RNA dysregulation is a hallmark of most human cancers, including PDAC. We identify the RNA‐binding protein MEX3A as prognostic factor in PDAC. MEX3A regulates stability of transcripts for cell cycle proteins, such as CDK6, and promotes cell cycle progression and resistance to chemotherapeutic treatments.

After the use of surgical staplers had become widespread, the number of colonic postoperative stenoses was observed to have increased. Nevertheless, the clinical relevance of this observation is minimal since only 2-5% of the patients complain of chronic constipation or obstruction symptoms. In such cases medical therapy is somewhat troublesome, and surgical treatment always implies a major operation. Endoscopic dilation has proved to be a reliable, simple, and safe therapeutic alternative. Forty-two patients with evidence of stenosis of either colocolic or colorectal anastomosis underwent mechanical or pneumatic dilation in our unit: 19 patients with a temporary diverting stoma were dilated before the colostomy was removed; in the remaining 23 cases, treatment was given according to the patients' symptoms or because it was not possible to pass the anastomosis with an endoscope. The overall failure rate was 2.4%, and no morbidity or mortality was found. When the percentages of patients successfully treated in one session alone were compared (76.9% versus 51.8%), balloon dilation was found to be more effective than bougienage. In our opinion, endoscopic dilation represents the mainstay of treatment of colonic anastomotic strictures, with surgery being reserved for the rare failures, when recurrence of cancer should be suspected.

Colorectal and glioblastoma cancer stem‐like cells (CSCs) are essential for translational research. Cell line authentication by short tandem repeat (STR) profiling ensures reproducibility of results in oncology research. This technique enables to identify mislabeling or cross‐contamination of cell lines. In our study, we provide a reference dataset for a panel of colorectal and glioblastoma CSCs that allows authentication. Each cell line was entered into the cell Line Integrated Molecular Authentication database 2.1 to be compared to the STR profiles of 4485 tumor cell lines. This article also provides clinical data of patients from whom CSCs arose and data on the parent tumor stage and mutations. STR profiles and information of our CSCs are also available in the Cellosaurus database (ExPASy) as identified by unique research resource identifier codes.

Between November 1988 and July 1992 70 patients with radiolucent gall stones were treated with extracorporeal lithotripsy (ESL) and ursodeoxycholic acid (UDCA; mean (SD) dose 11-2 (1-9) mg/kg/day). Fifty three patients have been followed for one year. One week after lithotripsy, 30-6% had completely eliminated all stone fragments from the gall bladder and one year later 93*9% were free of stones. Three factors were considered important in achieving these results. 'Pulverisation' of the stone -that is, its fragmentation into echogenic dust (crystalline aggregates, some few hundred > in size) or particles similar to grains of sand, smaller than 1 mm in diameter, or both, is required. Secondly, dust and particles were rapidly eliminated, strongly suggesting a mechanical elimination process by physiological gall bladder contractions. Thirdly, there must be chemical dissolution with biliary acids. This therapeutic approach gave excellent results without causing any clinically relevant side effects. The first 20 patients who became free of stones after ESL were given oral bile acid maintenance treatment -300 mg/ day of UDCA at bedtime, for two years. All were asymptomatic and none had suffered a recurrence after two years. In four patients, crystalline aggregates, detected in gall bladder bile by ultrasound, were subsequently dissolved between one and three months after resuming a full dose regimen of UDCA. (Gut 1994; 35: 117-12 Results of studies on extracorporeal lithotripsy (ESL) of gall stones in which patients have been followed up for seven years have often proved to be unsatisfactory and at times discordant. Despite this we believe that ESL is an extremely effective method of treating gall stones and that these negative results may result from the following factors that are unrelated to the procedure: (1) Use of equipment developed for kidney stone dissolution and improperly adapted to gall stone treatment; (2) Use of shock waves that are too low in pressure and too few in number; (3) Therapeutic strategy tending towards stone fragmentation followed by chemical dissolution with bile acids lasting even long periods of time.This trial aimed to determine whether by perfecting the technique of biliary lithotripsy, the procedure would prove to be an effective method of treating gall stones. For this purpose it was necessary to verify:(1) Whether by using shock waves adequate in pressure and in number it would be possible to achieve 'pulverisation' of stones into crystalline aggregates or particles the size of grains of sand, or both.(2) Whether by achieving this pulverisation it would be possible to achieve safer and more rapid elimination of the resulting microfragments.(3) Eliminating stones followed by maintenance treatment while preserving the gall bladder would be sufficient to avoid stone recurrence. Methods PATIENTSBetween November 1988 and July 1992, 70 patients with radiolucent gall stones were treated with a lithotripter equipped with an underwater spark-gap for shock wave generation (Dornier MPL...

<b><i>Introduction:</i></b> Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-dependent pathways in pancreatic neuroendocrine neoplasms (PanNENs) underlies the introduction of the mTORC1 inhibitor everolimus as treatment of advanced progressive PanNENs. Although everolimus significantly increases progression-free survival, most patients acquire secondary resistance to the drug. This study aimed at identifying mechanisms involved in acquisition of resistance to everolimus. <b><i>Methods:</i></b> BON-1 and everolimus-resistant (ER) BON-1 cells were used as in vitro system of sensitivity and acquired resistance. Transcriptome changes occurring in BON-1 and ER-BON-1 were investigated by RNA sequencing and validated by quantitative PCR analysis. RNA extracted from patients’ biopsies was used to validate MYC upregulation. Drug screening and functional assays were performed using ER-BON-1 cells. Cell cycle progression was evaluated by FACS analysis. <b><i>Results:</i></b> Our results show that MYC overexpression is a key event in the development of secondary resistance to everolimus in PanNEN cell lines and in metastatic lesions from neuroendocrine neoplasm patients. MYC knockdown restored ER-BON-1 sensitivity to everolimus. Pharmacological inhibition of MYC mediated by the cyclin-dependent kinase inhibitor dinaciclib strongly reduced viability of ER-BON-1. Dinaciclib synergized with everolimus and inhibited ER-BON-1 cell cycle progression. <b><i>Discussion:</i></b> Our findings suggest that MYC upregulation drives the development of secondary resistance to everolimus in PanNENs and that its inhibition is an exploitable vulnerability. Indeed, our results indicate that combined treatments with cyclin-dependent kinase and mTOR inhibitors may counteract secondary resistance to everolimus in PanNENs and may pave the ground for new therapeutic regimens for these tumors.