Multiple enteric muco-submucosal elongated polyps causing intussusception.

A 20-year-old woman presented to our hospital with abdominal pain. Abdominal computed tomography revealed multiple masses in the upper jejunum, which were suspected as lipomas. Partial resection of the small intestine, including the masses, was performed on the same day due to intussusception secondary to the masses. Pathological examination revealed that the masses consisted of mucosa and edematous submucosa with multiple dilated blood vessels and lymphatic ducts without muscularis propria. The masses were diagnosed as multiple muco-submucosal elongated polyps (MSEP), a type of non-neoplastic polyp. MSEP was originally named colonic MSEP, but with the development of endoscopic techniques and imaging tests, similar polyps have been reported to occur not only in the colon but also in the entire intestinal tract. In this case, multiple MSEPs in the upper jejunum caused intussusception. As reported cases of multiple lesions causing intussusception are few, our case may help to clarify the pathogenesis of this disease.

Wedge Resection for Duodenal Gastrointestinal Stromal Tumors: Surgical Management and the Clinicopathological Outcome.

We analyzed the clinicopathological characteristics of six patients with duodenal gastrointestinal stromal tumor (dGIST) resected in our hospital between 2005 and 2020. The patients (5 males, 1 female) were aged from 43 to 83 years old (mean: 63.7 years old). With respect to the preoperative diagnosis, one patient was diagnosed with dGIST by a biopsy, and five patients were diagnosed with suspected dGIST by esophagogastroduodenoscopy (EGD). The tumor locations were the third portion in four cases, second portion in one, and fourth portion in one. The pathological stages were I in four patients, II in one, and IIIB in one. All patients were discharged 12.8 days (10-15 days) postoperatively without complications, such as pancreatic fistula or suture deficiency. Regarding the prognosis, all patients are alive without recurrence. The wedge resection is a reasonable option for resection of dGIST and should be routinely considered if technically feasible.

Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor.

Targeted therapies for malignant melanoma have improved patients' prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma.

Male Infants Born to Older Pregnant Women Are Affected by Maternal Physique at the Beginning of the Pregnancy through Birth until 18 Months of Age.

We have previously reported a positive correlation between the body mass index (BMI) of mothers and the Kaup index of infants at birth and that this correlation may have a stronger influence on the male infants, born to older mothers. Therefore, in this study, we aimed to clarify the correlation between maternal age and gender of the infants as maternal BMI and the Kaup index of infants from birth till 18 mo of age. This study was conducted from April 2010 to September 2011 in Japan. Public health nurses and registered dietitians interviewed the mothers individually under anonymous conditions, and they transferred the required information from the maternity passbook at the 18-mo health checkup. In male infants, significant positive correlations were demonstrated between maternal BMI at the beginning of pregnancy and the Kaup index of infants in mothers older than 35 y when the infants were at birth, at 4 mo and at 18 mo old. In female infants, there was no correlation between maternal BMI and the Kaup index of infants at birth. However, significant positive correlations were demonstrated between maternal BMI and the Kaup index of infants in mothers in their 20s and older than 35 y old when the infants were 4 and 18 mo old. Women who plan on pregnancy and medical professionals need to know that the maternal physique at the beginning of pregnancy affects the physique of the infants at birth and at 4 mo and 18 mo old by gender of the infants.

The number of CD34+CD133+ hematopoietic stem cells residing in umbilical cord blood (UCB) units is not correlated with the numbers of total nucleated cells and CD34+ cells: a possible new indicator for quality evaluation of UCB units.

Umbilical cord blood transplantation (UCBT) is often associated with delayed neutrophil and platelet recovery. Engraftment failure is another major obstacle. Several factors influence these serious complications, including the numbers of total nucleated cells (TNCs) and CD34+ cells which have been used as reliable factors for selecting UCB units for transplantation. However, whether both factors are reliable indices of the hematopoietic stem cell (HSC) activity of UCB units remains unknown. To evaluate the quality of UCB units, we quantified the actual number of transplantable CD34+CD133+ HSCs (tHSCs) residing in UCB units. The number of tHSCs was not correlated with the numbers of TNCs or CD34+ cells. These results strongly suggest that neither factor reflects the numbers of tHSCs residing in UCB units. To validate the significance of the number of tHSCs, further analysis is required to determine whether the number of tHSCs residing in UCB units is useful as a new indicator for the quality assessment of UCB units.

