Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

BACKGROUND: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells. METHODS: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels. RESULTS: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC(50)) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 μM and 100 μM. CONCLUSION: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells

The effects of pentoxifylline on bacterial translocation after intestinal obstruction.

Bacterial translocation (BT) occurs mainly in preseptic conditions such as intestinal obstruction, trauma, and burn, and the underlying mechanisms are still unclear. Pentoxifylline (PTX) is a derivative of methyl xanthine and has several beneficial effects in sepsis. We investigated the effects of PTX on a rat BT model. Simple intestinal obstruction (IO) was choosen to create high BT rates. Rats were divided in to five groups of 10 rats. Either 50 mg/kg PTX or placebo (3 mg/100 g saline) was administered subcutaneously following IO, either by single injection or twice with a 12-h interval. All rats were sacrificed 12 or 24 h after the procedure, and mesenteric lymph nodes (MLN), liver, and blood samples were obtained under aseptic conditions for bacterial cultures. The samples were obtained 12 h following IO in the first two groups, and the same samples were obtained 24 h after IO in last three groups. Groups IV and V were the PTX treatment groups. PTX was re-injected 12 h after IO only in group IV. As a result, BT rates in MLNs and liver were found to be significantly low, blood specimens remained sterile in PTX-pretreated and -treated rats, and BT rates were high in control groups and group V (once treatment late specimen group). We conclude that simple intestinal obstruction causes BT, and PTX reduces BT in rats with IO during the first 12-h period if PTX is given once immediately following IO. PTX reduces BT during the first 24-h after IO provided that is injected twice with a 12-h interval. More experimental studies are need to explain the exact mechanism of this beneficial effect

Effects of locally applied 5-fluorouracil on the prevention of postmastectomy seromas in a rat model

Backgrounds: Seroma formation is the most common complication following mastectomy and axillary dissection ( AD). Currently available interventions have aimed at obliterating dead space by inducing fibrosis and through various mechanical methods. Here, 5- fluorouracil ( 5- FU), used as a sclerosing agent for the prevention of seroma formation, was investigated in a rat mastectomy model. Methods: 20 rats were divided into two groups ( 5- FU and control). All rats underwent mastectomy and AD. Immediately following the operation, equal volumes of saline and 5- FU were administered under the surgical flaps. One week after the operation, seroma formation and wound- healing processes were evaluated using histopathological and biochemical investigations. Results: 5- FU did not act as a sclerosing agent, yet it was highly effective in preventing seroma formation. The intensity of acute inflammation, vascularity, as well as leukocyte and fibroblast infiltration, were significantly lower in the 5- FU group than the control; the tissue collagen fractions and total seroma collagen contents were found to be similar between the two groups. Conclusions: The mechanisms underlying seroma prevention by 5- FU are probably related to a decrease in the inflammation and angiogenesis rather than a local fibrotic process. Seroma formation may be due to a prolonged inflammatory phase of wound healing. Copyright (C) 2008 S. Karger AG, Basel

Extracorporeal shock-wave lithotripsy for retained common bile duct stones

Retained common bile duct stones (CBDS) become a challenging problem when percutaneous and endoscopic methods fail. Extracorporeal shock-wave lithotripsy (ESWL) is a noninvasive and effective treatment modality, and can be used as an alternative treatment of retained CBDS. We report our experience with 20 patients who had retained CBDS, using a second-generation electromagnetic lithotriptor. Thirteen patients who had cholecystectomy and common bile duct exploration, with stone extraction and T-tube drainage, were in the early postoperative period. Seven patients had undergone previous endoscopic sphincterotomy and nasobiliary drainage. Fourteen patients had only one ESWL session. Stone fragmentation rates were 100% and 57% in patients with T-tube and nasobiliary catheter, respectively. The overall stone fragmentation rate was 85% and complete stone clearance was achieved in all these patients (85%). Complications were mild and relatively infrequent (20%). There was no mortality. We conclude that ESWL for retained CBDS is a safe, effective and minimally-invasive treatment modality. ESWL should be considered as a significant alternative to surgery when endoscopic and percutaneous treatment modalities are not successful

Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis

Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear

Perforated solitary ulcer of the colon - Report of a case

PURPOSE: A patient with a solitary colonic ulcer had sudden onset of crampy abdominal pain, anorexia, fever, and vomiting, with signs of positive peritoneal irritation. METHODS: The diagnosis was proved by histopathologic examination of right hemicolectomy material. RESULTS: An emergency laparotomy, with right hemicolectomy and ileotransversostomy, gave complete relief from symptoms. The patient was still asymptomatic at the two-year follow-up, and control colonoscopic examinations performed at 6 and 18 months after the operation were normal. CONCLUSION: Preoperative diagnosis of perforated solitary colonic ulcers localized at the right hemicolon may mimic acute appendicitis, and intraoperative findings may mimic colonic carcinoma. If the preoperative diagnosis is not certain, right hemicolectomy and ileotransversostomy, with regular colonoscopic controls, is a safe procedure in the treatment and follow-up of these patients

Seroma prevention by using Corynebacterium parvum in a rat mastectomy model

Seroma formation is the most common complication after mastectomy and continues to be an important problem during the early postoperative period. Several surgical and medical methods have been developed to try to overcome this problem; however, so far none have been used successfully in the routine clinical practice. The aim of this study is to evaluate the effects of Corynebacterium parvum (CP) as a sclerosing agent in both prevention and treatment of seromas after mastectomy and axillary dissection in an animal model. Sixty female Sprague-Dawley rats underwent mastectomy and axillary dissection under general anaesthesia. Following surgery, the rats were treated in 1 of 3 ways. In the prevention group, 1 cm(3) (0.35 mg) CP solution was injected beneath the skin flap just before closure of the incision after mastectomy. In the treatment group, animals in which a seroma was formed, the fluid was aspirated, and 1 cm(3) CP solution was injected beneath the flap. In the control group, animals in which seromas formed, aspiration only was performed. The frequency of seroma for mation decreased when CP solution was injected immediately after the operation (p < 0.01). In addition, seroma formation was effectively treated by CP injection when compared with the control group (p < 0.05). CP was effective as a prophylactic agent in the prevention group and as a therapeutic agent in the treatment group in this experimental model. CP injection may be useful for the management of this problem in a clinical setting. Copyright (C) 2001 S. Karger AG, Basel

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

7,12-Dimethylbenz[ a] anthracene ( DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium ( Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA ( 12 mg). In the Se group, rats received 20 mu g Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA - Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA Se- treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA - Se- treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA