Mucin Hypersecreting Intraductal Papillary Neoplasm of the pancreas.
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Mucin Hypersecreting Intraductal Papillary Neoplasm is a rare neoplasm that arises from ductal epithelial cells. This entity is distinct from the more commonly known Mucinous Cystadenoma or Mucinous Cystadenocarcinoma. Despite this distinction, it has been erroneously categorized with these more common cystic neoplasms. Characteristic clinical presentation, radiographic, and endoscopic findings help distinguish this neoplasm from the cystadenomas and cystadenocarcinomas. Histopathologic identification is not crucial to the preoperative diagnosis. This neoplasm is considered to represent a premalignant condition and, therefore, surgical resection is warranted. Prognosis, following resection, is felt to be curative for the majority of patients. We present two cases of Mucin Hypersecreting Intraductal Papillary Neoplasm and discuss their diagnosis and surgical therapy. (+info)
Cystadenomas and cystadenocarcinomas of the pancreas: a multiinstitutional retrospective study of 398 cases. French Surgical Association.
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OBJECTIVE: To review the features of patients with benign and malignant cystadenomas of the pancreas, focusing on preoperative diagnostic accuracy and long-term outcome, especially for nonoperated serous cystadenomas and resected cystadenocarcinomas. SUMMARY BACKGROUND DATA: Serous cystadenomas (SCAs) are benign tumors. Mucinous cystic neoplasms should be resected because of the risk of malignant progression. A correct preoperative diagnosis of tumor type is based on morphologic criteria. Despite the high quality of recent imaging procedures, the diagnosis frequently remains uncertain. Invasive investigations such as endosonography and diagnostic aspiration of cystic fluid may be helpful, but their assessment is limited to small series. The management of typical SCA may require resection or observation. Survival after pancreatic resection seems better for cystadenocarcinomas (MCACs) than for ductal adenocarcinomas of the pancreas. METHODS: Three hundred ninety-eight cases of cystadenomas of the pancreas were collected between 1984 and 1996 in 73 institutions of the French Surgical Association. Clinical presentation, radiologic evaluation, and surgical procedures were analyzed for 144 operated SCAs, 150 mucinous cystadenomas (MCAs), and 78 MCACs. The outcome of 372 operated patients and 26 nonoperated patients with SCA was analyzed. RESULTS: Cystadenomas represented 76% of all primary pancreatic cystic tumors (398/522). An asymptomatic tumor was discovered in 32% of patients with SCA, 26% of those with MCA, and 13% of those with MCAC. The tumor was located in the head or uncinate process of the pancreas in 38% of those with SCA, 27% of those with MCA, and 49% of those with MCAC. A communication between the cyst and pancreatic duct was discovered in 0.6% of those with SCA, 6% of those with MCA, and 10% of those with MCAC. The main investigations were ultrasonography and computed tomography (94% for SCA, MCA, and MCAC), endosonography (34%, 28%, and 22% for SCA, MCA, and MCAC respectively), endoscopic retrograde cholangiopancreatography (16%, 14%, 22%), and cyst fluid analysis (22%, 31%, 35%). An accurate preoperative diagnosis of tumor type was proposed for 20% of those with SCA (144 cases), 30% of those with MCA, and 29% of those with MCAC. An atypical unilocular macrocyst was observed in 10% of SCA cases. The most common misdiagnosis for mucinous cystic tumors was pseudocyst (9% of MCAs, 15% of MCACs). Intraoperative frozen sections (126 cases) allowed a diagnosis according to definitive histologic examination in 50% of those with SCA and MCA and 62% of those with MCAC. For management, 93% of patients underwent surgery. Nonoperated patients (7%) had exclusively typical SCA. A complete cyst excision was performed in 94% of benign cystadenomas, with an operative mortality rate of 2% for SCA and 1.4% for MCA. Resection was possible in 74% of cases of MCAC. Mean follow-up of 26 patients with nonresected SCAs was 38 months, and no patients required surgery. For resected MCACs, the actuarial 5-year survival rate was 63%. CONCLUSIONS: Spiral computed tomography is the examination of choice for a correct prediction of tumor type. Endosonography may be useful to detect the morphologic criteria of small tumors. Diagnostic aspiration of the cyst allows differentiation of the macrocystic form of SCA (10% of cases) and the unilocular type of mucinous cystic neoplasm from a pseudocyst. Surgical resection should be performed for symptomatic SCAs, all mucinous cystic neoplasms, and cystic tumors that are not clearly defined. Conservative management is wholly justified for a well-documented SCA with no symptoms. An extensive resection is warranted for MCAC because the 5-year survival rate may exceed 60%. (+info)
Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS.
