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Sample records for giant mucinous adenocarcinoma

  1. Primary appendiceal mucinous adenocarcinoma.

    PubMed

    Behera, Prativa Kumari; Rath, Pramod Kumar; Panda, Rabiratna; Satpathi, Sanghamitra; Behera, Rajan

    2011-04-01

    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  2. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    PubMed

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe

    2009-02-01

    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  3. Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival.

    PubMed

    Geles, Abidin; Gruber-Moesenbacher, Ulrike; Quehenberger, Franz; Manzl, Claudia; Al Effah, Mohamed; Grygar, Elisabeth; Juettner-Smolle, Freyja; Popper, Helmut H

    2015-12-01

    Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.

  4. Clinical outcomes among women with mucinous adenocarcinoma of the ovary

    PubMed Central

    Massad, L. Stewart; Gao, Feng; Hagemann, Ian; Powell, Mathew

    2016-01-01

    Background/Aims Patterns of metastasis and clinical behavior of mucinous ovarian cancers are poorly understood because of their rarity. Methods A retrospective review of records of women identified with pure mucinous invasive ovarian/tubal/peritoneal cancer 1992–2012 at one institution. Survival differences were compared using Kaplan-Meier methods with log-rank tests. Results Among 42 women with mucinous adenocarcinomas the median age was 55 years (range 33–83 years). Most cancers were well differentiated (n = 26, 68%) and stage I/II (n = 31, 74%). One of 27 women with sampled nodes had nodal metastasis; one additional woman recurred in a pelvic node. Most had no visible residual tumor after initial surgery, but of 10 women with stage III/IV cancer and documented residual, 8 had >2cm residual. Except for one woman alive with disease at last follow-up, all who recurred died of disease. Five-year survival was 83% for stage I/II cases but 29% among stage III/IV cases. Stage was a strong predictor of survival (hazard ratio of death among women with stage III/IV cancer 7.73, 95% C.I. 2.33–25.66, P<0.001 vs women with stage I/II cancer). Conclusion Mucinous ovarian cancers have a distinct biology, such that lymphadenectomy for staging is unnecessary and metastatic cancers have poor prognosis. PMID:26583769

  5. Giant Mucinous Cystadenoma in Nnewi, Nigeria

    PubMed Central

    Okafor, CI; Onyegbule, OA; Etigbue, J; Uyoh, IS; Ezenri, U

    2015-01-01

    Mucinous ovarian tumors are the second commonest type of epithelial ovarian tumors. Most of these tumors are benign. Occasionally, these tumors may reach enormous dimensions without being symptomatic. We reported the occurrence of a huge benign ovarian tumor (mucinous cystadenoma) in Nnewi. The data were collected from history taking, clinical examination, laboratory investigation, ultrasonographic examination, operative findings and histopathological examination of the surgical specimen. The case was reported as a massive ovarian mucinous cystadenoma. This case report emphasizes the importance of a thorough evaluation of women who presented with vague abdominal pain. Although the condition is very rare, it is potentially hazardous if early diagnosis and timely intervention is not instituted PMID:26097766

  6. Primary enteric-type mucinous adenocarcinoma of the urethra in a patient with ulcerative colitis.

    PubMed

    Dimitroulis, Dimitrios; Patsouras, Dimitrios; Katsargyris, Athanasios; Charalampoudis, Petros; Anastasiou, Ioannis; Kouraklis, Gregory

    2014-01-01

    Primary carcinoma of the male urethra accounts for less than 1% of malignancies in men. Mucinous adenocarcinoma of the urethra is extremely rare, and its biologic behavior is poorly understood. We present herein a rare case of mucinous urethral adenocarcinoma in a male patient with longstanding ulcerative colitis and multiple sclerosis. The patient presented with a voluminous pelvic mass; core biopsy of the lesion demonstrated a mucus-producing adenocarcinoma. Given the patient's history of subtotal colectomy, preoperative diagnosis was oriented towards a rectal stump adenocarcinoma. The patient underwent a pelvic exenteration: surprisingly, histology marked the prostatic urethra as the primary lesion site.

  7. Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas

    PubMed Central

    Wahrenbrock, Mark; Borsig, Lubor; Le, Dzung; Varki, Nissi; Varki, Ajit

    2003-01-01

    Trousseau described spontaneous, recurrent superficial migratory thrombophlebitis associated with occult cancers, and this was later correlated with disseminated microangiopathy (platelet-rich clots in small blood vessels). Trousseau syndrome often occurs with mucinous adenocarcinomas, which secrete abnormally glycosylated mucins and mucin fragments into the bloodstream. Since carcinoma mucins can have binding sites for selectins, we hypothesized that selectin-mucin interactions might trigger this syndrome. When highly purified, tissue-factor free carcinoma mucin preparations were intravenously injected into mice, platelet-rich microthrombi were rapidly generated. This pathology was markedly diminished in P- or L-selectin–deficient mice. Heparin (an antithrombin-potentiating agent that can also block P- and L-selectin recognition of ligands) ameliorated this platelet aggregation, but had no additional effect in P- or L-selectin–deficient mice. Inhibition of endogenous thrombin by recombinant hirudin also did not block platelet aggregation. Mucins generated platelet aggregation in vitro in hirudinized whole blood, but not in platelet-rich leukocyte-free plasma nor in whole blood from L-selectin–deficient mice. Thus, Trousseau syndrome is likely triggered by interactions of circulating carcinoma mucins with leukocyte L-selectin and platelet P-selectin without requiring accompanying thrombin generation. These data may also explain why heparin ameliorates Trousseau syndrome, while vitamin K antagonists that merely depress thrombin production do not. PMID:12975470

  8. [Mucinous adenocarcinoma of the renal pelvis associated with renal calculi of the inflammatory type].

    PubMed

    Kalafatis, P; Zarifis, I; Sotrillis, T; Stefis, A

    1999-03-01

    A rare case of mucinous adenocarcinoma of the renal pelvis associated with renal staghorn calculosis in a 60-years-old male patient with pyuria and mucin content of the urine is presented. History was significant for recurrent calculosis of the left kidney. A non functioning hydronephrotic left kidney with staghorn calculosis was diagnosed. Laboratory tests were remarkable only for Carcinoembrionic Antigen (CEA). Pathology of the surgical specimen followed by its immunoreactivity revealed an intestinal type metaplasia and papillary, tubular and mucinous adenocarcinoma of the renal pelvis. Pathogenesis of the intestinal metaplasia and the role of chronic irritation of the urothelium are mentioned.

  9. Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity.

    PubMed

    Ebru, Tastekin; Omer, Yalcin; Fulya, Oz Puyan; Ufuk, Usta; Kemal, Kutlu

    2012-10-01

    Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where "adenocarcinoma not otherwise specified" is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings.

  10. Mucin-positive epithelial mesotheliomas: a histochemical, immunohistochemical, and ultrastructural comparison with mucin-producing pulmonary adenocarcinomas.

    PubMed

    Hammar, S P; Bockus, D E; Remington, F L; Rohrbach, K A

    1996-01-01

    Pathologists routinely use histochemistry, immunohistochemistry, and electron microscopy to differentiate epithelial mesotheliomas from pulmonary adenocarcinomas. Epithelial mesotheliomas are usually mucicarmine-, PAS-diastase, and carcinoembryonic antigen-negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine- and PAS-diastase-positive, and about 90% express polyclonal carcinoembryonic antigen. During a pathologic evaluation of pleural neoplasms between 1975 and 1990, 10 epithelial mesotheliomas were identified that were mucicarmine- and in some instances PAS-diastase-positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four mesotheliomas focally expressing carcinoembryonic antigen. The mucicarmine, PAS-diastase, and carcinoembryonic antigen staining were usually eradicated or reduced in intensity by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive mucin reactions. In three cases the epithelial mesotheliomas showed focal regions of mucicarmine, PAS-d-, and Alcian blue-hyaluronidase-resistant staining. In contrast, 10 mucicarmine-, PAS-diastase-, Alcian blue-, and carcinoembryonic antigen-positive pulmonary adenocarcinomas were not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of well- to moderately well-differentiated epithelial mesotheliomas, the mucin-positive epithelial mesotheliomas often showed medium-electron-dense secretory material covering the microvilli, aggregates of medium electron-dense material in association with the microvilli, producing an ultrastructural morphology that has been observed only in epithelial mesotheliomas.

  11. Invasive mucinous adenocarcinoma mimicking organizing pneumonia associated with Mycobacterium fortuitum infection.

    PubMed

    Morichika, Daisuke; Miyahara, Nobuaki; Hotta, Katsuyuki; Okamoto, Yoshiko; Minami, Daisuke; Irie, Masahiro; Tanimoto, Yasushi; Kanehiro, Arihiko; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-01-01

    We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum. The patient's lung consolidation rapidly progressed; however, repeated bronchoscopy showed no atypical cells, thus suggesting a diagnosis of organizing pneumonia associated with M. fortuitum infection. However, the surgical biopsy specimen was diagnostic for adenocarcinoma, with no mycobacterial infection. Invasive mucinous adenocarcinoma should not be excluded in the differential diagnosis of patients with clinical features of organizing pneumonia and nontuberculous mycobacterium infection, even if a transbronchial biopsy confirms the absence of malignancy.

