High rate of hematological responses to sorafenib in FLT3‐ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation

Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3‐ITD‐positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off‐label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post‐transplantation FLT3‐ITD‐positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand‐foot syndrome. None of the patients developed graft‐vs.‐host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T‐cell infusions. Six patients are alive and in remission at the last follow‐up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3‐ITD‐positive post‐transplantation relapses, manageable also in combination with other therapeutic strategies.     

Melanocytic Nevi in Children of Southern Italy: Dermoscopic,Constitutional, and Environmental Factors

The objective was to estimate the prevalence of melanocytic nevi (MN) in children and to determine their dermoscopic characteristics and relationship with anatomic location and environmental and constitutional factors. The population was a randomly selected sample of 144 children who attended primary schools in Naples, Italy. Before physical examination of the children, standardized interviews were conducted with their parents. Follow‐up interviews of both the children and parents were conducted 1 year later. Photographic and dermoscopic images were obtained. Boys had more MN than girls; 465 MN (55.6%) were observed in boys and 371 (44.4%) in girls (p < 0.05). The trunk and neck were the most common locations of MN (p < 0.001). The main dermoscopic feature of all MN observed was a globular pattern (p < 0.001). A significant correlation between duration of sunbathing and MN counts was revealed (p < 0.05). At 1‐year follow‐up, 118 new MN were identified in 66 children. The trunk and neck areas were the most common regions involved in the appearance of new MN (n = 68, 57.6% of all new MN, p < 0.001). The new MN count was significantly higher in children who reported more sunbathing (p < 0.001). Changes in the dermoscopic pattern were observed in 45 persistent MN, demonstrating more MN with a reticular‐globular pattern, especially on the trunk, neck, and upper extremities (p < 0.001). MN development in early life is the result of complicated relationships between nevus evolution, anatomic location, and environmental and constitutional factors.     

Immediate implant placement and provisionalization of maxillary anterior single implants

An inevitable loss of soft and hard tissue after tooth extraction often results in a compromised site for anterior implant esthetics in both vertical and horizontal dimensions. Immediate implant placement and provisionalization has been a viable option for replacing failing maxillary anterior teeth as it preserves the vertical existing osseous and gingival architecture. With the simultaneous addition of soft‐ and hard‐tissue grafts, the peri‐implant horizontal tissue topography can also be maintained. The esthetic success of immediate implant placement and provisionalization procedures is influenced by a number of factors that can be identified as patient‐dependent or clinician‐dependent. This article describes in detail the process of patient selection, indications, contraindications, diagnosis, treatment planning and treatment execution required to achieve functional and esthetic success with immediate implant placement and provisionalization.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism