Ellagic acid,extracted from Sanguisorba officinalis,induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells

In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA‐induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA‐induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy.     

Feeding jejunostomy following esophagectomy may increase the occurrence of postoperative small bowel obstruction

This study aimed to clarify the characteristics and treatment of bowel obstruction associated with feeding jejunostomy in patients who underwent esophagectomy for esophageal cancer. In this single-center retrospective study, 363 patients underwent esophagectomy with mediastinal lymph node dissection for esophageal cancer at the Wakayama Medical University Hospital between January 2014 and June 2021. All patients who underwent esophagectomy routinely underwent feeding jejunostomy or gastrostomy. Feeding jejunostomy was used in the cases of gastric tube reconstruction through the posterior mediastinal route or colon reconstruction, while feeding gastrostomy was used in cases of retrosternal route gastric tube reconstruction. Nasogastric feeding tubes and round ligament technique were not used. Postoperative small bowel obstruction occurred in 19 of 197 cases of posterior mediastinal route reconstruction (9.6%), but in no cases of retrosternal route reconstruction because of the feeding gastrostomy (P < .0001). Of the 19 patients who had bowel obstruction after feeding jejunostomy, 10 patients underwent reoperation (53%) and the remaining 9 patients had conservative treatment (47%). The cumulative incidence of bowel obstruction after feeding jejunostomy was 6.7% at 1 year and 8.7% at 2 years. Feeding jejunostomy following esophagectomy is a risk factor for small bowel obstruction. We recommend feeding gastrostomy inserted from the antrum to the jejunum in the cases of gastric tube reconstruction through the retrosternal route or nasogastric feeding tube in the cases of reconstruction through the posterior mediastinal route.     

Ethanol Stimulates Immunoreactive Endothelin-1 and -2 Release from Cultured Human Umbilical Vein Endothelial Cells

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.     

Takayasu arteritis developing during treatment of ulcerative colitis with infliximab

A 22-year-old female with ulcerative colitis that was successfully treated with infliximab (IFX), and remained stable following tapered discontinuation of prednisolone, developed anterior neck pain and elevation of C-reactive protein following her fourth administration of IFX. She was diagnosed with Takayasu arteritis (TA) based on neck ultrasound and computed tomography angiography. This is the first report describing the development of TA during treatment of UC with IFX.     

Unmanipulated Reduced-Intensity Stem Cell Transplantation from a Haploidentical Donor Mismatched at 3 HLA Antigens to a Patient with Leukemic Transformation of Myelodysplastic Syndrome: Successful Second Transplantation after Graft Rejection

We present the case of a patient with myelodysplastic syndrome who experienced leukemia transformation and subsequently underwent transplantation of unmanipulated peripheral blood stem cells from a haploidentical sibling mismatched at 3 HLA antigens, along with a reduced-intensity regimen (fludarabine, busulfan, and anti-T-lymphocyte globulin) and tacrolimus-containing graft-versus-host disease (GVHD) prophylaxis. The patient experienced graft rejection but successfully underwent a second transplantation from the same donor with a slightly intensified conditioning regimen. Although the patient developed life-threatening cytomegalovirus (CMV) pneumonia following the second transplantation, he recovered completely from the pneumonia with intensive supportive therapy. He is still in complete remission past day 1000 in the absence of GVHD. As far as we know, this report is the first to describe a successful second transplantation that was performed for graft rejection following HLA-haploidentical nonmyeloablative stem cell transplantation. Furthermore, we emphasize that patients should be carefully monitored for CMV infection when reduced-intensity conditioning is given repeatedly over a short period.