Expression of phosphatase of regenerating liver-3 (PRL-3) in endometrioid cancer and lymph nodes metastases

PurposeWe identify the expression of PRL-3 in primary endometrioid endometrial cancer and metastases in relation to the clinicopathological characteristics.Material/MethodsThe study involved 30 patients with type I endometrial cancer. Twelve of them were diagnosed with metastases in various localization of abdomen. The PRL-3 expression was evaluated on the basis of immunohistochemistry results by the use of monoclonal antibody anti-PRL3 clone 3B6.ResultsThe intensity of PRL-3 expression in correlation with tumor stage was statistically significant (p = 0.024). The strongest reaction was noted in cases classified as a 1a and 1b stage defined by FIGO. The strength of PRL-3 expression is significantly associated with the degree of histological tumor grade (p = 0.035).ConclusionsThe strong expression of PRL-3 in the primary tumor that was significantly correlated with the grade and clinical stage suggest that PTP4A3 participates in the process of endometrial carcinogenesis.     

Evaluation of fluorescent plasma markers for in vivo microscopy of the microcirculation

This study evaluated four fluorescent-protein conjugates to monitor microcirculatory variables using the murine cremaster muscle and determined acute and long-term responses to repeated administration of FITC-BSA [conjugated at the University of Sheffield (UoS)] within a dorsal microcirculatory chamber (DMC) in rats. For analysis of the cremaster muscle, male C3H/HeN mice were anaesthetized, the cremaster muscle was exteriorized, then TRITC-BSA, TRITC-dextran, FITC-BSA, FITC-BSA (UoS) or FITC-dextran (0.25 ml/100 g) were administered systemically. The microcirculation was viewed with epi-illumination every 10 min for 120 min. For analysis of the DMC, male Wistar rats were implanted with the chamber. Three weeks later, FITC-BSA (UoS) was administered systemically, and the microcirculation response was monitored using three different protocols. In addition, in vitro stability of fluorescent conjugates was measured over 8 h. With regard to the cremaster muscle, initially no differences in interstitial fluorescence or vessel diameter were observed between the four fluorescent conjugates. By the end of the study, interstitial fluorescence from TRITC-dextran, FITC-dextran and FITC-BSA (Sigma) was significantly (p < 0.05) increased compared to FITC-BSA (UoS). With regard to the DMC, there was no interstitial fluorescence leakage after 180 min or 5 weeks despite repeated administration, but a significant (p < 0.05) leak was detected between 4 and 24 h. FITC-BSA (UoS) was the most stable fluorescent conjugate both in vitro and in vivo and was comparable with other conjugates for evaluating skeletal muscle microcirculation using fluorescent in vivo microscopy.     

Pharmacological modulation of cardiac function and blood vessel calibre

Sympathomimetics such as noradrenaline, adrenaline and dopamine all have a positive inotropic effect and may be useful in treating different aspects of cardiovascular collapse. Digoxin, which inhibits the cardiac Na⁺/K⁺ adenosine triphosphatase pump and the phosphodiesterase III inhibitors milrinone and amironone, which both increase in cyclic adenosine monophosphate may also be useful for treatment of angina and heart failure respectively. The cardiac effects of β-blockers, L-type Ca²⁺ channel antagonists, K⁺ channel openers, I(f) inhibitors and nitrovasodilators and their role in angina are described in this article. The list of pharmacological control mechanisms that regulate the calibre of blood vessels is ever expanding and, for ease of understanding, they have been divided into neural, humoral and local mechanisms capable of inducing either vasodilation or vasoconstriction. Moment-to-moment sympathetic nerves and α₁ adrenoceptors maintain vascular tone but, locally, L-type Ca²⁺ channels (LTCC) also have an important function. LTCC antagonists inhibit influx at three sites on the α-subunit of the channel (dihydropyridine, phenylalkylamines and benzothiazepines) to alleviate hypertension. Inhibiting circulating hormones or the receptor targets for hormones, such as angiotensin-II or vasopressin may also be useful for the treatment of hypertension or shock. Nitric oxide (NO) is also one of the most important vasodilator local-control mechanisms, via stimulation of guanylyl cyclase and increased cyclic guanosine monophosphate, and this is counteracted by endothelin-1, one of the most potent vasoconstrictors, which, like NO, also has an important role in diseases such as sepsis.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.