A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells.

We previously identified CD34-negative (CD34-) severe combined immunodeficiency (SCID)-repopulating cells as primitive hematopoietic stem cells (HSCs) in human cord blood. In this study, we develop a prospective ultra-high-resolution purification method by applying two positive markers, CD133 and GPI-80. Using this method, we succeed in purifying single long-term repopulating CD34- HSCs with self-renewing capability residing at the apex of the human HSC hierarchy from cord blood, as evidenced by a single-cell-initiated serial transplantation analysis. The gene expression profiles of individual CD34+ and CD34- HSCs and a global gene expression analysis demonstrate the unique molecular signature of CD34- HSCs. We find that the purified CD34- HSCs show a potent megakaryocyte/erythrocyte differentiation potential in vitro and in vivo. Megakaryocyte/erythrocyte progenitors may thus be generated directly via a bypass route from the CD34- HSCs. Based on these data, we propose a revised road map for the commitment of human CD34- HSCs in cord blood.

TGF-ß Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

It is generally thought that the proliferative capacity and differentiation potential of somatic stem cells, including mesenchymal stromal/stem cells (MSCs) and hematopoietic stem cells, decline with age. We investigated the effects of aging on human bone-derived MSCs expressing CD271 and SSEA-4 (double-positive MSCs [DPMSCs]). The percentages of DPMSCs in bone tissue decreased significantly with age. The DPMSCs from elderly patients (old DPMSCs) showed cellular senescence, which was evidenced by low growth potential, high senescence-associated ß-galactosidase activity, and elevated p16 and p21 CDK inhibitor levels. Moreover, old DPMSCs showed weak osteogenic differentiation potential and less hematopoiesis-supporting activity in comparison with young DPMSCs. Interestingly, the addition of transforming growth factor ß2 (TGF-ß2) induced cellular senescence in young DPMSCs. With the exception of the adipogenic differentiation potential, all of the aging phenomena observed in old DPMSCs were reversed by the addition of anti-TGF-ß antibodies. These results suggest that, in part, old DPMSCs accelerate cellular senescence through TGF-ß signaling.

Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.

Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2) drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. First, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs. In the drug sensitivity analysis, both afatinib and neratinib produced an antitumor effect in most of the HER2-amplified cell lines. However, some cells were not sensitive to the drugs. When the molecular profiles of the cells were compared based on the drug sensitivities, we found that cancer cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable synergistic effect. Among 123 clinical samples, we found 19 cases of HER2 amplification and three cases of oncogenic mutations. In conclusion, afatinib and neratinib are promising therapeutic options for the treatment of HER2-amplified gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug insensitiveness in HER2-amplified gastric cancer.

Arterial stiffness in junior high school students: Longitudinal observations.

BACKGROUND: Early atherosclerotic change is found even in childhood, and there is an urgent need to clarify the factors causing childhood atherosclerosis and take preventive measures. Early detection of the contributing risk factors is crucial to facilitate preventive measures. Pulse wave velocity (PWV) is a widely used technique for the assessment of atherosclerosis in children. METHODS: Lifestyle questionnaire, brachio-ankle PWV (baPWV) and anthropometric data were obtained from junior high school students in an urban area of Japan between 2006 and 2008, from seventh to ninth grades. RESULTS: Mean baPWV increased from 867.4 ± 99.5 m/s to 944.5 ± 117.5 m/s in boys, and from 864.0 ± 99.5 m/s to 923.0 ± 101.3 m/s in girls. Obese students had higher baPWV than non-obese students in both genders across each grade. On logistic regression analysis of ninth grade student data, high baPWV was dependent on systolic blood pressure (SBP), time watching television (TV) and symptoms of depression and anxiety, whereas low baPWV was dependent on time playing video games, light exercise, sleep and indoor play, as well as good friendship and motivation. CONCLUSION: Systolic blood pressure, time watching TV, and symptoms of depression and anxiety may contribute to arterial stiffness and be related to obesity in junior high school students.

Estimation of age-related DNA degradation from formalin-fixed and paraffin-embedded tissue according to the extraction methods.

Techniques for the extraction and use of nucleic acids from formalin-fixed and paraffin-embedded (FFPE) tissues, preserved over long time periods in libraries, have been developed. However, DNA extracted from FFPE tissues is generally damaged, and long-term storage may affect DNA quality. Therefore, it is important to elucidate the effect of long-term storage on FFPE tissues and evaluate the techniques used to extract DNA from them. In the present study, the yield, purity, and integrity of DNA in FFPE tissue samples was evaluated. Two DNA extraction techniques were used: A silica-binding DNA collection method using QIAamp DNA FFPE Tissue kit (QIA) and a total tissue DNA collection method using a WaxFree DNA extraction kit (WAX). A total of 25 FFPE tissues from lung adenocarcinomas were studied, which had been surgically resected and fixed at Okayama University Hospital prior to examination and subsequent storage at room temperature for 0.5, 3, 6, 9 and 12 years. Extracted DNA was quantified using ultraviolet absorbance, fluorescent dye, and quantitative polymerase chain reaction (qPCR). The quality of the DNA was defined by the absorbance ratio of 260 to 280 nm (A260/280) and Q-score, which is the quantitative value of qPCR product size ratio. The results demonstrated that the yield of total DNA extracted using WAX was significantly greater than when QIA was used (P<0.01); however, DNA extracted using WAX included more contaminants and was significantly more fragmented compared with DNA extracted using QIA (P<0.01). Aging had no significant effect on absolute DNA yield or DNA purity, although it did significantly contribute to increased DNA degradation for both QIA and WAX extraction (QIA P=0.02, WAX P=0.03; 0.5 years vs. 3 years, QIA P<0.01, WAX P=0.03; 9 years vs. 12 years). Both extraction methods are viable depending on whether high yield or high quality of extracted DNA is required. However, due to the increased degradation with age, storage time limits the available DNA in FFPE tissues regardless of the extraction method.

Elacridar, a third-generation ABCB1 inhibitor, overcomes resistance to docetaxel in non-small cell lung cancer.

Docetaxel is a third-generation chemotherapeutic drug that is widely used in the treatment of patients with non-small cell lung cancer (NSCLC). However, the majority of patients with NSCLC eventually acquire resistance to the treatment. In the present study, the mechanism of acquired resistance to docetaxel treatment in lung cancer cells was investigated. The three NSCLC cell lines, H1299 with wild-type epidermal growth factor receptor (EGFR), EGFR-mutant HCC4006 and HCC827, and experimentally established docetaxel-resistant (DR) cells, H1299-DR, HCC827-DR, and HCC4006-DR were used with stepwise increases in concentrations of docetaxel. It was demonstrated that the established cell lines showed resistance to docetaxel and EGFR-tyrosine kinase inhibitors (TKIs). Molecular analysis revealed that all of the resistant cell lines highly expressed ATP binding cassette subfamily B member 1 (ABCB1), which is also known as P-glycoprotein or MDR1. Furthermore, HCC827-DR and HCC4006-DR cells exhibited a cancer stem cell-like marker and epithelial-to-mesenchymal transition features, respectively. Elacridar (GF120918), a third-generation inhibitor of ABCB1, was able to overcome resistance to docetaxel. Additionally, knockdown of ABCB1 using small interfering RNA (si)-ABCB1 recovered sensitivity to docetaxel. However, elacridar and si-ABCB1 could not recover sensitivity to EGFR-TKIs in established resistant cells. The results of the present study revealed that docetaxel-resistant NSCLC cells also acquired cross-resistance to EGFR-TKI therapy through mechanisms other than ABCB1, that ABCB1 serves an important role in acquired resistance to docetaxel in lung cancer, and that combination therapy with elacridar can overcome ABCB1-mediated docetaxel resistance.

Yes1 signaling mediates the resistance to Trastuzumab/Lap atinib in breast cancer.

BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in approximately 15-23% of breast cancers and these cancers are classified as HER2-positive breast cancer. Trastuzumab is the first-line targeted therapeutic drug for HER2-positive breast cancer and has improved patient overall survival. However, acquired resistance to trastuzumab is still a critical issue in breast cancer treatment. We previously established a trastuzumab-resistant breast cancer cell line (named as BT-474-R) from a trastuzumab-sensitive HER2-amplified cell line BT-474. Lapatinib is also a molecular-targeted drug for HER2-positive breast cancer, which acquired the resistance to trastuzumab. Acquired resistance to lapatinib is also an issue to be conquered. METHODS: We established trastuzumab/lapatinib-dual resistant cell line (named as BT-474-RL2) by additionally treating BT-474-R with lapatinib. We analyzed the mechanisms of resistance to trastuzumab and lapatinib. Besides, we analyzed the effect of the detected resistance mechanism in HER2-positive breast cancer patients. RESULTS: Proto-oncogene tyrosine-protein kinase Yes1, which is one of the Src family members, was amplified, overexpressed and activated in BT-474-R and BT-474-RL2. Silencing of Yes1 by siRNA induced both BT-474-R and BT-474-RL2 to restore the sensitivity to trastuzumab and lapatinib. Pharmaceutical inhibition of Yes1 by the Src inhibitor dasatinib was also effective to restore the sensitivity to trastuzumab and lapatinib in the two resistant cell lines. Combination treatment with dasatinib and trastuzumab induced down-regulation of signaling molecules such as HER2 and Akt. Moreover, the combination treatments induced G1-phase cell-cycle arrest and apoptosis. Consistent with cell line data, high expression of Yes1 mRNA was correlated with worse prognosis in patients with HER2-positive breast cancer. CONCLUSION: Yes1 plays an important role in acquired resistance to trastuzumab and lapatinib in HER2-positive breast cancer. Our data suggest that pharmacological inhibition of Yes1 may be an effective strategy to overcome resistance to trastuzumab and lapatinib.

High Maternal Age and Low Pre-Pregnancy Body Mass Index Correlate with Lower Birth Weight of Male Infants.

In Japan, the percentage of leanness has been increasing in young women, and the percentage of low birth weight infants (< 2,500 g) has increased. Moreover, the average age of primiparas rose 3.5 years during the last 30 years. The purpose of this study was to clarify the relationship between maternal age and the influence of maternal pre-pregnancy physique on the neonatal physique of infants. Questionnaires were issued to the participants and collected when they submitted their gestational notifications at their local ward office in Kyoto Prefecture. After delivery, we obtained information on the course of the pregnancy and the neonatal physique of the infants from the participant's maternal passbooks. A total of 454 mothers (age 20 ≥) were analyzed: 161 young mothers (aged 20 to 29 years), 185 mothers (aged 30 to 34 years), and 108 older mothers (age ≥ 35). Overall, the mean rate of leanness (pre-pregnancy BMI < 18.5) was 23.8%. We found that birth weight was significantly lower in female infants, born to lean young mothers, compared to non-lean young mothers, whereas no significant difference was detected in other mothers (age ≥ 30), irrespective of pre-pregnancy BMI. By contrast, male infants, born to older lean mothers (age ≥ 35), showed significantly lower birth weight. Thus, maternal pre-pregnancy BMI exerts differential effects on the fetal growth (neonatal physique), depending on the maternal age and the sex of infants. We need to improve BMI in pre-pregnancy women, especially those in the twenties and 35 years old or over.

Targeting the miR-200c/LIN28B axis in acquired EGFR-TKI resistance non-small cell lung cancer cells harboring EMT features.