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Six human ovarian cancer cell lines and samples of ascites cells isolated from 27 patients with stage III or IV ovarian papillary serous cystadenocarcinoma were studied individually to test whether recombinant human Mullerian inhibiting substance (rhMIS) acts via its receptor. To do these experiments, we scaled up production of rhMIS and labeled it successfully with biotin for binding studies, cloned the human MIS type II receptor for mRNA detection, and raised antibodies to an extracellular domain peptide for protein detection. These probes were first tested on the human ovarian cancer cell lines and then applied to primary ovarian ascites cells. rhMIS inhibited colony growth of five of six cell lines that expressed the human MIS type II receptor mRNA by Northern analysis while not inhibiting receptor-negative COS cells. Flow cytometry performed on MIS-sensitive ovarian cancer cell lines demonstrated specific and saturable binding of rhMIS (Kd = 10.2 nM). Ascites cells from 15 of 27 or 56% of patients tested bound biotinylated MIS (MIS-biotin) and, of the 11 that grew in soft agarose, 9 of 11 or 82% showed statistically significant inhibition of colony formation. Of the 15 patients who bound biotinylated MIS, mRNA was available for analysis from 9, and 8 of 9 expressed MIS type II receptor mRNA by reverse transcription-PCR, showing a statistically significant correlation, compared with binding, by chi2 analysis (P = 0.025). Solid ovarian cancers were positive for the MIS type II receptor protein by immunohistochemical staining, which colocalized with staining for antibody to CA-125 (OC-125). Thus, the detection of the MIS type I receptor by flow cytometry may be a useful predictor of therapeutic response to MIS and may be a modality to rapidly choose patients with late-stage ovarian cancer for treatment with MIS. (+info)
Mucobilia in association with a biliary cystadenocarcinoma of the caudate duct: a rare cause of malignant biliary obstruction.
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Mucobilia is a rare condition characterized by the accumulation of abundant mucus within the intra- or extrahepatic biliary tree. A variety of hepatobiliary and pancreatic neoplasms are mucin producing and have been associated with the development of mucobilia including biliary mucinosis, biliary papillomatosis, mucin-producing cholangiocarcinoma (MPCC), or cystic neoplasms of the pancreas or biliary tree (cystadenoma or cystadenocarcinoma). We report the case of 46 year-old male with a biliary cystadenocarcinoma of the caudate lobe which resulted in chronic biliary obstruction and relapsing cholangitis. A review of the literature for both mucobilia and biliary cystadenocarcinoma is provided along with a discussion addressing the clinical presentation, diagnosis, treatment, and prognosis for this rare entity. (+info)
Fluorescent neoglycolipids. Improved probes for oligosaccharide ligand discovery.
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A second generation of lipid-linked oligosaccharide probes, fluorescent neoglycolipids, has been designed and synthesized for ligand discovery within highly complex mixtures of oligosaccharides. The aminolipid 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine (DHPE), which has been used extensively to generate neoglycolipids for biological and structural studies, has been modified to incorporate a fluorescent label, anthracene. This new lipid reagent, N-aminoacetyl-N-(9-anthracenylmethyl)-1, 2-dihexadecyl-sn-glycero-3-phosphoethanolamine (ADHP), synthesized from anthracenaldehyde and DHPE gives an intense fluorescence under UV light. Fluorescent neoglycolipids derived from a variety of neutral and acidic oligosaccharides by conjugation to ADHP, by reductive amination, can be detected and quantified by spectrophotometry and scanning densitometry, and resolved by TLC and HPLC with subpicomole detection. Antigenicities of the ADHP-neoglycolipids are well retained, and picomole levels can be detected using monoclonal carbohydrate sequence-specific antibodies. Among O-glycans from an ovarian cystadenoma mucin, isomeric oligosaccharide sequences, sialyl-Lea- and sialyl-Lex-active, could be resolved by HPLC as fluorescent neoglycolipids, and sequenced by liquid secondary-ion mass spectrometry. Thus the neoglycolipid technology now uniquely combines high sensitivity of immuno-detection with a comparable sensitivity of chemical detection. Principles are thus established for a streamlined technology whereby an oligosaccharide population is carried through ligand detection and ligand isolation steps, and sequence determination by mass spectrometry, enzymatic sequencing and other state-of-the-art technologies for carbohydrate analysis. (+info)
Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 and NF-kappaB.
