Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy

Background:

Primary endocrine therapy (PET) with aromatase inhibitors (AIs) is an option in elderly patients unfit for or unwilling to undergo surgery. We studied the outcome of patients treated with letrozole as PET.

Methods:

Patients with early oestrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours were excluded. Reasons for offering PET, response, survival, cause of death, time to initial and best response, fracture incidence, and late failure rates were studied.

Results:

In all, 104 patients received PET due to frailty (n=48), comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up was 56 months (4–106). Eighty-five cancers responded to letrozole (stable disease (SD, n=19), reduction in size (PR, n=42), and complete response ((CR), n=24)). Median survival was 51 months (4–103), time to initial response (PR/CR) 4.5 months (2–24), and time to best response 8.5 months (3–50). Letrozole was stopped in 25 patients due to progressive disease (n=19), side effects (n=5), and patient choice (n=1). Only 12 of 49 deaths were from breast cancer.

Conclusion:

Letrozole is a reasonable alternative in elderly women with early ER/PR-positive invasive breast cancer who are unfit or unwilling to undergo standard therapy.     

Laparoscopic management of drain-site incisional hernias following laparotomies--a simple suture technique

BACKGROUND: Herniation through drain sites is a rare but recognized complication of surgical drainage and are actually considered to be a type of incisional hernia. Incisional hernias form following surgery through the incision site or previous drain sites, or through laparoscopic trocar insertion sites. PATIENTS AND METHODS: In this paper, we present 13 such patients with incisional hernia of the main laparotomy wound and at the drain site, and 1 patient with an isolated drain-site hernia. A laparoscopic meshplasty with a simple suturing of the drain-site defect was performed. DISCUSSION: Incisional hernias are reported to occur in approximately 4%-10% of patients following open surgical procedures. There are several studies that have proven the efficacy of laparoscopic repair of incisional hernias, when compared to open procedures. The main predisposing factor regarding incisional hernias is probably the presence of a sepsis during the previous laparotomy, which was why the drainage tube was kept in the first place. CONCLUSIONS: The laparoscopic approach is useful for repairing the main incisional hernia, as well as drain-site hernias, simultaneously. We cut costs by avoiding tacking devices and use intracorporeal suturing instead.     

Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis

Background  

The sensitivity and specificity of 18S rRNA polymerase chain reaction (PCR) in the detection of fungal aetiology of microbial keratitis was determined in thirty patients with clinical diagnosis of microbial keratitis.     

Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts – in vitro

Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous environmental contaminant, is an established endocrine disruptor (ED). Increasing evidences indicate that some EDs interfere with osteoblast differentiation and function. In the present study, we investigated the effects of DEHP on the expression of cell cycle proteins, differentiation markers, Runx2 and its co-activator TAZ in osteoblasts derived from neonatal rat calvaria. A significant decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of DEHP (100 μM) after 24 h treatment. DEHP treatment caused a significant decrease in ALP mRNA. While DEHP treatment significantly decreased the TAZ at mRNA and protein levels, it decreased only the Runx2protein levels. Histochemical localization of ALP, collagen and mineralized nodules studied from cells treated with DEHP (10 and 100 μM) for 21 days revealed a drastic decrease in collagen, ALP and mineralization. In conclusion, DEHP affected differentiation of neonatal rat calvarial osteoblasts and mineralization of matrix secreted by these cells.     

The multiple faces of RAGE – opportunities for therapeutic intervention in aging and chronic disease

Introduction: This review focuses on the multi-ligand receptor of the immunoglobulin superfamily – receptor for advanced glycation endproducts (RAGE). The accumulation of the multiple ligands of RAGE in cellular stress milieux links RAGE to the pathobiology of chronic disease and natural aging.

Areas covered: In this review, we present a discussion on the ligands of RAGE and the implications of these ligand families in disease. We review the recent literature on the role of ligand–RAGE interaction in the consequences of natural aging; the macro- and microvascular complications of diabetes; obesity and insulin resistance; autoimmune disorders and chronic inflammation; and tumors and Alzheimer’s disease. We discuss the mechanisms of RAGE signaling through its intracellular binding effector molecule – the formin DIAPH1. Physicochemical evidence of how the RAGE cytoplasmic domain binds to the FH1 (formin homology 1) domain of DIAPH1, and the consequences thereof, are also reviewed.

Expert opinion: We discuss the modalities of RAGE antagonism currently in preclinical and clinical studies. Finally, we present the rationale behind potentially targeting the RAGE cytoplasmic domain–DIAPH1 interaction as a logical strategy for therapeutic intervention in the pathological settings of chronic diseases and aging wherein RAGE ligands accumulate and signal.     

Potent in vitro cytotoxic and antioxidant activity of Careya arborea bark extracts

Careya arborea is used in traditional medicine for the treatment of tumors and other ailments. The successive chloroform and ethyl acetate extracts and crude 50% methanol extract exhibited potent cytotoxicity against cancerous RD, HEp-2 and HeLa cell lines. They were found to be safe against the normal Vero cell line. The methanol and aqueous extracts possessed strong antioxidant activity against many oxidants in the in vitro antioxidant screening. The total phenol content of these extracts was found to be high. The results suggest strong cytotoxic and antioxidant properties and support the ethnomedical claims for the plant.     

A novel site-II directed glycoprotein estimation ELISA to aid rabies vaccine manufacture for veterinary and human use

Although the World Health Organization recommends the use of in vitro techniques to qualify rabies vaccine lot release, very limited proposals have been made to arrive at a harmonized approach for wide scale usage. The present study proposed and evaluated the use of a novel avidin–biotin ELISA as an alternative to these in vivo tests in rabies vaccine manufacture. This assay utilized a neutralizing pan reactive monoclonal antibody (mAb) reactive with the conserved site-II of the natively folded rabies glycoprotein. Linear regression analysis of the in vitro glycoprotein estimates with the in vivo potency values, showed a good correlation (r² = 0.8) with veterinary vaccines, but a poor correlation (r² = 0.2) with human vaccines. However, we could qualitatively arrive at cut-off glycoprotein estimates from the ELISA, above which all the vaccines were declared to be protective by mouse challenge studies (>2.5 IU/dose).     

Long circulating PEGylated poly(d,l-lactide-co-glycolide) nanoparticulate delivery of Docetaxel to solid tumors

Purpose: The aim of this study was to investigate the ability of PEGylated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) to deliver Docetaxel (DTX) (an anticancer agent) to solid tumors.

Methods: PLGA–mPEG diblock copolymers were synthesized by ring opening polymerization reaction and characterized by ¹H NMR, FT-IR and gel permeation chromatography. NPs, with a smooth spherical shape and near 100 nm size were prepared using the emulsion solvent evaporation technique and characterized. The drug release rate was investigated in acidic and physiological media (phosphate buffer saline, pH 5.0 and 7.4). The therapeutic efficacy and biocompatibility of NP formulations were evaluated for in vitro cytotoxicity by MTT assay using MCF-7 and C26 cell lines. The pharmacokinetic and biodistribution studies were performed on C26 tumor bearing mice. The antitumor efficacy of DTX NP formulations on C26 tumor bearing mice was investigated.

Results: DTX-loaded PEGylated NPs increased the drug's biological half-life while providing substantial accumulation at the solid tumors. PEGylated NPs appear to be a promising alternate carrier for DTX having greater efficacy in inhibiting tumor growth.     

Preventive action of food seasoning spices mixture on fructose-induced lipid abnormalities

High fructose feeding in rats induces insulin resistance, hyperinsulinemia, hyperglycemia and dyslipidemia. The present study was undertaken to determine the hypolipidemic effect of food seasoning spices mixture on fructose-fed insulin resistant rats. Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the spices mixture at three different doses (10 mg, 30 mg or 50 mg/day/rat) orally 15 days later. At the end of 45 days of the experimental period fructose-fed rats displayed elevated plasma glucose and insulin levels and dyslipidemia which included elevated levels of cholesterol, triglycerides, free fatty acids, reduced high density lipoprotein cholesterol and increased very low density lipoprotein cholesterol. Alterations in tissue lipid levels were also observed. Simultaneous treatment with spices mixture along with fructose diet resulted in the normalization of plasma glucose and insulin levels and restoration of lipid levels in plasma and tissues. The insulin potentiating action of the active principles in these spices may contribute to the hypolipidemic effect of spices mixture in high fructose-fed rats.