughout the experimental period in animal models compared with free drug administration. In addition, some challenges associated with the translation of nanoparticle-based drug carrier responses to clinical application are highlighted.

Effect of periphery cationic substituents of porphyrin on the B-Z transition of poly[d(A-T)2], poly[d(G-C)2] and their binding modes.

The binding mode of cationic porphyrin (trans-BMPyP) with poly[d(G-C)2] and poly[d(A-T)2] was examined according to the site of the periphery cationic methyl pyridine ion of the cationic porphyrin (o-, m-, p-) as well as the possibility of a B-Z transition depending on the binding modes by measuring the absorption spectrum and circular dichroism (CD). The negative band found in the soret region showed the intercalation mode of m- and p-trans-BMPyP-poly[d(G-C)2] to the DNA base pairs, but no B-Z transition was induced. On the other hand, the distinctive bisignate band found in the soret region of the CD spectrum for m- and p-trans-BMPyP-poly[d(A-T)2] suggests that m- and p-trans-BMPyP have an effective extensive stacking-based binding mode along with the skeleton of poly[d(A-T)2], wherein the B-Z transition was induced through extensive stacking. The difference in binding mode was attributed to the difference in the molecular structure depending on the site of the periphery cationic methyl pyridine ion in the cationic porphyrin. In other words, o-trans-BMPyP is nonplanar because of the steric hindrance of the cationic methyl pyridine ion at the o-site. In contrast, m- and p-trans-BMPyP are planar, but not all porphyrins with a planar structure undergo the B-Z transition. In conclusion, a B-Z transition is induced if the structure of a porphyrin is planar and the binding mode allows the porphyrins to be stacked effectively along the DNA skeleton, not in a binding mode where the porphyrin is intercalated to the DNA.Communicated by Ramaswamy H. Sarma.

Association of EGFR mutations in second primary lung cancer and HER2 expression in breast cancer survivors.

BACKGROUND: The incidence of second primary lung cancer (SPLC) is increasing with longer survival rates from breast cancer. Despite of studies to suggest the mutual exclusivity of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2) in several cancers, the effect of HER2 expression in breast cancer on EGFR mutations in SPLC is unclear. Therefore, this study aimed to determine the association between HER2 expression and EGFR mutations. METHODS: We conducted a retrospective cohort study of breast cancer survivors diagnosed with SPLC after breast cancer treatment between 1997 and 2018. We investigated the association between HER2 expression in breast cancer and EGFR mutations in SPLC, specifically focusing on negative correlations by using logistic regression analysis. RESULTS: EGFR mutations in SPLC were detected in 19 of 38 patients. Analysis for HER2 revealed a statistically significant difference in the proportion of EGFR mutations between patients with SPLC and previous HER2 positive breast cancer (43.5%) and those with SPLC and previous HER2 negative breast cancer (90.0%; P=0.021). The ratio of EGFR mutations decreased with the degree of HER2 expression in patients with previous breast cancer (90.0%: for no HER2 expression, 62.5% for HER2 1+, 0.0% for HER2 2+, and 41.7% for HER2 3+; P=0.018). Multivariate logistic analyses revealed that EGFR mutations in SPLC were significantly associated with age [odds ratio (OR): 1.11, 95% confidence interval (CI): 1.01-0.23, P=0.039] and HER2 positive status (OR: 0.04, 95% CI: 0.01-0.56, P=0.017). CONCLUSIONS: This study suggests that the frequency of EGFR mutations in SPLC may be associated with low HER2 expression in previous breast cancer.