The pancreatic cancer is the fourth leading cause of cancer-related death and characterized by one of the lowest five-year survival rate. The current therapeutic options are demonstrating minimal effectiveness, therefore studies on new potential anticancer compounds, with non-significant side effects are highly desirable. Recently, it was demonstrated that vanadium compounds, in particular organic derivatives, exhibit anticancer properties against different type of tumor as well as favorable biodistribution from a pancreatic cancer treatment perspective.In this research, we showed selective cytotoxic effect of vanadium complexes, containing phenanthroline and quinoline as an organic ligands, against human pancreatic ductal adenocarcinoma cell line (PANC-1), compared to non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE). Results exhibited that vanadium complexes inhibited autophagy process in selective cytotoxic concentration as well as caused the cell cycle arrest in G2/M phase associated with mitotic catastrophe and increased level of reactive oxygen species (ROS). Moreover, in higher concentration, vanadium derivatives induced a mix type of cell death in PANC-1 cells, including apoptotic and necroptotic process.Our investigation emphasizes the anticancer potential of vanadium complexes by indicating their selective cytotoxic activity, through different process posed by alternative type of cell deaths to apoptosis-resistant cancer cells. Further studies supporting the therapeutic potential of vanadium in pancreatic cancer treatment is highly recommended.
The effect of aging on metabolic enzyme activity remains controversial, possibly due to physical activity differences. We examined the effect of aging on the enzyme activity for anaerobic and aerobic pathways in nonweight-bearing human skeletal muscle from relatively sedentary males. The muscle obliquus internus abdominis was analyzed for anaerobic (creatine kinase, adenylate kinase, and lactate dehydrogenase) and aerobic (2-oxoglutarate dehydrogenase and carnitine palmitoyltransferase) enzyme activities in two groups: middle-aged (29-54 years) and older (61-74 years) adults. All enzyme activities were lower in older versus middle-aged adults when results were expressed as muscle wet weight (p <.05). When activity was expressed relative to the protein content, only lactate dehydrogenase remained significantly lower in older versus middle-aged adults (p <.001). In conclusion, some of the reduction in muscle performance in older adults may be due to lower activity of the anaerobic and aerobic enzymes as well as protein content, not solely due to a decrease in physical activity.
Ligation of the inferior mesenteric artery (IMA) during sigmoid colectomy may cause sympathetic denervation of the rectal stump. The purpose of our study was to investigate the functional results after sigmoid resection following ligation or preservation of the IMA. We prospectively analysed 44 patients (21 female and 23 male, mean age 60.6 +/- 11.79 years) with sigmoid tumour. Sigmoid colectomy with preservation of the IMA was performed in 21 patients, and ligation of the IMA with sigmoidectomy was carried out in 23 patients. Bowel function follow-up was performed by use of questionnaires: standardized functional questionnaire, constipation-specific, and incontinence scales before, 6 and 12 months after surgery. The quality of life was measured by means of the Fecal Incontinence Quality of Life (FIQL) scale. After sigmoid colectomy with division of the IMA, patients presented with a higher rate of fecal incontinence and increased stool frequency compared with patients after sigmoid resection with preservation of the IMA. Deterioration of FIQL was also observed in patients with ligated IMA. Preservation of the IMA during sigmoid colectomy in selected patients lowers the frequency of postoperative impaired anorectal function.
The more favourable patient profile provided justification for a laparoscopic procedure. For those converted to an open procedure, however, there were significantly more complications than planned open surgery patients. A move away from the standard open procedure for rectal cancer surgery and towards laparoscopy is not yet feasible.
Pancreatic cancer is characterized by one of the lowest five-year survival rates. In search for new treatments, some studies explored several metal complexes as potential anticancer drugs. Therefore, we investigated three newly synthesized oxidovanadium(IV) complexes with 2-methylnitrilotriacetate (bcma3−), N-(2-carbamoylethyl)iminodiacetate (ceida3−) and N-(phosphonomethyl)-iminodiacetate (pmida4−) ligands as potential anticancer compounds using pancreatic cancer cell lines. We measured: Cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) assay; antiproliferative activity by bromodeoxyuridine BrdU assay; reactive oxygen species (ROS) generation and cell cycle analysis by flow cytometry; protein level by Western blot and cellular morphology by confocal laser scanning microscopy. The results showed that these oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2), but not on non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE) over the concentration range of 10–25 μM, following 48 h incubation. Furthermore, molecular mechanisms of cytotoxicity of [4-NH2-2-Me(Q)H][VO(bcma)(H2O)]2H2O (T1) were dependent on antiproliterative activity, increased ROS generation, cell cycle arrest in G2/M phase with simultaneous triggering of the p53/p21 pathway, binucleation, and induction of autophagy. Our study indicates that oxidovanadium(IV) coordination complexes containing 2-methylnitrilotriacetate ligand are good candidates for preclinical development of novel anticancer drugs targeting pancreatic cancer.
Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.
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