Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer

Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

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.     

Relation between the insulin lowering rate and changes in bone mineral density: Analysis among subtypes of type 1 diabetes mellitus

Aims/IntroductionThe bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F).MethodsThis was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck.ResultsThe lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P < 0.01), with a similar tendency between the fulminant and slowly progressive subtypes.ConclusionsAmong the type 1 diabetes mellitus subtypes, bone mineral density undergoes time‐dependent changes, which reveals that the bone mineral density decline follows the impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and bone mineral density.     

Effect of amount of water in dispersed phase on drug release characteristics of dextran microspheres prepared by emulsion-solvent evaporation process

Microspheres containing theophylline (TH) were prepared from a hydrophobic dextran derivative by emulsion solvent evaporation method. The objective of this study was to evaluate the effects of poor solvent in dispersed phase on the particle properties and drug release characteristics of the microspheres. Mixtures of acetone and water were used as the dispersed phase and liquid paraffin as the continuous phase. The amount of water (poor solvent for polymer) was varied from 0.5 to 2 ml in 15 ml of dispersed phase. Drug release from the microspheres was examined using JPXIV 1st Fluid (pH 1.2) containing 0.02% Tween 20, and their structure was analyzed by scanning electron microscopy (SEM). The drug release behaviors were greatly affected by the amount of water. The percentage released until 8 h were 89% and 23% for 0.5 and 2.0 ml of water, respectively. The release mechanism shifted from Fickian diffusion to zero-order transport as the amount of water increased. According to SEM observations, TH was uniformly distributed over the entire microsphere prepared using 0.5 ml of water, and existed in the center of the microsphere, having a core-shell structure, when prepared using 2 ml of water. The amount of poor solvent in the dispersed phase was found to be a crucial factor determining the internal structure of microspheres and drug release characteristics.     

Usefulness of coronary angioscopy for the evaluation of hyperlipidemia

Hyperlipidemia is one of the major coronary risk factors, which leading to the clinical worse outcome in patients with coronary artery disease, that is, acute coronary syndrome. Coronary plaque rupture followed by the formation of thrombus has been revealed to be a major cause of acute coronary syndrome. It would be important to detect the vulnerable plaque before its rupture, but there were no ways to detect by the conventional methods except coronary angioscopy. Yellow plaque and thrombus are mostly observed at the culprit lesion by the coronary angioscopy, which suggests that vulnerable plaque is dark yellow. Coronary angioscopy may diagnose the high-risk group among patients with hyperlipidemia.     

Fatty liver with metabolic disorder,such as metabolic dysfunction‐associated fatty liver disease,indicates high risk for developing diabetes mellitus

IntroductionNonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction‐associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM.Materials and MethodsWe retrospectively assessed 9,459 participants who underwent two or more annual health check‐ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non‐overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants).ResultsThe DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre‐diabetes (P < 0.01).ConclusionsFatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.