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Transarterial chemoembolization (TACE) is considered a standard local-regional treatment for intermediate-stage hepatocellular carcinoma (HCC) and the most common bridging therapy. This treatment is offered to more than 70% of patients who are on the waiting list for liver transplantation in the United States. HCC typically receives its blood supply from the hepatic artery; however, it can recruit a parasitic supply from extrahepatic collateral (EHC) arteries. The development of an EHC arterial blood supply can interfere with the therapeutic efficacy of TACE and result in treatment failure and poor outcome. Cross-sectional imaging-specifically computed tomography and magnetic resonance imaging-has some limitations in depicting the presence or absence of an EHC arterial supply during the pre-TACE evaluation. Catheterization and angiography of every possible EHC artery during a routine TACE procedure would be time consuming and technically challenging and would not always be feasible. Therefore, the prediction of a potential EHC arterial supply on the basis of tumor location before, during, and after TACE is fundamental to achieving optimal therapeutic efficacy. To perform TACE through EHC arteries, special considerations are necessary to avoid potentially serious complications. The authors review the factors influencing the development of an EHC arterial blood supply to HCC and describe a systematic approach to enhance the ability to predict the presence of EHC arteries. They also describe the proper technique for TACE of each EHC artery and how to avoid potential technique-related complications. RSNA, 2017.

Using differential cDNA library screening techniques based on metastatic and nonmetastatic rat mammary adenocarcinoma cell lines, we previously cloned and sequenced the metastasis-associated gene mta1. Using homology to the rat mta1 gene, we cloned the human MTA1 gene and found it to be over-expressed in a variety of human cell lines (breast, ovarian, lung, gastric and colorectal cancer but not melanoma or sarcoma) and cancerous tissues (breast, esophageal, colorectal, gastric and pancreatic cancer). We found a close similarity between the human MTA1 and rat mta1 genes (88% and 96% identities of the nucleotide and predicted amino acid sequences, respectively). Both genes encode novel proteins that contain a proline rich region (SH3-binding motif), a putative zinc finger motif, a leucine zipper motif and 5 copies of the SPXX motif found in gene regulatory proteins. Using Southern blot analysis the MTA1 gene was highly conserved, and using Northern blot analysis MTA1 transcripts were found in virtually all human cell lines (melanoma, breast, cervix and ovarian carcinoma cells and normal breast epithelial cells). However, the expression level of the MTA1 gene in normal breast epithelial cells was approximately 50% of that found in rapidly growing adenocarcinoma and atypical epithelial cell lines. Experimental inhibition of MTA1 protein expression using antisense phosphorothioate oligonucleotides resulted in inhibition of growth and invasion of human MDA-MB-231 breast cancer cells with relatively high MTA1 expression. Furthermore, the MTA1 protein was localized in the nuclei of cells transfected with a mammalian expression vector containing a full-length MTA1 gene. Although some MTA1 protein was found in the cytoplasm, the vast majority of MTA1 protein was localized in the nucleus. Examination of recombinate MTA1 and related MTA2 proteins suggests that MTA1 protein is a histone deacetylase. It also appears to behave like a GATA-element transcription factor, since transfection of a GATA-element reporter into MTA1-expressing cells resulted in 10-20-fold increase in reporter expression over poorly MTA1-expressing cells. Since it was reported that nucleosome remodeling histone deacetylase complex (NuRD complex) involved in chromatin remodeling contains MTA1 protein and a MTA1-related protein (MTA2), we examined NuRD complexes for the presence of MTA1 protein and found an association of this protein with histone deacetylase. The results suggest that the MTA1 protein may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of metastatic epithelial cells.

