Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Neurofibromatosis type 1 first presented as hypertensive crisis.

Neurofibromatosis type 1 (NF1) is known to cause vascular complications including stenotic and aneurysmal disease. Here, we report a case of a woman in her early 20s, who presented with unilateral facial nerve palsy and hypertensive crisis, and was later found to have multiple bilateral intrarenal microaneurysms along with classic cutaneous manifestations of NF1. A causal relationship between the pathophysiology of NF1 and the development of renal artery microaneurysm and hypertension is proposed in this case report.

Case series: Immune checkpoint inhibitor-induced transverse myelitis.

Introduction: Increasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their various complications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity. Cases: We describe four patients across three tertiary centers in Australia with ICI-induced transverse myelitis. Three patients had a diagnosis of stage III-IV melanoma treated with nivolumab and one patient had stage IV non-small cell lung cancer treated with pembrolizumab. All patients had longitudinally extensive transverse myelitis on magnetic resonance imaging (MRI) spine and clinical presentation was accompanied by inflammatory cerebrospinal fluid (CSF) findings. Half of our cohort had received spinal radiotherapy, with the areas of transverse myelitis extending beyond the level of previous radiation field. Inflammatory changes on neuroimaging did not extend to the brain parenchyma or caudal nerve roots, except for one case involving the conus medullaris. All patients received high dose glucocorticoids as first-line therapy, however the majority relapsed or had a refractory state (3/4) despite this, requiring escalation of their immunomodulation, with either induction intravenous immunoglobulin (IVIg) or plasmapheresis. Patients in our cohort who relapsed had a poorer outcome with more severe disability and reduced functional independence following resolution of their myelitis. Two patients had no progression of their malignancy and two patients had malignancy progression. Of the three patients who survived, two had resolution of their neurological symptoms and one remained symptomatic. Conclusion: We propose that prompt intensive immunomodulation is favored for patients with ICI-transverse myelitis in an attempt to reduce associated significant morbidity and mortality. Furthermore, there is a significant risk of relapse following cessation of immunomodulatory therapy. We suggest one treatment approach of IVMP and induction IVIg for all patients presenting with ICI-induced transverse myelitis based on such findings. With the increasing use of ICIs across oncology, further studies are required to explore this neurological phenomenon in greater detail to help establish management consensus guidelines.

One disease, two lives.

Because breast cancer risk increases with age and women in the United States continue to delay childbirth, the incidence of breast cancer during pregnancy will rise. About 10% of patients younger than age 40 diagnosed with breast cancer are pregnant. Historically, labor-delivery and oncology, the two spheres of clinical care, rarely overlapped. However, breast cancer occurs in about 1 in 3,000 pregnancies. Case studies suggest that the administration of chemotherapeutic agents during the second and third trimesters may be safe for the mother and fetus. Three specific case studies of pregnant women with cancer who received treatment are presented to identify the issues of cancer during pregnancy. Outcomes of infants who received chemotherapy in utero and associated nursing implications also are explored.