Weekly paclitaxel administration and intraabdominal CBDCA injection possibly beneficial treatment for recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation--a case report

A 46-year-old woman who had received mastectomy for breast cancer 6 years earlier complained of abdominal distension. Computed tomography and ultrasonography revealed massive ascites and ovarian swelling of both sides. She was diagnosed as having primary ovarian cancer and peritoneal dissemination, and underwent a total hysterectomy as well as ovarectomy on both sides. After surgery, she received a sequential chemotherapy, ie, intraabdominal injection of carboplatin (CBDCA 300 mg/m2) and div administration of paclitaxel (PTX 180 mg/m2) as a standard regimen for advanced ovarian cancer. However, detailed histological examinations showed that the ovarian cancer had metastasized from her breast cancer. It is well-known that breast cancer easily metastasizes to the bone, liver, pleura and lymph node, but rarely to the ovarium or peritoneum when chemotherapy is conducted. Therefore, no standard therapy has been established for breast cancer metastasizing to the ovarium. Our patient received 4 cycles of weekly administration of PTX (PTX 80 mg/m2, 3 consecutive weeks, 1-week break), followed by oral administration of doxifluridine+anastrozole on an outpatient basis. No evidence of recurrence of breast cancer has been noted 1 year after surgery. This result suggests that weekly administration of PTX and intraabdominal injection of CBDCA might be beneficial in the treatment of recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation.     

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.     

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine

Follicular lymphoma (FL) shows co‐expression of B‐cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa‐associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10^down) GI‐FL. The diagnosis of CD10^down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10^down GI‐FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI‐FL and nodal FL when the analysis was confined to primary GI‐FL (55.2% vs 3.5%, P < 0.001). Compared to CD10⁺ GI‐FL, CD10^down GI‐FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10^down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa‐associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10^down GI‐FL, and an identical clone was found between CD10^down follicles and CD10⁺BCL2⁺ neoplastic follicles. In the diagnosis of cases with CD10^down BCL2⁺ follicles, careful examination with molecular studies should be carried out.     

Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters

PurposeWe have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.MethodsIntracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.ResultsBCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.ConclusionsBCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.     

Abdominal aortic calcification is associated with Fibrosis‐4 index and low body mass index in type 2 diabetes patients: A retrospective cross‐sectional study

Aims/IntroductionThis study aimed to clarify the nature of the relationship between the abdominal aortic calcification (AAC) grade and the presence of cardiovascular diseases, and determine factors related to AAC grade in people with type 2 diabetes mellitus.Materials and MethodsThis retrospective cross‐sectional study enrolled 264 inpatients with type 2 diabetes mellitus. The AAC score and length were measured using the lateral abdominal radiographs. Logistic regression models were used to assess the associations between AAC scores/lengths and the presence of coronary artery disease (CAD), cerebral infarction (CI) and peripheral artery disease (PAD). The correlation between AAC scores/lengths and other clinical factors were evaluated using linear regression models.ResultsThe AAC score was significantly correlated with prevalent CAD and CI independent of age and smoking, but not with the prevalence of PAD. AAC length was not significantly correlated with the presence of CAD, CI or PAD; however, the sample size was insufficient to conclude, probably due to low prevalence. Both the AAC score and length were correlated inversely with body mass index (BMI) and, with the Fibrosis‐4 (Fib‐4) index >2.67; these correlations were significant after adjusting for cardiovascular risk factors and BMI, although AAC was not associated with ultrasonography‐diagnosed fatty liver. There was a significant interaction between BMI and Fib‐4 index; lower BMI and Fib‐4 index >2.67 showed a synergistic association with high AAC grade.ConclusionsAAC score is associated with CAD and CI morbidity in participants with type 2 diabetes mellitus. Low BMI and Fib‐4 index >2.67 can be valuable indicators of AAC in people with type 2 diabetes mellitus.     

