We have recently cloned the mouse activity-dependent neuroprotective protein (ADNP). Here, we disclose the cloning of human ADNP (hADNP) from a fetal brain cDNA library. Comparative sequence analysis of these two ADNP orthologs indicated 90% identity at the mRNA level. Several single nucleotide polymorphic sites were noticed. The deduced protein structure contained nine zinc fingers, a proline-rich region, a nuclear bipartite localization signal, and a homeobox domain profile, suggesting a transcription factor function. Further comparative analysis identified an ADNP paralog (33% identity and 46% similarity), indicating that these genes belong to a novel protein family with a nine-zinc finger motif followed by a homeobox domain. The hADNP gene structure spans ϳ40 kilobases and includes five exons and four introns with alternative splicing of an untranslated second exon. The hADNP gene was mapped to chromosome 20q12-13.2, a region associated with aggressive tumor growth, frequently amplified in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers. hADNP mRNA is abundantly expressed in distinct normal tissues, and high expression levels were encountered in malignant cells. Down-regulation of ADNP by antisense oligodeoxynucleotides up-regulated the tumor suppressor p53 and reduced the viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in maintaining cell survival, perhaps through modulation of p53.Mouse activity-dependent neuroprotective protein (mADNP), 1 a novel vasoactive intestinal peptide (VIP)-responsive gene, was recently cloned (1). The relative enrichment of mADNP transcripts in the cerebellum, cortex, hippocampus, medulla, and midbrain and the increases found in the presence of VIP, an established neuroprotective substance (2), implied a potential function in brain metabolism. Specifically, mADNP mRNA increased 2-3-fold in astroglial cells incubated for 3 h in the presence of nanomolar amounts of VIP (1). Another tissue containing increased mADNP transcripts is the mouse testis, a highly proliferative tissue, suggesting the involvement of ADNP in cell division.As deregulation of oncogenes has been associated with neurodegeneration (3), pathways that regulate neuronal survival may impinge upon cancer proliferation. VIP regulates both neuronal survival and cell division (2). A system whereby labeled VIP is suggested as a tumor marker has been proposed, localizing in vivo tumors of patients with gastrointestinal neuroendocrine cancers as well as pancreatic and colonic adenocarcinomas (4). Other studies have identified a very high incidence of VIP receptor binding in breast, ovarian, endometrial, prostate, bladder, lung, esophageal, colonic, and pancreatic tumors as well as in neuroendocrine and brain tumors (5). However, the VIP effect on cancer growth depends on the specific tumor and may be stimulatory (6, 7) or inhibitory (8). In view of the high incidence of tumors containing VIP receptors, a potential intervention in tumor growth may employ a gene downstr...
The effects of vasoactive intestinal peptide (VIP) antagonists on breast cancer cells were investigated. (N-stearyl, norleucine17)VIP hybrid ((SN)VIPhyb) inhibited specific 125I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and MDA-MB231 cells with high affinity (IC50 values of 0.03-0.06 microM). (SN)VIPhyb, 1 microM, inhibited the ability of 10 nM VIP to cause elevation of cAMP and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibited the proliferation of MDA-MB231 or MCF7 cells using a MTT and clonogenic assay. Using a MTT assay, (SN)VIPhyb enhanced the ability of taxol and doxorubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231 xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferation. The results indicate that VIP receptor antagonists increase the ability of chemotherapeutic drugs to kill breast cancer cells.
BACKGROUND Vasoactive intestinal peptide (VIP) is one of several small neuropeptides that affect cancer growth. A lipophilic VIP analog, stearyl‐Nle17‐neuroten‐ sin6‐11VIP7‐28 (SNH) that inhibited lung carcinoma growth has been described previously. The experiments performed were clonogenic assays in vitro and tumor xenografts in nude mice in vivo. These studies were now extended to colon carcinoma and to combination therapy with chemotherapeutic agents. METHODS Assays were performed with cell lines, and tumor proliferation was assessed using the (3‐[4,5‐dimethylthiazol‐2‐yl‐5]‐[3‐carboxymethoxyphenyl]‐2‐[4‐sulfophenyl]‐2H tetrazolium) (MTS) colorimetric assay for mitochondrial function of living cells. RESULTS The lipophilic analog (SNH) enhanced the antiproliferative activity of diverse chemotherapeutic agents: doxorubicine (antibiotic); vinorelbine (vinca alkaloid, antimicrotubule formation); paclitaxel (antimicrotubule agent); gemcitabine (antimetabolite); irinotecan (topoisomerase I inhibitor); and cisplatin (platinum compound acting as an alkylating agent). In all cases, the antiproliferative effect of SNH and the chemotheraputic agent was at least additive and for some combinations and concentrations even synergistic. For example, 2 μM of the antagonist that produced a 15–20% growth inhibition in the nonsmall cell lung carcinoma cell line reduced the IC50 by 2–4‐fold for most of the chemotherapeutic agents tested. Higher analog concentrations were even more efficacious. Similar results were obtained with colon carcinoma cell lines. CONCLUSIONS Chemotherapeutic treatment of advanced solid tumors, such as nonsmall cell lung carcinoma, colon carcinoma, or prostate carcinoma, achieves a response rate of between 10% and 30% with significant toxicity. Combination therapy with the lipophilic VIP analog SNH and the preferred chemotherapeutic agent may greatly enhance the response rate, and by permitting a dose reduction, should significantly reduce side effects. Cancer 2001;92:2172–80. © 2001 American Cancer Society.
Aim Quality of documentation of patient notes Method Guidance for standards was taken from ‘The importance of Clinical Documentation, Ann R Coll Surg Engl(Suppl) 2014; 96:18–20’ Data of 100 patients over 2 weeks. Assessed: Results Availability of notes: 15/100 notes were not available on the wards at the time of data collection Conclusions Based on above results the significances of: Results Unable to provide proof of treatment if any abnormalities were found and medical negligence
Summary. Actinomycosis involving the colon is rare. The aim of the present article is to reportan additional case of this rare entity. A young female has been operated upon for suspected presence of sigmoid neoplasm. A mass involving the sigmoid colon, the apex of the urinary bladder, the fundus of the uterus and the left adnexa was found. En-block resection was performed. Histological examination confirmed the diagnosis of actinomycosis. Most of the cases of colonic actinomycosis were diagnosod postoperatively. Whether more accurate preoperative diagnosis should be possible in the future is still an unanswered question.
Aim Group and save studies prior to appendicectomy Method 219 appendicectomy cases from Jan 2018 until Dec 2020. This was to look for whether patients had a blood transfusion post appendicectomy. Whether this was cost effective? Results 19/219 did not have G and S studies performed. None of the patients required a blood transfusion post operatively. Price per bottle £20 Conclusions Based on the above results we referred to the study performed by the RCS Royal College of Surgeons did a study on ‘blood group and antibody screening prior to emergency laparoscopy’. Study included 562 cases. Concluded that routine G&S studies are not required and ‘majority of patients had a low risk of major intraoperative haemorrhage’ and thus G&S was not warranted O –ve blood can be used in cases of acute haemorrhage from major vessel injury Time taken to receive O neg blood = minutes.
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