MicroRNA (miR)-200 family members (miR-200s) are frequently silenced in advanced cancer and have been implicated in the process of epithelial-to-mesenchymal transition (EMT). We previously reported that miR-200s were silenced through promoter methylation in acquired EGFR-tyrosine kinase inhibitor (TKI) resistant non-small cell lung cancer (NSCLC) cells harboring EMT features. In this study, we examined the functional role of miR-200s in NSCLC cells and investigated a novel approach to overcoming acquired EGFR-TKI resistance. In the analysis of NSCLC cell lines, each of the miR-200s expression-silenced cell lines showed promoter methylation. Significant correlations between miR-200c silencing and several oncogenic pathway alterations, including EMT-changes and LIN28B overexpression, were observed in the database analysis. In addition, EGFR-wild type cell lines had lower miR-200s expression levels than EGFR-mutant cell lines. The introduction of miR-200c using pre-miR-200c caused LIN28B suppression in cells with acquired EGFR-TKI resistance that harbored EMT features. Interestingly, both the introduction of miR-200c and the knockdown of LIN28B produced an antitumor effect in acquired EGFR-TKI resistance cells, whereas these manipulations were not effective in parental cells. The miR-200c/LIN28B axis plays an important role in cells with acquired resistance to EGFR-TKI that harbor EMT features and might be a useful therapeutic target for overcoming resistance.

Effects of implementing an "enhanced recovery after surgery" program on patients undergoing resection of hepatocellular carcinoma.

PURPOSE: To evaluate the effects of implementing an "enhanced recovery after surgery" (ERAS) program on the feasibility, safety, and effectiveness of extensive and potentially curative liver resection for hepatocellular carcinoma (HCC). METHODS: We compared clinicopathologic factors, surgical factors, and outcomes of patients who underwent extended hepatectomy (defined as resection of more than two sections) for HCC, before and after the introduction of an ERAS program. RESULTS: Operating times and postoperative hospital stay were significantly shorter, and total volume infused during surgery was significantly lower, for the ERAS group than for the control group. Although the ERAS group had a significantly lower percentage of patients with retention of abdominal drainage, this group had a higher frequency of abdominal paracentesis in patients without intraoperative abdominal drainage. Oral dietary intake and the ability to walk steadily resumed significantly earlier in the ERAS group. Postoperative serum concentrations of albumin and cholinesterase were significantly higher in the ERAS group than in the control group. CONCLUSIONS: The ERAS program was feasible and effective for patients with chronic liver disease undergoing extended liver resection for HCC, because it allowed earlier oral dietary intake and promoted faster postoperative recovery.

Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies.

BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. MATERIALS AND METHODS: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. RESULTS: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. CONCLUSION: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

BACKGROUND/AIM: Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. PATIENTS AND METHODS: There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. RESULTS: With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. CONCLUSION: Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone.

The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells.

Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1ß, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.

Establishment and molecular characterization of cell lines from Japanese patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive disease that is resistant to conventional therapies. Cell lines are useful models for studying the biological characteristics of tumors; therefore, the establishment of MPM cell lines is valuable for exploring novel therapeutic strategies for MPM. In the present study, 4 MPM cell lines (YUMC8, YUMC44, YUMC63, and YUMC64) were established, which consisted of 2 epithelioid and 2 sarcomatoid mesothelioma histological subtypes, from Japanese patients with MPM. The DNA methylation status, mutations, copy number gains, protein expression of representative genes, and the sensitivity to several drugs were examined in these 4 cell lines. Methylation of P16 was demonstrated in 3/4 cell lines, in which the protein expression of p16 was lost. Methylation of RASSF1A was observed in 3/4 cell lines. Copy number gains of EGFR, HER2 or MET were not detected in the 4 cell lines. Mutations in various genes, including EGFR, KRAS, HER2, BRAF, and PIK3CA, which are frequently detected in non-small cell lung cancer, were not detected in the 4 cell lines. microRNA-34b/c is a direct transcriptional target of p53 and is often silenced in MPM by promoter methylation. In the present study, miR-34b/c was heavily methylated in 2/4 established MPM cell lines. For cell adhesion molecules, E-cadherin expression was detected in the 2 epithelioid MPM cell lines, whereas N-cadherin expression was detected in all 4 established cell lines by western blotting. Vimentin was strongly expressed in the 2 sarcomatoid MPM cell lines. None of the established MPM cell lines demonstrated significant responses to the drugs tested, including NVP-AUY922, 17-DMAG, Trichostatin A, and Vorinostat. Although novel molecular findings were not observed in the current characterization of these MPM cell lines, these lines will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies.