Breast cancer is the leading cause of cancer and mortality in women worldwide. Recent studies have argued that there is a close relationship between lipid synthesis and cancer progression because some enzymes related to lipid synthesis are overexpressed in breast cancer tissues. However, lipid distribution in breast cancer tissues has not been investigated. We aimed to visualize phosphatidylcholines (PCs) and lysoPCs (LPCs) in human breast cancer tissues by performing matrix assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), which is a novel technique that enables the visualization of molecules comprehensively. Twenty-nine breast tissue samples were obtained during surgery and subjected to MALDI-IMS analysis. We evaluated the heterogeneity of the distribution of PCs and LPCs on the tissues. Three species [PC(32∶1), PC(34∶1), and PC(36∶1)] of PCs with 1 mono-unsaturated fatty acid chain and 1 saturated fatty acid chain (MUFA-PCs) and one [PC(34∶0)] of PCs with 2 saturated fatty acid chains (SFA-PC) were relatively localized in cancerous areas rather than the rest of the sections (named reference area). In addition, the LPCs did not show any biased distribution. The relative amounts of PC(36∶1) compared to PC(36∶0) and that of PC(36∶1) to LPC(18∶0) were significantly higher in the cancerous areas. The protein expression of stearoyl-CoA desaturase-1 (SCD1), which is a synthetic enzyme of MUFA, showed accumulation in the cancerous areas as observed by the results of immunohistochemical staining. The ratios were further analyzed considering the differences in expressions of the estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67. The ratios of the signal intensity of PC(36∶1) to that of PC(36∶0) was higher in the lesions with positive ER expression. The contribution of SCD1 and other enzymes to the formation of the observed phospholipid composition is discussed.

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Paraduodenal hernias have traditionally been treated by conventional laparotomy. We report the first case of a left paraduodenal hernia treated laparoscopically. A 44-year-old man was admitted with abdominal pain and nausea. Computed tomography and an upper gastrointestinal series with small-bowel followthrough showed accumulation of the small bowel on the left side of the abdomen. A laparoscopic repair was performed. The small bowel was observed beneath a thin hernia capsule. Approximately 1.5 m of jejunum was easily reduced into the abdominal cavity. The hernia orifice (5-cm diameter) was closed intracorporeally with five interrupted sutures. Good exposure of the operative field is critical to this procedure; poor exposure may limit the applicability of the laparoscopic approach. This minimally invasive operation is currently indicated in nonobstructive paraduodenal hernias, especially on the left.

As a new form of cigarettes, heated tobacco products (HTPs) have been rapidly distributed worldwide. In this study, an improved method for analyzing gaseous and particulate compounds generated from HTPs is described. Smoke is collected using a GF-CX572 sorbent cartridge with 300 mg of carbon molecular sieves, that is, Carboxen 572 (CX572), and a 9 mm glass-fiber filter (GF). After collection, the CX572 particles from the cartridge are transferred along with the GF and deposited into a vial containing two phases of carbon disulfide and methanol. The CX572 particles settle into the lower carbon disulfide phase, while nonpolar compounds are desorbed. After the sample is allowed to stand, the solution is slowly stirred. The two-phase mixture of carbon disulfide and methanol is combined into a homogeneous solution. Polar compounds are then desorbed, while the desorbed nonpolar compounds remain in solution. For the analysis of carbonyl compounds, an enriched 2,4-dinitrophenylhydrazine solution is added to a portion of the combined solution for derivatization and subsequent high-performance liquid chromatography analysis. For the analysis of volatile organic compounds and water, a portion of the combined solution is analyzed by gas chromatography-mass spectrometry or equipped with a thermal conductivity detector. By applying the proposed GF-CX572 one-cartridge method to the analysis of the mainstream smoke generated from HTPs and traditional cigarettes, several chemical compounds are detected, and the chemical composition of smoke is revealed. The GF-CX572 one-cartridge method can analyze gaseous and particulate chemical compounds from the HTP smoke by utilizing not only the entire puff volume but also one puff volume because the GF-CX-572 cartridge can be replaced with a new cartridge within 3 s. An overview of the chemicals generated from HTPs is obtained in detail by one-puff volume sampling. In addition, the generated chemical compounds strongly depend on the temperature of tobacco leaves in HTPs.