SARC-F scores can predict health status and daily activity in patients with idiopathic pulmonary fibrosis

BackgroundThe strength, assistance in walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) is widely used for screening sarcopenia. We aimed to examine the association of SARC-F scores with the measurements of quality of life and activity in patients with idiopathic pulmonary fibrosis (IPF).MethodsThis cross-sectional pilot study prospectively enrolled 54 patients with IPF who completed pulmonary function tests, the 6-min walk test, the chronic obstructive pulmonary disease assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Scale, and a daily step count. The daily step count was measured continuously for 7 consecutive days using a tri-axis accelerometer device.ResultsThe mean age was 73.6±7.9 years and the mean percent predicted forced vital capacity was 80.4%±15.6%. The median [interquartile range] SARC-F score, SGRQ total scores, and CAT scores were 2 [1–3.25], 28.8 [14.4–46.9], and 13 [7–22], respectively. SARC-F scores were correlated with the percent predicted forced vital capacity (r=−0.51, P<0.001), CAT score (r=0.57, P<0.001), SGRQ total score (r=0.77, P<0.001), Hospital Anxiety and Depression Scale anxiety score (r=0.31, P=0.025), and Hospital Anxiety and Depression Scale depression score (r=0.28, P=0.041). Linear regression analyses revealed that the 6-minute walk test (6MWT) (standardized β=0.33, P=0.011) and SARC-F score (standardized β=−0.39, P=0.005), but not the CAT score and SGRQ total score, were significant predictors for daily step count.ConclusionsSARC-F scores were correlated with health status and daily activity in patients with IPF. Further studies are warranted to validate the utility of the SARC-F in patients with IPF.     

Metal-free visible-light-induced hydroxy-perfluoroalkylation of conjugated olefins using enamine catalyst

We developed a simple and sustainable method for the hydroxy-perfluoroalkylation of electron-deficient conjugated olefins and styrenes. In this protcol, in situ generated enamine forms electron-donor–accepter (EDA) complexes with perfluoroalkyl iodide, and reaction proceed with visible-light irradiation. Tertiary amine also interacts with perfluoroalkyl iodide via halogen-bonding, promoting the perfluoroalkyl radical generation. This reaction does not require any transition-metal or photoredox catalyst, and gaseous oxygen is used as the green hydroxy source. Moreover, various commercially available substrates and perfluoroalkyl iodides were tolerated, affording the desired hydroxy-perfluoroalkylated products in good to moderate yields (>50 examples, up to 90%).

A sustainable, visible-light-induced hydroxy-perfluoroalkylation of electron-deficient olefins and styrenes catalyzed by ena mine were successfully developed.     

The effect of L-erythro-dihydroxyphenylserine injected into the lateral ventricle and the hypothalamus on the locomotor activity

The effect of dihydroxyphenylserine (DOPS) on locomotor activity was studied using the Animex activity meter. One microgram of L-erythro-DOPS, a precursor of d-noradrenaline, was injected into the lateral ventricle once a day for one week or into the anterior hypothalamic area (AHA) once. After the intraventricular injection, the total locomotor activity (from 8:00 p.m. to 8:00 a.m.) of the rats injected with DOPS was significantly less than that of the rats injected with an artificial cerebrospinal fluid (5-ion). Analysis of the locomotor activity in consecutive 2-hr periods showed that the activity of the DOPS group during the time intervals of 10 p.m.-12 a.m., 12 a.m.-2 a.m. and 2 a.m.-4 a.m. was significantly less than that of the control group. After injection of DOPS or 5-ion into AHA, the total activity of the DOPS group was significantly less than that of the control. Analysis of the activity of the DOPS group for each 2-hr period between 10 p.m.-4 a.m. was also significantly less than that of the control. On the basis of these findings, the effect of DOPS in the brain noradrenergic system are discussed.     

Two new isoflavanones from Erythrina costaricensis

Two new isoflavanones, 5,3′-dihydroxy-4′-methoxy-5′-(3-methyl-1,3-butadienyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (1) and 5,3′-dihydroxy-5′-(3-hydroxy-3-methyl-1-butenyl)-4′-methoxy-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (2), together with two known isoflavonoids, cristacarpin, and euchrenone b₁₀, were isolated from the stems of Erythrina costaricensis. Their structures were established on the basis of spectroscopic evidence. These new compounds are rare isoflavanones, possessing both a 2,2-dimethylpyran substituent and a prenyl analog. The antibacterial activities of 1 and 2 against the methicillin-resistant Staphylococcus aureus were examined.