Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

Sleep Deprivation: Effects on Weight Loss and Weight Loss Maintenance

This narrative review presents the findings from intervention studies on the effects of sleep deprivation on eating habits, metabolic rate, and the hormones regulating metabolism, and discusses their relevance to weight loss efforts. Disturbed sleeping patterns lead to increased energy intake, partly from excessive snacking, mainly on foods high in fat and carbohydrates. The studies focused mainly on the effects of sleep duration, but also of sleep quality, on dietary intake during weight loss trials, and on weight loss maintenance. It is important to explore sleep routines that could enhance the efforts of obese and overweight people to lose weight, maintain their weight loss, and improve their overall health.     

Effect of deflazacort on cardiac and sternocleidomastoid muscles in Duchenne muscular dystrophy: A magnetic resonance imaging study

ObjectiveTo evaluate the involvement of cardiac and sternocleidomastoid muscles by magnetic resonance imaging (MRI) measurement of T2 relaxation time and the left ventricular systolic function in patients with Duchenne muscular dystrophy (DMD) on treatment with deflazacort and compare them with DMD patients without treatment.SubjectsSeventeen patients with DMD (aged 17–22 years) on treatment with deflazacort for at least 7 years and 17 boys with DMD of younger age (12–15 years) without steroid treatment. All patients were free of cardiac or respiratory symptoms and had normal ECG and Holter monitor examination.MethodsT2 relaxation time of the myocardium (H), left (SCM-L) and right sternocleidomastoid (SCM-R) muscles and left ventricular systolic function were evaluated by magnetic resonance imaging (MRI) in two groups of DMD patients. Myocardial and sternocleidomastoid muscles T2 relaxation time was calculated using 16 TEs (10–85 msec) and TR at least 2000 ms and T2 maps were created.ResultsDMD on deflazacort had higher T2 relaxation time values of the heart and of both sternocleidomastoid muscles (T2H median (range): 47 (41–48) vs. 33 (31–37) ms, p<0.001, T2 SCM-L median (range): 35 (30–37) vs. 23 (20–26) ms, p<0.001, T2 SCM-R median (range): 35 (32–37) vs. 23 (20–27) ms, p<0.001) and left ventricular systolic function (LVEDV median (range): 95 (75–120) vs. 90 (80–105) ml, p=0.03, LVESV median (range): 45 (38–55) vs. 47 (41–51) ml, p=0.81(NS), LVEF median (range): 53% (51–57) vs. 48% (42–51), p<0.001) compared to DMD without treatment.ConclusionsDMD patients on deflazacort are characterized by better preservation of the T2 relaxation time of myocardium and sternocleidomastoid muscles and better LV systolic function. The duration of this beneficial effect needs to be studied prospectively.     

Heparin affin regulatory peptide is a key player in prostate cancer cell growth and angiogenicity

BACKGROUND: The development and growth of human prostate cancer is mediated by many tumor cell-derived growth factors. Heparin affin regulatory peptide (HARP) seems to be involved in the progression of several tumors of diverse origin. In the present study, we sought to determine if HARP is implicated in human prostate cancer. METHODS: An antisense strategy for inhibition of HARP expression in the human prostate cancer cell line LNCaP was used to study the role of HARP on cancer cell growth, migration, and angiogenic potential in vitro and in vivo. RESULTS: Exogenous human recombinant HARP was mitogenic for LNCaP cells. By decreasing the expression of endogenous HARP, we found that HARP was essential for LNCaP cell migration, as well as anchorage-dependent and independent growth. Endothelial cell functions in vitro and blood vessel formation in vivo induced by LNCaP cells were also inhibited when HARP expression was diminished. CONCLUSIONS: HARP seems to act as an important regulator of diverse biological activities in human prostate cancer cells.     

Transforming growth factor-β1 in the urine of young children with urinary tract infection

Urinary tract infection (UTI) is a frequent cause of morbidity during the first years of life and may lead to renal insufficiency. Transforming growth factor-1 (TGF-) is both immunoregulatory and an important mediator of interstitial fibrosis. TGF- was detected in the urine of 52% of 48 children aged 1–24 months with a first episode of UTI (94% due to Escherichia coli) and no obstructive nephropathy compared with 0 of 20 healthy young children (P<0.001). TGF- was detected in the urine only during the early stage (<1 day) after initiation of treatment. It was detected more frequently (P=0.06) and in significantly higher concentrations (P=0.046) in children with a normal ^99m Tc-dimercaptosuccinic acid scan compared with those with abnormal scans performed 3–14 days after the diagnosis of UTI, suggesting a regulatory role in fibrogenesis and outcome of pyelonephritis in childhood.