Refractory hypokalemia caused by cetuximab with advanced colorectal cancer patients: the case series and literature review.

Cetuximab is the first-line treatment for advanced metastatic colon cancer. But cetuximab can cause electrolyte disturbances, including hypomagnesemia and hypokalemia. Among them, hypokalemia is often caused by hypomagnesemia, not directly caused by cetuximab. This article reports two cases of refractory hypokalemia caused by cetuximab without hypomagnesemia. The two patients had no abnormalities in serum potassium before cetuximab treatment. The occurrence of hypokalemia was clearly correlated with the cetuximab, and they were significantly improved after stopping or reducing the dose. At the same time, the appearance of hypokalemia is significantly related to the efficacy of cetuximab. They have received 37 and 35 cycles of cetuximab-related therapy, with condition stable periods of 12.8 and 15.1 months, respectively. Obviously, our report refutes the above view. In our opinion, hypokalemia, a side effect of cetuximab, may be directly caused by it, rather than secondary to hypomagnesemia. Similar to hypomagnesemia, the appearance of hypokalemia often indicates a better curative effect of cetuximab.

N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis.

Accumulating evidence indicates that RNA methylation at N6-methyladenosine (m6A) plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers. However, little is known whether and how m6A-modification impacts long non-coding RNA (lncRNA) and lncRNA-mediated tumorigenesis, particularly in pancreatic ductal adenocarcinoma (PDAC). In the present study, we report that a previously uncharacterized lncRNA, LINC00901, promotes pancreatic cancer cell growth and invasion and moreover, LINC00901 is subject to m6A modification which regulates its expression. In this regard, YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level. Notably, two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1. Finally, RNA sequencing (RNA-seq) and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability. Together, our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.

Kunitz-type trypsin inhibitor with high stability from Spinacia oleracea L. seeds.

The trypsin inhibitor SOTI was isolated from Spinacia oleracea L. seeds through ammonium sulfate precipitation, Sepharose 4B-trypsin affinity chromatography, and Sephadex G-75 chromatography. This typical Kunitz inhibitor showed remarkable stability to heat, pH, and denaturant. It retained 80% of its activity against trypsin after boiling for 20 min, and more than 90% activity when treated with 6 M guanidine hydrochloride. The formation of stable SOTI-trypsin complex (K(i) = 2.3x10(-6) M) is consistent with significant inhibitory activity of SOTI against trypsin-like proteinases present in the larval midgut of Pieris rapae. Sequences of SOTI fragments showed homology with other inhibitors.

A trypsin inhibitor from Cassia obtusifolia seeds: isolation, characterization and activity against Pieris rapae.

A trypsin inhibitor was isolated from Cassia obtusifolia by ammonium sulfate precipitation, Sepharose 4B-trypsin affinity and Sephadex G-75 chromatography. The inhibitor consisted of a single polypeptide chain with a molecular mass of 19, 812.55 Da. It was stable from pH 2 to 12 for 24 h, whereas it was unstable either above 70 degrees C for 10 min or under reduced conditions. The inhibitor, which inhibited trypsin activity with an apparent Ki of 0.3 microM, had one reactive site involving a lysine residue. The native inhibitor was resistant to pepsin digestion, whereas the heated inhibitor produced 40% degree of susceptibility. The disulfide linkage and lysine residue were important in maintaining its conformation. Partial amino acid sequence of the purified protein showed a high degree of homology with various members of the Kunitz inhibitor family. Moreover, the inhibitor showed significant inhibitory activity against trypsin-like proteases present in the larval midgut on Pieris rapae and could suppress the growth of larvae.