Tumour expresion of tissue factor and tissue factor pathway inhibitor in ovarian cancer- relationship with venous thrombosis risk

Introduction

Ovarian cancer is known to display a particular association with venous thromboembolism (VTE) with reports up to 42% of patients developing thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of this study was to measure tumour derived TF and TFPI and to investigate their potential role in VTE in ovarian cancer patients.

Methods

TF and TFPI mRNA expression was measured using TaqMan real time PCR in 99 ovarian tumour samples. Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and TFPI protein levels were measured using ELISA and immunohistochemistry was used to localize TF expression. The role of TF expression on overall survival was also determined.

Results

TF mRNA and protein expression was increased in tumours from patients with clear cell carcinoma (p < 0.001). TF protein expression was also increased in endometroid carcinoma (P < 0.01) compared with benign tumours. TFPI mRNA expression was increased in clear cell carcinoma (P < 0.01). TF mRNA and antigen level was increased in malignant tumours of patients who developed VTE compared with matched malignant õtumours of patients who remained thrombosis free (P < 0.01). There was no difference in TFPI expression between the two groups.

Conclusion

TF expression in ovarian cancer is significantly higher in patients who develop VTE. TF expression was increased in clear cell ovarian cancer and endometroid cancer and this may explain the higher risk of VTE in these subgroups. TF derived from these tumours may be the trigger for VTE in ovarian cancer.     

Lack of androgenicity and estrogenicity of the three monomers used in Eastman’s Tritan™ copolyesters

Eastman Tritan™ copolyester, a novel plastic from Eastman is manufactured utilizing three monomers, di-methylterephthalate (DMT), 1,4-cyclohexanedimethanol (CHDM), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) in various ratios. As with most any polymer, the monomers along with the high molecular weight oligomers, whose toxicity is most commonly represented by the monomers, make up the predominate amount of free chemicals available for leaching into the environment and/or foods. In light of the high level of public concern about the presence of endocrine (primarily estrogenic) activity ascribed to certain plastics and chemicals in the environment, Tritan’s™ monomers were evaluated using QSAR for binding to the androgen receptor and estrogen receptors (alpha and beta) as well as a battery of in vitro and in vivo techniques to determine their potential androgenicity or estrogenicity. The findings were universally negative. When these data are coupled with other in vivo data developed to assess systemic toxicity and developmental and reproductive toxicity, the data clearly indicate that these monomers do not pose an androgenic or estrogenic risk to humans. Additional data presented also support such a conclusion for terephthalic acid (TPA). TPA is also a common polyester monomer and is the main mammalian metabolite formed from DMT.     

Hyperbaric oxygen for stroke treatment

ABSTRACT: This is an editorial for the inauguration of the Medical Gas Research and addresses a particular issue of using hyperbaric oxygen for stroke treatment.     

A single institution experience of streptozocin/fluorouracil combination chemotherapy: a case series

Background

The combination chemotherapy regimen of streptozocin and 5-fluorouracil (FU/STZ) has been used for the treatment of metastatic neuroendocrine tumours.

Aim

The aim of this study was to analyse the use of this regimen in a tertiary oncology referral centre over a 10-year period.

Method

We retrospectively analysed nine cases from February 2000 to May 2010. Patient demographics, chemotherapy schedule, toxicities, progression-free and overall survival were tabulated for each patient.

Result

The median progression-free survival was 17?months (range 3?C48+?months), and overall survival 31?months (range 12?C53+?months) with no toxicity related deaths.

Conclusion

FU/STZ was a well-tolerated regimen that produced significant benefit in the setting of metastatic and progressive disease. Our case series demonstrated comparable progression-free survival and overall survival in relation to randomized controlled studies and previous case series.     

Metastatic bone cancer pain: Etiology and treatment options

Painful metastatic bone disease remains a challenge for physicians. The treatment choices available are wide and varied, with each having its appropriate place in the management of painful bone metastases. Radiotherapy remains the mainstay of treatment with or without surgery. Advances in understanding the intricate pathway responsible for pain generation and the addition of agents such as bisphosphonates to the physician’s armamentarium further assist in the management of painful bone metastases.     

EMMPRIN-mediated MMP regulation in tumor and endothelial cells

Tumor invasion and metastasis are multistep processes which require extracellular matrix remodeling by proteolytic enzymes such as matrix metalloproteinases (MMPs). The production of these enzymes is stimulated by many soluble or cell-bound factors. Among these factors, extracellular matrix metalloproteinase inducer (EMMPRIN) is known to increase in vitro stromal cell production of MMP-1, MMP-2 and MMP-3. In this study, we demonstrated that EMMPRIN-transfected MDA-MB-436 tumor cells displayed a more invasive capacity than vector-transfected cells in a modified Boyden chamber invasion assay. Using gelatin zymography and protein analyses, we showed that EMMPRIN-transfected cancer cells produced significantly more latent and active MMP-2 and MMP-3 than vector-transfected cancer cells. We found that EMMPRIN did not regulate MMP-1, MMP-9, membrane type-1 MMP (MT1-MMP) expression and had also no effect on the production of the specific tissue inhibitors of MMPs (TIMPs), TIMP-1 and TIMP-2. We also demonstrated that tumor-derived EMMPRIN stimulated MMP-1, -2, and -3 without modification of MMP-9, MT1-MMP, TIMP-1 and TIMP-2 production in human umbilical vein endothelial cells (HUVEC). These data provide support for the role of EMMPRIN in tumor invasion, metastasis, and neoangiogenesis by stimulating extracellular matrix remodeling around tumor cell clusters, stroma, and blood vessels. This revised version was published online in July 2006 with corrections to the Cover Date.     

Evaluation of irritation and sensitisation of two 50 μg/day oestrogen patches

Objectives: To comparatively assess the irritation and sensitisation of the Estradot^® transdermal oestrogen patch, in healthy postmenopausal women, using the Menorest^® transdermal oestrogen patch, as a comparator. Methods: In an open-label, single-centre, randomised, active-treatment, within-patient controlled study, 208 healthy postmenopausal women, age range 40–70 years, received and completed simultaneous treatment with a 5 cm² (50 μg/day) oestradiol patch (Estradot) and a 14.5 cm² (50 μg/day) oestradiol patch (Menorest). The treatment was given for 72 h, then 96 h, for eight successive applications during an induction phase, and for 72 h during a challenge phase. There was a 14-day resting period between phases. Skin irritation (measured by erythema on a scale of 0–4), topical sensitisation, patch adherence and local skin reaction, were assessed and recorded immediately before or after removal of each patch, as appropriate. Results: Most patients experienced a significant difference in irritation with Menorest than with Estradot (P<0.0001) at the end of the induction phase. Patch loss was also significantly higher for Menorest as compared to Estradot (P=0.0253) at the end of the induction phase. Most incidences of erythema were classified as slight (score of 1), and there was no significant difference in the percentage of topical sensitisation, or in the incidence of local skin reactions between Estradot and Menorest. Patch loss was low for both systems. Conclusions: Estradot demonstrates reduced skin irritation, superior adhesion and a lower rate of patch loss compared to Menorest.