  12. Primary mucinous adenocarcinoma of the female urethra: a contemporary clinicopathologic analysis.

    PubMed

    Harari, Saul E; Cheng, Liang; Osunkoya, Adeboye O

    2016-01-01

    Primary mucinous adenocarcinoma of the female urethra is very rare and may lead to both diagnostic and therapeutic challenges. Although primary mucinous adenocarcinoma of the prostate and prostatic urethra has been well characterized in men, this is the largest clinicopathologic study to date of primary mucinous adenocarcinoma of the female urethra. A search was made through the files of 2 major academic institutions for cases of confirmed primary mucinous adenocarcinoma arising from the female urethra. Tumors arising from adjacent organs were excluded both clinically and pathologically in all cases. Five cases were identified. The mean patient age was 67 years (range, 54-74 years). All patients presented with a polypoid/papillary mass arising from the urethra. Pathologic stages were as follows: pT4 3 (60%) of 5 cases; pT3 1 (20%) of 5 cases, and pT2 1 (20%) of 5 cases. Immunohistochemical stains for GATA3, p63, CK7, CK20, CDX2, ER, PAX8, and β-catenin were performed on all cases. Immunohistochemical stains were positive in the tumor cells for CDX2 in 4/5 (80%) cases; focally positive for CK20 in 4/5 (80%) cases; focally positive for CK7 in 4/5 cases (80%); and negative for p63, GATA3, ER, PAX8 and β-catenin in all cases. In the 4 patients with available follow-up data, mean follow-up was 25 months (range, 4-54 months). It is critical for pathologists to be aware of this entity in light of potential diagnostic pitfalls and therapeutic implications.

  13. Mucinous adenocarcinoma of perianal region: an uncommon disease treated with neo-adjuvant chemo-radiation.

    PubMed

    Purkayastha, Abhishek; Sharma, Neelam; Dutta, Vibha; Bisht, Niharika; Pandya, Tejas

    2016-01-01

    Mucinous adenocarcinoma of the perianal region is an oncologic rarity posing a diagnostic and therapeutic dilemma for treating oncologists due to very few reported cases without definite therapeutic guidelines. It accounts for 2% to 3% of all gastrointestinal malignancies and are historically known to arise from chronic anal fistulas and ischiorectal or perianal abscesses. We hereby report a sporadic and interesting case of perianal mucinous adenocarcinoma in a 56-year-old male initially treated with alternative medicines and local surgery for recurrent fistula in ano of 2 years duration. He presented with complaints of discharging growth in perianal region, painful defecation associated with occasional blood mixed stools of 6 months duration. Incisional biopsy from the ulcer revealed mucinous adenocarcinoma. Contrast enhanced computed tomography (CT) scan and whole body positron emission tomography (PET) scan showed a localized perianal growth which was further confirmed with colonoscopy. With no pre-set treatment protocol for this rare entity, he was managed with neo-adjuvant concurrent chemo-radiation (CCRT) followed by abdominoperineal resection (APR) and adjuvant chemotherapy. Presently he is on 3 monthly follow-up since last 1 year post APR and adjuvant chemotherapy without any evidence of recurrence or distant metastasis. To the best of knowledge, our report may be one of the rarest cases of this disease entity where the duration of anal fistula was merely 2 years in contrast to the established criteria that the fistula precedes carcinoma by at least 10 years.

  14. Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous Adenocarcinoma: A Propensity Score-Matched Study

    PubMed Central

    Sun, Yan-wu; Lin, Hui-ming; Lu, Xing-rong; Huang, Ying; Xu, Zong-bin; Huang, Sheng-hui; Wang, Xiao-jie

    2017-01-01

    Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.

  15. Mucinous adenocarcinoma of perianal region: an uncommon disease treated with neo-adjuvant chemo-radiation

    PubMed Central

    Sharma, Neelam; Dutta, Vibha; Bisht, Niharika; Pandya, Tejas

    2016-01-01

    Mucinous adenocarcinoma of the perianal region is an oncologic rarity posing a diagnostic and therapeutic dilemma for treating oncologists due to very few reported cases without definite therapeutic guidelines. It accounts for 2% to 3% of all gastrointestinal malignancies and are historically known to arise from chronic anal fistulas and ischiorectal or perianal abscesses. We hereby report a sporadic and interesting case of perianal mucinous adenocarcinoma in a 56-year-old male initially treated with alternative medicines and local surgery for recurrent fistula in ano of 2 years duration. He presented with complaints of discharging growth in perianal region, painful defecation associated with occasional blood mixed stools of 6 months duration. Incisional biopsy from the ulcer revealed mucinous adenocarcinoma. Contrast enhanced computed tomography (CT) scan and whole body positron emission tomography (PET) scan showed a localized perianal growth which was further confirmed with colonoscopy. With no pre-set treatment protocol for this rare entity, he was managed with neo-adjuvant concurrent chemo-radiation (CCRT) followed by abdominoperineal resection (APR) and adjuvant chemotherapy. Presently he is on 3 monthly follow-up since last 1 year post APR and adjuvant chemotherapy without any evidence of recurrence or distant metastasis. To the best of knowledge, our report may be one of the rarest cases of this disease entity where the duration of anal fistula was merely 2 years in contrast to the established criteria that the fistula precedes carcinoma by at least 10 years. PMID:28138619

