Evaluation of the Therapeutic Effects of Harmine on Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid carcinoma (ATC) is an extremely difficult disease to tackle, with an overall patient survival of only a few months. The currently used therapeutic drugs, such as kinase inhibitors or immune checkpoint inhibitors, can prolong patient survival but fail to eradicate the tumor. In addition, the onset of drug resistance and adverse side-effects over time drastically reduce the chances of treatment. We recently showed that Twist1, a transcription factor involved in the epithelial mesenchymal transition (EMT), was strongly upregulated in ATC, and we wondered whether it might represent a therapeutic target in ATC patients. To investigate this hypothesis, the effects of harmine, a ß-carboline alkaloid shown to induce degradation of the Twist1 protein and to possess antitumoral activity in different cancer types, were evaluated on two ATC-derived cell lines, BHT-101 and CAL-62. The results obtained demonstrated that, in both cell lines, harmine reduced the level of Twist1 protein and reverted the EMT, as suggested by the augmentation of E-cadherin and decrease in fibronectin expression. The drug also inhibited cell proliferation and migration in a dose-dependent manner and significantly reduced the anchorage-independent growth of both ATC cell lines. Harmine was also capable of inducing apoptosis in BHT-101 cells, but not in CAL-62 ones. Finally, the activation of PI3K/Akt signaling, but not that of the MAPK, was drastically reduced in treated cells. Overall, these in vitro data suggest that harmine could represent a new therapeutic option for ATC treatment.

Nodular cutaneous metastasis of the leg in advanced urothelial bladder carcinoma: a case report and systematic literature review.

Cutaneous metastases from urothelial carcinoma (UC) are very rare and indicate advanced disease with a poor prognosis. A 63-year-old female patient with a history of urothelial bladder carcinoma, treated 2 months prior with radical cystectomy and adjuvant gemcitabine and cisplatin (GC) therapy, presented a skin lesion localized in the lower third of the right leg. Punch biopsy revealed carcinomatous metastasis whose urothelial origin was confirmed by immunohistochemical analysis. 18-FDG PET-CT showed the spread of metastases to the lung and left ischium. Our review focuses on the time between surgery and skin metastasis, localization, and prognosis after metastasis diagnosis. In many cases, skin metastases occur within one year of initial UC surgery and in most cases occur on the abdominal wall. Local wide excision of metastasis should be considered in selected cases; however, chemotherapy remains the main treatment.

Acute Cholecystitis from Biliary Lithiasis: Diagnosis, Management and Treatment.

Biliary lithiasis is a global disorder affecting nearly 20% of the world's population, although most cases occur without symptoms. Gallbladder stones could move into the common bile duct after gallbladder contraction, causing acute cholecystitis. The progression of the acute disease can take different forms, from mild inflammation, treatable with oral antibiotics, to the most severe forms with septic shock or biliary peritonitis, requiring specific treatment. Liver function tests and abdominal ultrasound are generally sufficient for diagnostic purposes. The most commonly used antibiotic is penicillin, with piperacillin achieving the best results; alternatively, fluoroquinolones could also be used, although there is no univocal consensus and surgery remains the only definitive treatment. A prolonged antibiotic therapy after cholecystectomy seems inadvisable, except in severe cases and/or in the immuno-compromised patient, where it should be periodically evaluated to avoid antibiotic resistance and unnecessary use. This review presents an evidence-based analysis to describe the advantages and disadvantages of the available options for the treatment of biliary lithiasis and cholecystitis, from the pathophysiological mechanisms behind lithiasis formation and also covering the main diagnostic findings for biliary stones, recommending an approach tailored to the patient's characteristics and to the team's expertise.

Poorly Differentiated Thyroid Carcinoma: Single Centre Experience and Review of the Literature.

There is controversy in the literature regarding a distinct subset of thyroid carcinoma whose histologically classification falls between well-differentiated and anaplastic carcinomas, previously identified as 'poorly differentiated thyroid carcinoma' (PDTC), or 'insular carcinoma', in view of the peculiar morphological characteristics of the cell groupings. The correct diagnosis and treatment of this entity have important prognostic and therapeutic significance. In this review, we describe the epidemiology, diagnosis, and management of PDTC and report our single centre experience to add to the limited evidence existing in the literature.