Cytotoxic impacts on the tumorigenesis and transplantability of ovarian teratoma in lt/sv mouse

The incidence and transplantability of ovarian teratoma in LT/Sv mice were examined following cisplatin treatment at the age of 16 days, and compared to those in the control group. Cisplatin had not affected the emergence of egg cleavage, which simultaneously appeared in the mouse ovaries in both groups. Although 7 teratomas, occasionally transplantable, developed in the control mice aged over 30 days, only 2 tumors occurred in cisplatin-treated mice at the age of 120 days and they were not transplantable. The results suggest that cisplatin might influence the tumorigenic process after egg cleavage, or transplantability of teratoma.     

On-line assessment of regional ventricular wall motion by transesophageal echocardiography with color kinesis during minimally invasive coronary artery bypass grafting

OBJECTIVE: Our objective was to determine the changes in regional ventricular wall motion during minimally invasive direct coronary artery bypass grafting by color kinesis using transesophageal echocardiography. METHODS: Minimally invasive coronary artery bypass grafting was performed in 34 patients, during which transesophageal echocardiography was used. Thirteen patients had isolated disease of the left anterior descending artery. Regional ventricular wall motion was analyzed by color kinesis with the SONOS 2500 transesophageal echocardiograph (Hewlett-Packard Co, Andover, Mass). On-line assessment of regional wall motion was continued during the operation. RESULTS: Wall motion abnormalities during ischemia were present in 4 cases, left ventricular mid-anterior hypokinesis in 3 cases, and left ventricular apical-lateral hypokinesis in 1 case. In all cases, wall motion was maintained after bypass. In patients with total coronary occlusion, changes in wall motion did not occur during anastomosis. CONCLUSIONS: Color kinesis allowed us to evaluate the change in regional ventricular wall motion induced by myocardial ischemia during minimally invasive coronary artery bypass grafting both objectively and quantitatively.     

Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer.

PURPOSE: The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non-small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression. EXPERIMENTAL DESIGN: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I-IIIA, NSCLC. RESULTS: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor. CONCLUSIONS: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC.     

Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels.

PURPOSE: There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker. EXPERIMENTAL DESIGN: Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value. RESULTS: The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II). CONCLUSIONS: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.     

Mechanistic Study of the Oxidative Degradation of the Triazole Antifungal Agent CS-758 in an Amorphous Form

In this study, the degradates generated from a pharmaceutical solid were characterized, and a mechanistic pathway underlying their formation was proposed. The chemical stability of a novel triazole antifungal drug, CS‐758, deteriorated significantly when the crystal was disordered, and characteristic degradates were generated. A total of eight degradates in solution and nine degradates in a solid state were isolated by preparative liquid chromatography. Degradates were characterized using high‐performance liquid chromatography–photodiode array, mass spectrometry, and nuclear magnetic resonance. Radical‐mediated oxidation is proposed as the main degradation pathway in the solid state. The initiation step of this pathway is hydrogen atom abstraction from a methine carbon that is adjacent to a dien moiety and the formation of a delocalized vinylic radical intermediate. Molecular oxygen is then added to the radical position to form hydroperoxides. There are three potential oxidation routes based on the proposed autoxidation pathway that lead to the generation of the dioxane ring‐opening hydroxyl form, the 9,10‐epoxide form, or the 11,12‐epoxide form, depending on the substituted position of the added molecular oxygen. The epimer compound generated via the vinylic radical intermediate and sulfoxides was characterized. This degradation mechanism provides the scientific foundation for an oxidative stressing system currently under investigation.     

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds.     

Frenum-like oral synechiae of the lip and vestibule

Two cases where aberrant tissue was attached to the lower lip mimicking the inferior labial frenum were reported. The frenum-like tissue extended from the gingival margin between the lower left deciduous central and lateral incisors in case 1 and between the lower right deciduous central and lateral incisors in case 2, to the dry lower lip. Histologically, the resected specimen was regarded as normal oral mucosa covered with stratified squamous epithelium, without a clear amniotic band. The frenum-like tissue of the lower lip found in both our patients was diagnosed as a category of oral synechiae, of unknown origin.     

Fluorescence visualization of the intersegmental plane by bronchoscopic instillation of indocyanine green into the targeted segmental bronchus: determination of the optimal settings

ObjectiveTo determine the appropriate amount of indocyanine green for bronchial insufflation.MethodsWe enrolled 20 consecutive patients scheduled for anatomical segmentectomy in the Kochi Medical School Hospital. After inducing general anesthesia, 6 to 60 mL of 200-fold-diluted indocyanine green (0.0125 mg/mL) was insufflated into the subsegmental bronchi in the targeted pulmonary segmental bronchus. The volume of the targeted pulmonary segments was calculated using preoperative computed tomography. Fluorescence spread in the segmental alveoli was visualized using a dedicated near-infrared thoracoscope.ResultsThe targeted segment was uniformly visualized by indocyanine green fluorescence in 16/20 (80.0%) cases after insufflating indocyanine green. A receiver operating characteristic curve indicated that the area under the curve was 0.984; the optimal cut-off volume of diluted indocyanine green for insufflation was 8.91% of the calculated targeted pulmonary segment volume.ConclusionsThe setting for indocyanine green insufflation was optimized for near-infrared fluorescence image-guided anatomical segmentectomy. By injecting the correct amount of indocyanine green, fluorescence-guided anatomical segmentation may be performed more appropriately.