Roles of breast cancer resistance protein and organic anion transporting polypeptide 2B1 in gastrointestinal toxicity induced by SN-38 under inflammatory conditions.

Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.

Targeted Therapy for Cancers: From Ongoing Clinical Trials to FDA-Approved Drugs.

The development of targeted therapies has revolutionized cancer treatment, offering improved efficacy with reduced side effects compared with traditional chemotherapy. This review highlights the current landscape of targeted therapy in lung cancer, colorectal cancer, and prostate cancer, focusing on key molecular targets. Moreover, it aligns with US Food and Drug Administration (FDA)-approved drugs and drug candidates. In lung cancer, mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene rearrangements have emerged as significant targets. FDA-approved drugs like osimertinib and crizotinib specifically inhibit these aberrant pathways, providing remarkable benefits in patients with EGFR-mutated or ALK-positive lung cancer. Colorectal cancer treatment has been shaped by targeting the vascular endothelial growth factor (VEGF) and EGFR. Bevacizumab and cetuximab are prominent FDA-approved agents that hinder VEGF and EGFR signaling, significantly enhancing outcomes in metastatic colorectal cancer patients. In prostate cancer, androgen receptor (AR) targeting is pivotal. Drugs like enzalutamide, apalutamide, and darolutamide effectively inhibit AR signaling, demonstrating efficacy in castration-resistant prostate cancer. This review further highlights promising targets like mesenchymal-epithelial transition (MET), ROS1, BRAF, and poly(ADP-ribose) polymeras (PARP) in specific cancer subsets, along with ongoing clinical trials that continue to shape the future of targeted therapy.

Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials.

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.

The In Vitro and In Vivo Anticancer Effect of Photomed for Photodynamic Therapy: Comparison with Photofrin and Radachlorin.

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

Findings on In Vitro Transporter-Mediated Drug Interactions and Their Follow-Up Actions for Labeling: Analysis of Drugs Approved by US FDA between 2017 and 2021.

Understanding possible follow-up actions on in vitro findings helps determine the necessity of labeling for drug interactions. We analyzed information for in vitro findings on transporter-mediated interactions of drugs approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research for the last five years (i.e., 2017-2021) and their follow-up actions for labeling. Higher R values than the pre-defined cut-off were observed with 3.7-39.1% inhibitor drugs in a simple prediction. Among these drugs, 16-41.7% were labeled with their potential drug interactions, while results of supporting studies or scientific rationales were submitted for the other drugs leading to no interaction labeling. In vitro transporter substrates were reported with 1.7-67.6% of drugs. The interaction labels for these substrate drugs were observed in up to 40% of drugs, while the other drugs were not labeled on the drug interactions with claims for their low interaction potential, evidenced by clinical studies or scientific rationales. The systematic and comprehensive analysis in this study will provide insight into the management of in vitro findings for transporter substrate or inhibitor drugs.

Inflammatory Cytokine: An Attractive Target for Cancer Treatment.

The relationship between inflammation and cancer has attracted attention for a long time. The inflammatory tumor microenvironment consists of inflammatory cells, chemokines, cytokines, and signaling pathways. Among them, inflammatory cytokines play an especially pivotal role in cancer development, prognosis, and treatment. Interleukins, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-ß), interferons, and vascular endothelial growth factor (VEGF) are the representative inflammatory cytokines in various cancers, which may promote or inhibit cancer progression. The pro-inflammatory cytokines are associated with advanced cancer stages, resistance to immunotherapy, and poor prognoses, such as in objective response and disease control rates, and progression-free and overall survival. In this review, we selected colorectal, pancreatic, breast, gastric, lung, and prostate cancers, which are well-reported for an association between cancer and inflammatory cytokines. The related cytokines and their effects on each cancer's development and prognosis were summarized. In addition, the treatment strategies targeting inflammatory cytokines in each carcinoma were also described here. By understanding the biological roles of cancer-related inflammatory cytokines, we may modulate the inflammatory tumor microenvironment for potential cancer treatment.

Sensitive and valid assay for reliable evaluation of drug interactions mediated by human organic anion transporter 1 and 3 using 5-carboxyfluorescein.

Drug interactions can induce significant clinical impacts, either by increasing adverse effects or by decreasing the therapeutic effect of drugs, and thus, need to be explored thoroughly. Clinically significant drug interactions can be induced by organic anion transporter 1 (OAT1) and OAT3 when concomitant medications competitively interact with the transporters. The purposes of this study were to develop and validate a sensitive and selective analytical method for 5-carboxyfluorescein (5-CF) and optimize the experimental conditions for interaction studies. An analytical method using high-performance liquid chromatography (HPLC) equipped with a fluorescence detector was validated for accuracy, precision, matrix effect, recovery, stability, dilutional integrity, and carry-over effect. In addition, the 5-CF concentration, incubation period, and washing conditions for interaction study were optimized. Using a valid analytical method and optimized conditions, we performed an interaction study for OAT1 and OAT3 using 26 test articles. Some of the test articles showed strong inhibitory potency for the transporters, with IC50 values close to or less than 10 µM. The valid analysis method and optimized systems developed in this study can be utilized to improve the predictability of drug interactions in humans and consequently aid in successful disease treatment by maintaining appropriate systemic exposures.

Status of Medications Prescribed for Psychiatric Disorders in Korean Pediatric and Adolescent Patients.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (<20 years) who were diagnosed with schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, attention deficit-hyperactivity disorder (ADHD), or a tic disorder. Among these diseases, depressive episodes were the most common, followed by an anxiety disorder, ADHD, bipolar disorder, tic disorder, and schizophrenia. For each disease, prescriptions were categorized as full-label (approved indication with pediatric dosing in the package insert (PI)), partial-label (approved indication without pediatric dosing in the PI), and contraindication (contraindicated for the specific pediatric age in the PI). For schizophrenia, major depressive disorder, and anxiety disorder, more than 50% of the patients were prescribed partial-labeled medications. Additionally, more than 5% of patients with major depressive disorder were prescribed medications that were contraindicated for their age group. Our findings reveal that children with full-labeled psychiatric conditions are commonly administered drugs that are not explicitly approved for either their disease state or age, including off-label and unlicensed drugs. To use pharmaceuticals more safely, expanding drug indications using real-world data are needed.

Removal of chemical hazardous compounds using CATACOAT, a nano-platinum thermal catalyst system.

The performance of CATACOAT, a nano-platinum thermal catalyst system, was evaluated for the removal of chemical hazardous compounds from air. Xylene, benzene, styrene, and toluene were selected as standard volatile organic compounds (VOCs) in this study. In addition, formaldehyde was tested as a chemical hazardous compound. Each VOC, or formaldehyde, was evaporated in a 4,000 L chamber under controlled environments. At the maximum concentration point, CATACOAT was turned on and the concentrations of the chemical hazardous compounds were recorded for 5 h. The air purifier based on H-13-grade high-efficiency particulate air (HEPA) filter was tested in the same way to compare the effects of CATACOAT. Compared with the HEPA filter system, every VOC concentration was significantly decreased with the CATACOAT system only 0.025 h after turning on the air purifier (P values for xylene, benzene, styrene, and toluene are 0.00488, 0.01508, 0.00014, and 0.04690, respectively). After running the air cleaners for 5 h, every VOC and formaldehyde demonstrated significantly decreased concentrations with the CATACOAT system, compared with HEPA filter system (P values for xylene, benzene, styrene, toluene, and formaldehyde are 0.00034, 0.00009, 0.00008, 0.00001, and 0.00571, respectively). In conclusion, the CATACOAT may be a viable solution to control indoor air pollution.

Crosstalk between Autophagy and Inflammatory Processes in Cancer.

Inflammation is an adaptive response to tissue injury, which is a critical process in order to restore tissue functionality and homeostasis. The association between inflammation and cancer has been a topic of interest for many years, not only inflammatory cells themselves but also the chemokines and cytokines they produce, which affect cancer development. Autophagy is an intracellular self-degradative process providing elimination of damaged or dysfunctional organelles under stressful conditions such as nutrient deficiency, hypoxia, or chemotherapy. Interestingly, the signaling pathways that are involved in cancer-associated inflammation may regulate autophagy as well. These are (1) the toll-like receptor (TLR) signaling cascade, (2) the reactive oxygen species (ROS) signaling pathway, (3) the inflammatory cytokine signaling pathway, and (4) the IκB kinase (IKK)/Nuclear factor-κB (NF-κB) signaling axis. Moreover, the studies on the context-specific functions of autophagy during inflammatory responses in cancer will be discussed here. On that basis, we focus on autophagy inhibitors and activators regulating inflammatory process in cancer as useful candidates for enhancing anticancer effects. This review summarizes how the autophagic process regulates these key inflammatory processes and vice versa in various cancers.