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Triple-negative breast cancer (TNBC) is one of the breast cancer subtype that displays a high risk of early recurrence and short overall survival. Improvement of the prognosis of patients with TNBC requires identifying a predictive factor of recurrence, which would make it possible to provide beneficial personalized treatment. However, no clinically reliable predictive factor is currently known. In this study, we investigated the predictive factor of recurrence in TNBC using matrix-assisted laser desorption/ionization-imaging mass spectrometry for lipid profiling of breast cancer specimens obtained from three and six patients with recurrent and non-recurrent TNBC, respectively. The signal for phosphatidylcholine (PC) (32:1) at m/z 732.5 was significantly higher in the recurrence group compared to the non-recurrence group (P = 0.024). PC (32:1) was more abundant in the cancer epithelial area than it was in the surrounding stroma, suggesting that abnormal lipid metabolism was associated with malignant transformation. Our results indicate PC (32:1) as a candidate predictive factor of TNBC recurrence. A future prospective study investigating whether personalized therapy based on PC (32:1) intensity improves the prognosis of patients with TNBC is recommended.

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e Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone acetyltransferase for forming the prereplicative complex (pre-RC) at the replication origin. Pre-RC formation is completed by loading of the MCM2-7 heterohexameric complex, which functions as a helicase in DNA replication. HBO1 recruited to the replication origin by CDT1 acetylates histone H4 to relax the chromatin conformation and facilitates loading of the MCM complex onto replication origins. However, the acetylation status and mechanism of regulation of histone H3 at replication origins remain elusive. HBO1 positively regulates cell proliferation under normal cell growth conditions. Whether HBO1 regulates proliferation in response to DNA damage is poorly understood. In this study, we demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were phosphorylated in an ATM/ATR DNA damage sensor-dependent manner after UV treatment. ATM/ATRdependently phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4 DDB2 . Replacement of endogenous HBO1 in Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV irradiation. Our findings demonstrate that HBO1 is one of the targets in the DNA damage checkpoint. These results show that ubiquitin-dependent control of the HBO1 protein contributes to cell survival during UV irradiation.T ight regulation of genome maintenance processes, including DNA repair, checkpoints, apoptosis, and cell cycle control, prevents DNA instability after DNA damage. Mammalian cells coordinately operate these systems for organism survival, in part through ataxia telangiectasia mutated (ATM) and ATM-and RAD3-related protein (ATR), two critical kinases that function as regulators of major checkpoint pathways. ATM is primarily activated by DNA double-strand breaks (DSBs) (1), and ATR is activated in response to inhibition of DNA replication (2). Activated ATM and ATR phosphorylate histone H2AX to recruit DNA repair proteins (3) and also checkpoint kinase 1 (Chk1) to suppress cell cycle progression (4, 5). Chk1 indirectly inhibits dephosphorylation of Tyr15 of cyclin-dependent kinase 2 (CDK2) (6) and CDC2 via Cdc25A degradation (7). ATM and ATR also phosphorylate the p53 tumor suppressor to increase its protein stability (8). p53 is a critical cellular factor that induces apoptosis genes (9) and the p21 CDK inhibitor gene (10, 11). Thus, substrates of ATM and ATR are involved in arresting the cell cycle, repairing DNA, and eliminating damaged cells by apoptosis.Histone acetyltransferase binding to ORC-1 (HBO1) was originally identified as an ORC1 binding protein (12) and acts as a cofactor in the prereplicative complex (pre-RC) (13). This histone acetyltransferase (HAT) associates with distinct complexes to acetylate histones H3 and H4 (14, 15). HBO1 is also involved in cell proliferation control through regulating the expression of multiple genes in the p53 pathway (16). A previous ...