Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma.

In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia's therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction.

Chronic renal failure, diabetes mellitus type-II, and gestation: an overwhelming combination.

This case report highlights on a child-bearer with chronic renal failure and diabetes mellitus type-II. Chronic renal failure (CRF) with diabetes mellitus (DM) type I in gestation is a rare case of a high-risk pregnancy. What is of significance though in this gestation, is that conception was achieved with the patient treated by a dialysis program. Furthermore, neither hypertension nor intrauterine growth restriction (IUGR) were detected and the patient was normotensive throughout gestation with no clinical signs of anemia. Strict and frequent application of the dialysis programs eradicates the uremic intrauterine environment, reduces the amniotic fluid volume, eliminates the chances of uterine rupture, leads to a longer gestation, increases the newborn's birth weight, and offers an optimal fetal survival rate; this is of note mainly in patients with cesarean sections reported in their medical history. To eliminate the complications of a premature delivery, the present authors had to find the right time point to give birth to this baby taking into account lung maturity, amniotic fluid volume, and preservation of the anatomical uterine integrity.

Pre-eclampsia and the vascular endothelial growth factor: a new aspect.

Pre-eclampsia (PE) is a multi-system disorder of human gestation characterized by hypertension, proteinuria, and edema, which resolves with placental delivery. This disease affects 3-14% of all pregnancies worldwide and 5-8% in the USA. Furthermore PE remains one of the leading causes of maternal and neonatal mortality and morbidity worldwide. One of the most important goals in obstetrics is the early identification of the patient with an increased risk for PE. This paper unifies the essential and validated findings of past and current scientific investigation which encompass the relationship between PE and the vascular endothelial growth factor (VEGF). VEGF and its receptors have acquired great interest due to their vital role in neovascularization (vasculogenesis and angiogenesis) in a variety of physical and pathological processes such as the female reproductive cycle, PE, and tumorigenesis. VEGF is secreted in response to tissue hypoxia and endothelial cell damage. Alterations in the circulating levels of this factor may therefore identify those pregnancies with a high possibility of developing PE. This review will summarize the present authors' current understanding of the role of circulating VEGF in the pathogenesis, clinical diagnosis, and prediction of PE.

MiRNAs: regulators of human disease.

MicroRNAs (miRNAs) represent the mediators of important leading biological functions of molecular pathways in humans. They are a class of very small, non-coding RNAs; their function is the balance of the protein levels at the post-transcriptional stage. They are implicated in molecular processes and diseases, including diabetes, metabolism, autoimmune diseases, angiogenesis and tumorigenesis, and female fertility, exhibiting an altered expression profile. Any process taking place in the human organism is intertwined by miRNAs. MiRNAs have an impact on the biochemistry of pathways of the invisible molecular world. They circulate in a stable chemical configuration in body fluids (tears, serum, plasma, amniotic fluid, ascetic fluid, urine) with their molecular sequence specificity remaining unchanged. Their indisputable molecular stability ranks them as extremely vigorous potential markers in human disease. MiRNAs demonstrate a specific expressive signature, representative of the tissue specificity and the clinical staging. The shift on the concentration and expression of a miRNA reflects the course of a disease. MiRNAs may operate as oncogenes (tumor growth) or tumor suppressor (tumor reduction) genes in cancer pathways. In malignant disease, proliferation, maintenance, and progression of cancer cells is induced by the stimulation of the oncogenes or complete deactivation of the tumor suppressor gene activity.

Immature malignant sacrococcygeal teratoma: case report and review of the literature.

Immature malignant sacrococcygeal teratoma (SCT) is a rare tumor, deriving from the three germinal layers and is found in the sacrococcygeal region. It is the most frequent site of teratomas in the fetus. A nut-brown, solid tumor with cystic areas with a ten-cm diameter is reported in the sacrococcygeal region of a female fetus of 23 weeks and with a weight of 308 g. The ultrasound and pathology evaluations revealed characteristics of an immature malignant SCT. The incidence of this tumor type is one in 35,000 to 40,000 live births and females are four times more likely to be affected than males. Sacrococcygeal and cervical teratomas can be diagnosed by prenatal ultrasound and magnetic resonance imaging (MRI). Teratomas are considered an interesting field for research.

Vanishing twins in diamniotic dichorionic in vitro fertilization gestation in mid-second trimester.

The authors report a diamniotic dichorionic twin pregnancy after in vitro fertilization (IVF) in mid-second trimester. The dead fetuses were delivered by cesarean section at the 20th week of gestation. The authors discuss management aspects and review of the literature.

Ultrasound diagnosis of recurring Jeune's syndrome: a case report.

Jeune's Syndrome or asphyxiating thoracic dystrophy (ATD) is a rare autosomal recessive skeletal dysplasia syndrome characterized by a small and narrow chest, short extremities, and often polydactyly associated with multiple organ manifestations. The severity of complications ranges from mild to lethal. This is a report of two cases of ATD diagnosed in successive pregnancies of a nonconsanguineous couple. The contribution of sonography in prenatal diagnosis of the syndrome is highlighted.

Missing ductus venosus: a case report.

BACKGROUND: The ductus venosus is a short vessel, present in the newborn infant on the dorsal surface of the liver, connecting the portal and umbilical circulation with the inferior vena cava. Agenesis of the duct is a rare anomaly. CASE: A 28-year-old woman was referred to our department for the first trimester ultrasound evaluation. Detailed scanning revealed agenesis of the duct. Fetal echocardiography showed cardiac disproportion at the level of the ventricles. CONCLUSION: Agenesis of the duct can be related to either cardiac or congenital abnormalities.

The challenging trisomy 16: a case report.

BACKGROUND: Trisomy 16 is a very frequent autosomal anomaly accounting for about 2% of first trimester abortions. In most pregnancies the chromosomal genome found in the fetus is also present in the placenta. Confined placental mosaicism is frequently detected in the placental region along with a structurally normal fetus. CASE: We present the case of a 39-year-old primigravida with confined placental mosaicism diagnosed with chorionic villus sampling. Amniocentesis showed a normal karyotype (46, XX). Detailed scanning revealed no structural fetal anomalies, but severe oligohydramnios. CONCLUSION: Diagnosis of trisomy 16 does not necessarily mean that the newborn has anatomical abnormalities.