Potential Therapeutic Approaches through Modulating the Autophagy Process for Skin Barrier Dysfunction.

Autophagy is an attractive process to researchers who are seeking novel potential treatments for various diseases. Autophagy plays a critical role in degrading damaged cellular organelles, supporting normal cell development, and maintaining cellular homeostasis. Because of the various effects of autophagy, recent human genome research has focused on evaluating the relationship between autophagy and a wide variety of diseases, such as autoimmune diseases, cancers, and inflammatory diseases. The skin is the largest organ in the body and provides the first line of defense against environmental hazards, including UV damage, chemical toxins, injuries, oxidative stress, and microorganisms. Autophagy takes part in endogenous defense mechanisms by controlling skin homeostasis. In this manner, regulating autophagy might contribute to the treatment of skin barrier dysfunctions. Various studies are ongoing to elucidate the association between autophagy and skin-related diseases in order to find potential therapeutic approaches. However, little evidence has been gathered about the relationship between autophagy and the skin. In this review, we highlight the previous findings of autophagy and skin barrier disorders and suggest potential therapeutic strategies. The recent research regarding autophagy in acne and skin aging is also discussed.

Prevalence of Anemia in Pediatric Patients According to Asthma Control: Propensity Score Analysis.

PURPOSE: To investigate whether the degree of asthma control is associated with anemia in pediatric patients. PATIENTS AND METHODS: A cross-sectional study was performed using a dataset from the Health Insurance Reviews & Assessment Service (HIRA) of South Korea in 2016, which included children and adolescent patients diagnosed with asthma. Binary logistic regression was used to assess the association between asthma control and the prevalence of anemia. RESULTS: A total of 236,429 patients under 18 years old were included in the study, including 233,975 patients with controlled and 2454 with uncontrolled asthma. Binary logistic regression after adjustment for confounding factors showed that patients with uncontrolled asthma had a 2.64-fold higher prevalence of anemia than those with well-controlled asthma (OR = 2.64, 95% CI: 2.16-3.22). While there was no effect of gender on the results, there was a statistically significant association between the prevalence of anemia and asthma control in patients under 13 years old. CONCLUSION: These findings suggest that the prevalence of anemia is inversely correlated with asthma control in pediatric patients. Further studies are necessary to obtain pathophysiological insight into the relationship between severe inflammatory diseases and anemia.

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders.

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy.

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of 50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

Enhanced production of reactive oxygen species in HeLa cells under concurrent low­dose carboplatin and Photofrin® photodynamic therapy.

Concurrent low­dose carboplatin/Photofrin® photodynamic therapy (ccPDT) has been shown to promote relapse­free complete tumor regression in cervical or endometrial cancer patients as a fertility­preservation therapy. This study aimed to investigate the molecular mechanism of the enhanced therapeutic efficacy of ccPDT by determining intracellular reactive oxygen species (ROS) and necrotic or apoptotic cell damage in HeLa cells loaded with fluorescent oxidant agents and Photofrin or/and carboplatin under light irradiation. The cytotoxic effects of ccPDT were compared when monitored with a light dose under carboplatin or Photofrin alone. Photofrin­PDT alone did not enhance either hydroxyl radicals (OH•) or superoxide anions (O2•-), but a slight enhancement of hydrogen peroxide (H2O2) production was observed. A larger enhancement of ROS production was obtained in a dose­dependent manner following ccPDT, especially OH• and H2O2, in conjunction with both necrotic and apoptotic cell death, compared with necrotic­prone PDT alone. The carboplatin­mediated Fenton reaction: 2[PtII]2 + H2O2 → [Pt2.25]4 + OH¯+ OH• was proposed to explain the dose­dependent enhancement of OH•. In conclusion, the therapeutic enhancement of ccPDT in vitro was attributable to the carboplatin­mediated synergetic production of OH▪ and apoptotic cellular damage, compared with Photofrin­PDT alone.

