Transforming growth factor-β enhances adhesion of melanoma cells to the endothelium in vitro

Melanoma invasion requires migration through the vascular barrier. An early event in this process is the adhesion of metastatic cells to the endothelium. To elucidate the role of TGF-β in the regulation of this process, human melanoma SK-MEL24 cells were labelled with [5′-³H]-thymidine and co-cultured with bovine pulmonary artery endothelial-cell monolayers. Radioactivity was assumed to be proportional to the number of SK-MEL24 cells bound to the endothelium. A low number of melanoma cells adhered to endothelial cells in a time-related manner. Pretreatment for 24 hr with 0.001 to 10 ng/ml TGF-β₁ or TGF-β₂ of both cell types enhanced melanoma-endothelium adhesion in a dose-dependent manner. Both melanoma and endothelial cells expressed RI- and RII-type TGF-β receptors. The effect of TGF-β was abolished by co-incubation with the proteoglycan decorin. Conditioned media from melanoma-endothelium co-cultures contained latent TGF-β and failed to affect cell-cell adhesion. However, activation of TGF-β by heating the medium or reducing the pH, increased melanoma-endothelium adhesion to an extent similar to that of the TGF-β administered to the cultures. Zimography demonstrated that both cell types expressed urokinase-type plasminogen activator (uPA). Addition of plasminogen to the co-cultures, which was likely to be activated to plasmin by uPA, resulted in activation of TGF-β and parallel stimulation of melanoma-endothelium adhesion. In conclusion, TGF-β may enhance adhesion of melanoma cells to the endothelium, playing a relevant autocrine/paracrine role in the progression of invasive melanoma. Int. J. Cancer 72:1013–1020, 1997. © 1997 Wiley-Liss, Inc.     

A 67 kDa non-hormone binding estradiol receptor is present in human mammary cancers

The presence of large amounts of a 67 kDa estradiol receptor that does not bind hormone was observed in 8 of 37 human mammary tumors (34 malignant and 3 benign). This form of receptor was detected by its conversion to hormone binding receptor by an endogenous tyrosine kinase in vitro. All 8 tumors were malignant. In these, the incubation of cytosol with ATP was seen to cause a 1- to 5-fold increase in estradiol-specific binding sites. These sites bound estradiol with physiological affinity, and their appearance was associated with tyrosine phosphorylation of estradiol receptor. The enzyme converting the non-hormone binding receptor into the hormone binding receptor is largely present in cytosol and scarce in membranes. It has been extensively purified. It is a 67 kDa protein under denaturating conditions, binds calmodulin-Sepharose in a Ca²⁺-dependent manner, is stimulated by Ca²⁺ and calmodulin, phosphorylates exogenous actin, is activated by the estradiol-receptor complex. The enzyme interacts with antibodies directed against the carboxy-terminal and catalytic domains of c-src. Therefore, it is a putative new member of the large c-src-related kinase family. Human mammary cancers with significant amounts of 67 kDa non-hormone binding receptor show relatively low levels of hormone binding estradiol receptor. The presence of non-hormone binding receptor that can be activated by in vitro tyrosine phosphorylation suggests that functional interaction of estradiol receptor with tyrosine kinases is altered in malignant tumors and has bearing on loss of hormone dependence and progression of the mammary cancer malignancy. © 1996 Wiley-Liss, Inc.     

Retinal Image Slip Must Pass the Threshold for Human Vestibulo-Ocular Reflex Adaptation

Journal of the Association for Research in Otolaryngology - We sought to determine whether repeated vestibulo-ocular reflex (VOR) adaptation training to increase the VOR gain (eye/head velocity)...     

VOR adaptation training and retention in a patient with profound bilateral vestibular hypofunction

A novel training method known as incremental VOR adaptation (IVA) can improve the vestibulo‐ocular reflex (VOR) gain for both active and passive head rotation by coupling active head rotations with a laser‐projected target that moves in the opposite direction of the head at a fraction of the head velocity. A 51‐year‐old male with bilateral vestibular hypofunction participated in a research protocol using a portable IVA device for 645 days. Passive VOR gains improved 179% to 600%; standing posture and gait also improved. Motor learning within the vestibular system using the IVA method is possible after severe vestibular pathology. Laryngoscope, 129:2568–2573, 2019     

Diabetes and erectile dysfunction: The relationships with health literacy,treatment adherence,unrealistic optimism,and glycaemic control

Purpose

The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM.

Materials and Methods

This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence.

Results

Overall, mean age was 62.5 ± 9.4 years (range: 20–75) and mean BMI was 28.4 ± 4.8 kg/m² (range: 18.4–46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5–25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i.

Conclusions

This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism.