Pentraxin 3 is an adipose tissue‐related serum marker for pancreatic cancer cachexia predicting subsequent muscle mass and visceral fat loss

Cancer cachexia, a paraneoplastic syndrome characterized by ongoing skeletal muscle mass loss, is accompanied by adipose tissue loss and strongly affects chemotherapy endurance. Our aim was to detect a serum marker reflecting pancreatic cancer cachexia and predicting subsequent loss of muscle mass and adipose tissue, focusing on adipose tissue‐secreted proteins. Murine‐derived pancreatic cancer cells were orthotopically injected into the mouse pancreatic tail. After 3 weeks, RNA sequencing of perigonadal fat and orthotopic tumors was carried out. We analyzed stocked sera and clinical data of metastatic pancreatic cancer patients who received chemotherapy. Perigonadal fat weight/body weight decreased in mice with orthotopic tumors compared to those without tumors. By RNA sequencing and real‐time PCR validation, pentraxin 3 (PTX3) was identified as a secreted protein‐encoded gene whose expression was significantly higher in the perigonadal fat of mice with orthotopic tumors than in that of mice without orthotopic tumors and was least expressed in orthotopic tumors. Serum PTX3 levels correlated with PTX3 mRNA levels in perigonadal fat and were higher in mice with orthotopic tumors than in those without tumors. In 84 patients diagnosed with metastatic pancreatic cancer, patients with high serum PTX3 levels showed a greater visceral fat loss/month and skeletal muscle mass index (SMI) decrease/month than those with low serum PTX3 levels. High serum PTX3 was an independent risk factor for visceral fat loss, decreased SMI, and poor prognosis. High serum PTX3 in pancreatic cancer patients predicts visceral fat and muscle mass loss and major clinical outcomes of cancer cachexia.     

Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer.

PURPOSE: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m(2) for VRB on days 1 and 8 and 4 mg/m(2) for MMC on day 1, with a fixed dose of P 80 mg/m(2) on day 1 every 4 weeks. MMC was increased to 6 mg/m(2) at dose level 2 and subsequently to 8 mg/m(2) at dose level 4. At dose level 3, VRB was increased to 25 mg/m(2). Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. RESULTS: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m(2) on days 1 and 8 and MMC 8 mg/m(2) and P 80 mg/m(2) on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in 相似文献   

Transfemoral closure of patent ductus arteriosus: An alternative to surgery in older patients

Two patients with congestive heart failure underwent successful closure of patent ductus arteriosus (PDA) at ages 58 and 63, respectively, using the transfemoral technique of Porstmann and Sato. The long-term benefits obtained in these two patients suggests a potential role for this technique in the elderly patient with PDA     

Sex Differences in o-Phenylphenol and Sodium o-Phenylphenate Rat Urinary Bladder Carcinogenesis: Urinary Metabolites and Electrolytes under Conditions of Aciduria and Alkalinuria

F344 male and female rats were administered 1.25% o -phenylphenol (OPP) or 2% sodium o- phenylphenate (Na-OPP) in combination with 3% NaHCO₃ or 1% NI₄Cl for 8 weeks and changes in the urinary bladder histopathology and the urinary components were examined. Administration of OPP with NaHCO₃ resulted in marked urothelial liyperplasia in the urinary bladder of male rats, the response being less pronounced in females. OPP alone exerted no proliferative effect and NaHCO₃ induced only slight hyperplasia in males. Na-OPP alone induced mild hyperplastic lesions only in males, this being completely prevented by concomitant administration of NH₄C1. The findings thus demonstrated a clear correlation between hyperplastic response and reported carcinogenic potential of these treatments. Of the urinary factors examined, increases in levels of pH and sodium ion concentration were positively associated with proliferative lesions especially in males, although the findings failed to explain the sex difference. Urinary concentrations of non-conjugated forms of OPP metabolites were also not directly correlated with the development of hyperplasias. Thus, changes in individual urinary factors presumably affect nrothelial proliferation in combination rather than separately. The presence of OPP metabolites, including 2-phenyl-l,4-benzoquinone, in the urine may be unimportant in the OPP urinary carcinogenesis even under conditions of alkalinuria and high sodium ion concentration.     

Critical appraisal of treatments in emergency settings]

A critical appraisal was carried out of treatment with high-dose epinephrine (HDE) in cardiopulmonary resuscitation (CPR), active compression and decompression CPR (ACD-CPR), military antishock trousers (MAST), and Continuous renal replacement therapy (CRRT) in the emergency setting, based on evidence-based medicine. Although the pathophysiological rationale encourage the clinical application of these treatments to improve the long-term outcome (mortality), no clinical trial could confirm their benefit. Additionally, Japanese investigators have reported no clinical epidemiological study related to this issue. Thus a clinicoepidemiological study associated with treatments in critical settings is required in this country.     

Long-term prognosis of patients with congestive heart failure

Factors determining prognosis in 100 patients with recent onset of congestive heart failure (CHF) were evaluated. The 1 year, 3 year, 5 year, and 10 year survival rates in the entire CHF group were 78.5%, 59.8%, 50.4% and 14.7%, respectively. No correlations between age, sex, heart rate and cardiothoracic ratio, and the cumulative survival rate were found. The prognosis of patients with CHF due to underlying coronary artery disease or primary cardiomyopathy was poor compared with that of patients with other types of heart disease. Patients whose NYHA classification was class III or VI had a significantly lower survival rate than those in class II. Patients with lower left ventricular stroke work and consecutive ventricular premature depolarization also had a significantly lower survival rate. These results suggest that functional status, underlying heart disease, left ventricular stroke work, and the presence of ventricular tachycardia provide important information regarding the long-term prognosis in patients with congestive heart failure.