Optimal dose reduction algorithm using an attenuation-based tube current modulation method for cone-beam CT imaging.

To reduce the radiation dose given to patients, a tube current modulation (TCM) method has been widely used in diagnostic CT systems. However, the TCM method has not yet been applied to a kV-CBCT system on a LINAC machine. The purpose of this study is to investigate if a TCM method would be desirable in a kV-CBCT system for image-guided radiation therapy (IGRT) or not. We have developed an attenuation-based TCM method using prior knowledge from planning CT images of patients. The TCM method can provide optimized dose reductions without degrading image quality for kV-CBCT imaging. Here, we investigate whether or not our suggested TCM method is desirable to use in kV-CBCT systems to confirm and revise the exact position of a patient for IGRT. Patients go through diagnostic CT scans for RT planning; therefore, using information from prior CT images can enable estimations of the total X-ray attenuation through a patient's body in a CBCT setting for radiation treatment. Having this planning CT image allows to use the proposed TCM method in RT. The proposed TCM method provides a minimal amount of current for each projection, as well as total current, required to reconstruct the current modulated CBCT image with an image quality similar to that of CBCT. After applying a calculated TCM current for each projection, projection images were acquired and the current modulated CBCT image was reconstructed using a FDK algorithm. To validate the proposed approach, we used a numerical XCAT phantom and a real ATOM phantom and evaluated the performance of the proposed method via visual and quantitative image quality metrics. The organ dose due to imaging radiation was calculated in both cases and compared using the GATE simulation toolkit. As shown in the quantitative evaluation, normalized noise and SSIM values of the TCM were similar to those of conventional CBCT images. In addition, the proposed TCM method yielded comparable image quality to that of conventional CBCT images for both simulations and experimental studies as organ doses were decreased. We have successfully demonstrated the feasibility and dosimetric merit of a prototypical TCM method for kV-CBCT via simulations and experimental study. The results indicate that the proposed TCM method and overall framework can be a viable option for CBCT imaging that utilizes an optimal dose reduction without degrading image quality. Thus, this method reduces the probability for side effects due to radiation exposure.

Protective effects of GV1001 on myocardial ischemia­reperfusion injury.

The potential cardioprotective effects of the novel vaccine peptide GV1001 were evaluated in myocardial ischemia­reperfusion injury induced rat models. GV1001 is a human telomerase reverse transcriptase derived peptide, which has been reported to possess both anti­tumor and anti­inflammatory effects. The normal saline (control group) and various concentrations (0.001­10 mg/kg) of GV1001 were administered directly to the right ventricle anterior wall before induction of ischemia. The was induced by Tightening the snare around the left anterior descending coronary artery for 40 min, before releasing the snare for 10 min induced the myocardial ischemia­reperfusion injury and was conducted in Sprague­Dawley rats. The area at risk, histology, apoptotic cells, neutrophils and inflammatory cytokines were analyzed from the excised heart tissue following myocardial ischemia­reperfusion injury. The area at risk was protected by concentrations of GV1001 equal to or higher than 0.01 mg/kg. At 0.1 mg/kg and higher concentrations of GV1001, the hemorrhage in the heart was attenuated, while severe congestion was reported in the control group. Apoptotic cells, myeloperoxidase activity and inflammatory cytokines [tumor necrosis factor (TNF)­α and interleukin (IL)­6] revealed decreased levels in a dose­dependent manner with respect to GV1001 concentration. The group treated with 10 mg/kg GV1001 demonstrated 59.73% apoptotic cells (P<0.001), 48.14% neutrophil contents (P<0.001), 55.63% TNF­α (P<0.01) and 42.35% IL­6 (P<0.01) levels, compared with the control group. The novel vaccine peptide GV1001 provided protective effects on myocardial ischemia­reperfusion injury and, therefore, it should be considered as an alternative potential anti­inflammatory agent for myocardial ischemia­reperfusion injury.

Synchrotron tomographic images from human lung adenocarcinoma: Three-dimensional reconstruction and histologic correlations.

High-resolution tomographic images using synchrotron X-rays are expected to provide detailed reflection of microstructures, thereby allowing for the examination of histologic structures without destruction of the specimen. This study aims to evaluate the synchrotron tomographic images of mixed ground-glass opacity excised on 5-mm sections in comparison to pathologic examination. The Institutional Review Board of our institute approved this retrospective study, and written informed consent was obtained from each patient whose lung tissue would be used. Obtained lung cancer specimens were brought to the multiple Wiggler 6C beam line at the Pohang Light Source (PLS-II) in Korea, and phase contrast X-ray images were obtained in November 2016. The X-ray emanated from a bending magnet of the electron storage ring with electron energy of 3 GeV, and a typical beam current was 320 mA. Reconstructed tomographic images were compared with images from histologic slides obtained from the same samples. Pulmonary microstructures including terminal bronchioles, alveolar sacs, and vasculature were identified with phase contrast X-ray images. Images from normal lung tissue and mixed ground-glass opacity were clearly distinguishable. Hyperplasia of the interalveolar septum and dysplasia of microstructure were clearly identified. The imaging findings correlated well with hematoxylin-eosin stained specimens. Tomographic images using synchrotron radiation have the potential for clinical applications. With refinement, this technique may become a diagnostic tool for detection of lung cancer.

Association of MAGE A1-6 Expression with Lung Cancer Progression.

The melanoma-associated antigen (MAGE) genes are known to be expressed in various kinds of tumors including lung cancer. Although they are studied as targets for immunotherapy and tools for early detection of lung cancer, the correlation between MAGE expression and the prognosis in lung cancer has not been clarified. In this study, we evaluated the relationship between MAGE A1-6 gene expression and the clinical prognosis in lung cancer. Bone marrow aspirations were performed in 60 patients who were diagnosed as lung cancer and underwent lung cancer surgery between 2007 and 2008. Each bone marrow was examined using nested reverse transcription- polymerase chain reaction (RT-PCR) with the MAGE common primer to detect MAGE A1-6. Overall survival rate, disease-free survival rate, recurrence, and distant metastasis were reviewed retrospectively. Survival periods were analyzed using SPSS ver. 20.0. Of the total 60 lung cancer patients, 9 patients (15%) had MAGE A1-6. MAGE A1-6-positive patients showed poor overall survival and overall disease-free survival rates (43.8 ± 26.1, 43.2 ± 26.9 months, respectively) compared with MAGE A1-6-negative patients (54.4 ± 17.2, 44.8 ± 22.1 months, respectively). No significant difference was shown in either survival rates. In conclusion, MAGE A1-6 expression of bone marrow in lung cancer patients correlated with poor survival rates. We suggest that MAGE A1-6 may be considered as a novel prognostic factor for lung cancer which leads to effective follow-up and treatment.

Anticalcification effect of a combination of decellularization, organic solvents and amino acid detoxification on glutaraldehyde-fixed xenopericardial heart valves in a large-animal long-term circulatory model.

OBJECTIVES: We aimed to investigate the effect of a combination of anticalcification treatments, which were effective for preventing calcification in a small animal experiment, on glutaraldehyde-fixed xenopericardial valves using a large-animal long-term circulatory model. METHODS: Valved conduits were made of porcine pericardium as a leaflet and bovine pericardium as a conduit and were implanted into the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were divided into study (glutaraldehyde + combined anticalcification treatment, n = 6) and control (glutaraldehyde alone, n = 9) groups. Upon euthanization at 1 year, echocardiography and cardiac catheterization were performed. Explanted tissues were microscopically examined and analysed for measuring the calcium content. RESULTS: Haemodynamic data were obtained from 3 and 2 goats in the study and control groups, respectively. All valves, except 1, which was limited in motion, were functioning well on echocardiography; pressure gradients across the right ventricular outflow tract were lower in the study group on cardiac catheterization. On gross inspection, all leaflets remained mobile without calcific deposits in the study group, while most leaflets were heavily calcified in the control group. The calcium content in the leaflets remained low (≤4 µg/mg) in the study group. Among the leaflets explanted from goats that survived longer (>3 months), the calcium concentration was higher in the control group than in the study group [15.1 µg/mg (n = 5) vs 2.7 µg/mg (n = 5), respectively; P = 0.008). CONCLUSIONS: Porcine pericardial leaflets treated with our anticalcification protocol showed better function and less calcification than those treated with glutaraldehyde alone in the pulmonary position.