Development of a cancer cells self­activating and miR­125a­5p expressing poly­pharmacological nanodrug for cancer treatment.

Cancer cells can acquire resistance to targeted therapeutic agents when the designated targets or their downstream signaling molecules develop protein conformational or activity changes. There is an increasing interest in developing poly­pharmacologic anticancer agents to target multiple oncoproteins or signaling pathways in cancer cells. The microRNA 125a­5p (miR­125a­5p) is a tumor suppressor, and its expression has frequently been downregulated in tumors. By contrast, the anti­apoptotic molecule BIRC5/SURVIVIN is highly expressed in tumors but not in the differentiated normal tissues. In the present study, the development of a BIRC5 gene promoter­driven, miR­125a­5p expressing, poly­L­lysine­conjugated magnetite iron poly­pharmacologic nanodrug (pL­MNP­pSur­125a) was reported. The cancer cells self­activating property and the anticancer effects of this nanodrug were examined in both the multidrug efflux protein ABCB1/MDR1­expressing/­non­expressing cancer cells in vitro and in vivo. It was demonstrated that pL­MNP­pSur­125a decreased the expression of ERBB2/HER2, HDAC5, BIRC5, and SP1, which are hot therapeutic targets for cancer in vitro. Notably, pL­MNP­pSur­125a also downregulated the expression of TDO2 in the human KB cervical carcinoma cells. PL­MNP­pSur­125a decreased the viability of various BIRC5­expressing cancer cells, regardless of the tissue origin or the expression of ABCB1, but not of the human BIRC5­non­expressing HMEC­1 endothelial cells. In vivo, pL­MNP­pSur­125a exhibited potent antitumor growth effects, but without inducing liver toxicity, in various zebrafish human­ABCB1­expressing and ABCB1­non­expressing tumor xenograft models. In conclusion, pL­MNP­pSur­125a is an easy­to­prepare and a promising poly­pharmacological anticancer nanodrug that has the potential to manage numerous malignancies, particularly for patients with BIRC5/ABCB1­related drug resistance after prolonged chemotherapeutic treatments.

The "Dark Side" of autophagy on the maintenance of genome stability: Does it really exist during excessive activation?

Dysregulation of DNA damage response/repair and genomic instability promote tumorigenesis and the development of various neurological diseases. Autophagy is a dynamic catabolic process used for removing unnecessary or dysfunctional proteins and organelles in cells. Despite the consensus in the field that upregulation of autophagy promotes the initiation of the DNA damage response and assists the process of homologous recombination upon genotoxic stress, a few studies showed that upregulation of autophagy (or excessive autophagy), under certain circumstances, triggers caspase/apoptosis-independent DNA damage and promotes genomic instability in cells. As the cytoprotective and the DNA repairing roles of autophagy have been discussed extensively in different reviews, here, we mainly focus on describing the latest studies which reported the "opposite" roles of autophagy (or excessive autophagy). We will discuss whether the "dark side" (i.e., the opposite/unconventional effect) of autophagy on the maintenance of DNA integrity and genomic stability really does exist in cells and if it does, will it be one of the yet-to-be-identified causes of cancer, in this review.

Appendiceal hemorrhage -- an uncommon cause of lower gastrointestinal bleeding.

Lower gastrointestinal bleeding is a common disease among elderly patients. The common sources of lower gastrointestinal bleeding include vascular disease, Crohn's disease, neoplasms, inflammatory bowel disease, hemorrhoids, and ischemic colitis. Lower gastrointestinal bleeding arising from the appendix is an extremely rare condition. We report a case of appendiceal hemorrhage in a young male. Diagnosis was made by multidetector computerized tomography during survey for hematochezia. The patient recovered well after appendectomy. The histological finding revealed focal erosion of appendix mucosa with bleeding.

Laparoscopic retrieval of retained intraperitoneal drains in the immediate postoperative period.

Retained intraperitoneal Penrose drain secondary to fracture and adhesions in the immediate postoperative period happens on occasion. Most are unreported because of the fear of medico-legal problems. Previous management of such iatrogenic complications requires repeated laparotomy or wound exploration. Two patients who underwent appendectomy for ruptured appendicitis, with retained intraabdominal drains in the immediate postoperative period, managed eventually by laparoscopic retrieval are presented. Both patients had right low transverse incisions and intraabdominal drains exiting through a separate right lateral abdomen skin opening. Patient 1 had a stuck intraabdominal drain unable to be removed up to the second week. Patient 2's drain retracted intraperitoneally after its mobilization on the sixth post-op day. Both were managed by laparoscopy under general anesthesia with successful removal of both drains. Patient 1 underwent the procedure 3 weeks after the appendectomy, whereas Patient 2 had the procedure on her sixth post-op day. An additional new 1-cm wound in the periumbilical area was done for the introduction of pneumoperitoneum and 10-mm port for which the laparoscope was inserted. The second 5-mm port was inserted through the old drain site wound with peritoneal entry opening separate from the previous peritoneal defect viewed from laparoscope. Both drains had some marked adhesions from ingrowth of omentum to the side holes of the drain, causing it to get stuck in the pelvic cavity. This laparoscopic approach in the management of such iatrogenic complication, besides being cosmetically acceptable, contributes to early recovery and discharge of the patient, and helps to lessen the friction in the recently worsening doctor-patient relationship in Taiwan.