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Background:The efficacy of an extract from date seeds has been tested successfully on the glycemic control of type I diabetes mellitus in rats. A suggestion that date seed extract could stimulate certain cells to differentiate into insulin-secreting cells has been proposed. In order to investigate such a possibility, this study was conducted to measure C-peptide levels in the serum of type 1 diabetic rats treated with date seed extract. Methods:Two hundred rats were divided into 4 groups. Group I served as the control. Group II was given daily ingestions of 10 ml of date seed extract. Groups III and IV were made diabetic by streptozotocin injection and were given daily subcutaneous injections of 3 IU/day of insulin for 8 weeks. Group IV received, in addition, daily ingestions of 10 ml of seed extract. At the end of experiment, blood samples were collected from each rat, and blood glucose and serum Cpeptide levels were measured.Results: No significant differences in the means of blood glucose and serum C-peptide levels were observed between groups I (control group) and II (date seed extract-treated control group). Group IV (date seed extract-insulin-treated diabetic group) showed a statistically significant reduction in the mean blood glucose level compared to Group III (insulin-treated diabetic group). The mean serum C-peptide level was significantly higher in group IV compared to group III. Conclusion:Biochemical results suggested an increase in endogenous insulin secretion in the case of type 1 diabetic rats treated with date seed extract, which might be the cause of its hypoglycemic effect. BACKGROUND:Diabetes is a predominant public health concern affecting a large population in the whole world. The disease causes substantial morbidity, mortality, and long-term complications [1,2]. Insulin is the only drug currently available to treat type 1 diabetes mellitus (T1DM), and its disadvantages have been discussed in previous studies [3,4]. There is an increasing use of complementary and alternative medicine among general public [5]. In a previous study, we successfully tested the efficacy of an aqueous extract from date seeds on the glycemic control of T1DM in rats [6].In another study, we demonstrated the safety of date seed extract administration on liver and kidneys of rats, and showed that a date seed extract-insulin combination minimizes the diabetic toxic effects on the liver and kidneys of rats, compared to insulin administration as a single drug [7]. However, the potential mechanism by which date seed extract exerts its hypoglycemic effect remains uninvestigated. A suggestion that such an extract could stimulate certain cells to differentiate into insulin-secreting cells has been proposed [6].C-peptide (connecting peptide), a 31-amino-acid polypeptide, represents the midportion of the proinsulin molecule. During insulin secretion, it is enzymatically cleaved off and cosecreted in equimolar proportion with mature insulin molecules. Because synthetic insulin does not have such a peptide, the level...

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet (n = 5) and one undergoing bariatric surgery (n = 7), used both targeted and untargeted proteomic approaches to determine changes in protein levels pre- and post-intervention (i.e. 3-6 months later). Changes were observed in both circulating and excreted proteins following weight loss. Targeted multiplexed biochip arrays measured 12 plasma peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin, interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C-reactive protein. Following a low-calorie diet, plasma insulin and C-reactive protein levels were significantly reduced (P = 0.045 and P = 0.030, respectively); adiponectin increased and leptin decreased following surgery (P = 0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D difference in-gel electrophoresis (DIGE) showed 28 protein spots with ≥1.5-fold changes in expression following weight loss by a low-calorie diet; comparison of pre- and post-intervention urine samples from the bariatric surgery group showed changes in excretion of 110 protein spots. The combination of targeted protein analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery) proteomic assessment of hundreds of proteins offers valuable insights into the mechanistic differences between alternative weight-loss strategies. This is a powerful hypothesis-generating approach to study complex, multifactorial syndromes such as obesity. The findings that arise from these studies can then be validated in targeted, hypothesis-directed investigations.

The aim of this study is to compare the outcomes of the elective-start versus urgent-start use of peritoneal dialysis (PD) catheters using percutaneous radiologic or laparoscopic techniques. Patients having their first peritoneal dialysis catheter placed and used between January 2005 and January 2018 were identified, and their medical records were retrospectively reviewed. Two groups were identified: elective-start (n = 211) and urgent-start (n = 29). Patient’s demographics were similar between the two groups with the exception of age, which was higher in the elective-start group. The catheter complication rates and catheter removal rates at 3 and 12 months, mean days-to-first complication, mean days-to-catheter removal, and overall patient survival at 12 months were analyzed. Catheter complication rates at 3 and 12 months were similar between the two groups (27.8% and 48.9%, respectively, in the elective-start group versus 35.9% and 54.2%, respectively, in the urgent-start group, p=0.415). The catheter removal rates at 3 and 12 months were also similar between the two groups (p=0.088). Catheter leak was higher in the urgent-start group (13.8% versus 3.3%, respectively, p=0.011). There was no difference between the elective-start and the urgent-start groups in the mean days-to-first complication (95 vs 69, p=0.086), mean days-to-catheter removal (145 vs 127, p=0.757), and overall patient survival at 12 months (100% vs 97%, p=0.41). In conclusion, apart from catheter leak, there were similar rates of catheter complication and removal for PD catheter used for the elective-start compared to the urgent-start PD. Furthermore, the technique of placement did not affect the outcomes.