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The present study was designed to investigate the growth regulatory effects of cytokines in UT-OC-3 ovarian cystadenocarcinoma cells in vitro. The effects of interleukin-6 (IL-6), interferons alpha (IFN-alpha) and gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor alpha (TNF-alpha), and transforming growth factor beta1 (TGF-beta1) were investigated by (125)I-deoxyuridine ((125)IUdR) incorporation assay. In order to understand better the molecular mechanisms of the observed effects, the activation of DNA-binding proteins was studied by electrophoretic mobility shift assay. In addition, cellular DNA was tested by fragmentation analysis to determine if the most growth inhibitory cytokines are able to induce programmed cell death (apoptosis). After 48h in culture, TGF-beta1, TNF-alpha, IFN-alpha and IL-6 showed a clear inhibitory effect on (125)IUdR incorporation (P<0.005), and IFN-gamma and GM-CSF caused even more significant inhibition (P<0.001). IFN-alpha and IFN-gamma were both growth inhibitory after 72h in culture (P<0.005). Similarly, GM-CSF induced a slight inhibition (P<0.05), whereas TGF-beta1 and TNF-alpha almost blocked DNA synthesis (P<0.001) after 72h. IL-6 had no statistically significant effect on cell proliferation after 72h. Transcription factors AP-1 and NF-kappaB were both constitutively expressed in UT-OC-3 cells. The binding activity of AP-1 was found to be stimulated by the growth inhibitory cytokines, TGF-beta1 and TNF-alpha, and the binding of NF-kappaB was stimulated by TNF-alpha. Apoptosis does not seem to be induced by any of these cytokines in the UT-OC-3 ovarian cancer cell model. (+info)
Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs.
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Canine hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a rare, naturally occurring inherited cancer syndrome observed in dogs. Genetic linkage analysis of an RCND-informative pedigree has identified a linkage group flanking RCND (CHP14-C05.377-C05.414-FH2383-C05. 771-[RCND-CPH18]-C02608-GLUT4-TP53-ZuBe Ca6-AHT141-FH2140-FH2594) thus localizing the disease to a small region of canine chromosome 5. The closest marker, C02608, is linked to RCND with a recombination fraction (theta) of 0.016, supported by a logarithm of odds score of 16.7. C02608 and the adjacent linked markers map to a region of the canine genome corresponding to portions of human chromosomes 1p and 17p. A combination of linkage analysis and direct sequencing eliminate several likely candidate genes, including tuberous sclerosis 1 and 2 genes (TSC1 and TSC2) and the tumor suppressor gene TP53. These data suggest that RCND may be caused by a previously unidentified tumor suppressor gene and highlight the potential for canine genetics in the study of human disease predisposition. (+info)
Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer.
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We previously demonstrated that AKT2, a member of protein kinase B family, is activated by a number of growth factors via Ras and PI 3-kinase signaling pathways. Here, we report the frequent activation of AKT2 in human primary ovarian cancer and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase (PI 3-kinase)/Akt pathway. In vitro AKT2 kinase assay analyses in 91 ovarian cancer specimens revealed elevated levels of AKT2 activity (>3-fold) in 33 cases (36.3%). The majority of tumors displaying activated AKT2 were high grade and stages III and IV. Immunostaining and Western blot analyses using a phospho-ser-473 Akt antibody that detects the activated form of AKT2 (AKT2 phosphorylated at serine-474) confirmed the frequent activation of AKT2 in ovarian cancer specimens. Phosphorylated AKT2 in tumor specimens localized to the cell membrane and cytoplasm but not the nucleus. To address the mechanism of AKT2 activation, we measured in vitro PI 3-kinase activity in 43 ovarian cancer specimens, including the 33 cases displaying elevated AKT2 activation. High levels of PI 3-kinase activity were observed in 20 cases, 15 of which also exhibited AKT2 activation. The remaining five cases displayed elevated AKT1 activation. Among the cases with elevated AKT2, but not PI 3-kinase activity (18 cases), three showed down-regulation of PTEN protein expression. Inhibition of PI 3-kinase/AKT2 by wortmannin or LY294002 induces apoptosis in ovarian cancer cells exhibiting activation of the PI 3-kinase/AKT2 pathway. These findings demonstrate for the first time that activation of AKT2 is a common occurrence in human ovarian cancer and that PI 3-kinase/Akt pathway may be an important target for ovarian cancer intervention. (+info)