  16. Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

    PubMed Central

    Takanashi, Yusuke; Tsukui, Masaru; Shinmura, Kazuya; Hayakawa, Takamitsu; Takahashi, Tsuyoshi; Neyatani, Hiroshi; Funai, Kazuhito

    2016-01-01

    An extremely rare case of non-mucinous lepidic-predominant invasive adenocarcinoma (LPA) showing extensive aerogenous spread with a pneumonic presentation is reported. A 73-year-old woman was referred to our hospital because of an infiltrative shadow on chest xray. Chest computed tomography revealed extensive ground glass opacities in the right lower lobe, which was accompanied by infiltrative shadow with a pneumonic presentation. Invasive mucinous adenocarcinoma was presumed, and a partial resection of the right lower lobe was done. Histopathological examination revealed lepidic growth-predominant invasive adenocarcinoma with Clara type tumor cells, and there were innumerable aerogenous metastases also consisting of Clara cells. Because Alcian Blue and periodic acid-Schiff staining disclosed no mucus, the tumor was diagnosed as a non-mucinous LPA. The patient showed a poor response to 5 courses of pemetrexed, and she died one year after the diagnosis due to cancer progression. Nonmucinous LPA showed a rare presentation characterized by extensive aerogenous spread followed by a poor prognosis. PMID:28058100

  17. An unusual radiological presentation of mucinous adenocarcinoma of the colon

    PubMed Central

    Swann, Joanna; Kaczynski, Jakub

    2016-01-01

    We report a case of an elderly patient presenting with the left iliac fossa mass. The provisional diagnosis included an inflammatory diverticular mass or sigmoid colon cancer. Interestingly, computed tomography (CT) of the abdomen and pelvis demonstrated the left incarcerated Spigelian hernia containing an inflamed loop of the colon with signs of an early strangulation. However, at operation, a mucinous tumor was found involving the descending and upper sigmoid colon. The tumor eroded through the anterior abdominal wall, which was excised “en bloc.” In the presented case, CT findings suggestive of a benign etiology were misleading. This potentially could have had significant consequences if the patient was treated conservatively. This case highlights that clinical history and examination remain the core components of a safe surgical practice. Clinical judgment cannot be substituted even by the best quality imaging. Therefore, we feel that it is important to share our experience of the successful management of the presented case. PMID:28250979

  18. Well-differentiated mucinous uterine adenocarcinoma predominantly diagnosed as adenoma malignum: a case report with an immunohistochemical analysis.

    PubMed

    Semczuk, Andrzej; Tomaszewski, Jacek; Gogacz, Marek; Obrzut, Bogdan; Rigau, Marina; Lewkowicz, Dorota; Semczuk-Sikora, Anna

    2015-01-01

    Adenoma malignum (AM), also referred to as "minimal deviation adenocarcinoma", is an extremely uncommon variant of highly-differentiated adenocarcinoma of the uterine cervix. The study presented herein describes a case of uterine AM found out after hysteroscopy. An early-stage, well-differentiated mucinous uterine adenocarcinoma was diagnosed post-operatively. A subsequent immunohistochemical assessment of a panel of antibodies was applied, in order to distinguish between female genital tract malignancies.

  19. Contrast-enhanced ultrasound improves accurate identification of appendiceal mucinous adenocarcinoma in an old patient

    PubMed Central

    Shang, Jing; Ruan, Li-tao; Dang, Ying; Wang, Yun-yue; Song, Yan; Lian, Jie

    2016-01-01

    Abstract Background: Adenocarcinoma of appendiceal origin is far rarer than other colorectal carcinomas and its preoperative diagnosis is challenging. To our knowledge, utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. Method: A 61-year-old man presented with abdominal pain in the right lower quadrant for 20 days. In order to fulfill an accurately preoperative diagnosis, he received laboratory and imaging tests such as carcinoembryonic antigen (CEA), computer tomography (CT), CEUS and endoscope. Diagnosis and Intervention: He was initially suspected of suffering appendicitis, while his white blood cell count was normal and carcinoembryonic antigen (CEA) in serum was remarkably increased. Both routine ultrasound and computer tomography (CT) examinations supported suppurative appendicitis. The overall data, however, failed to excluded neoplastic pathology thoroughly. Therefore, CEUS was carried out and showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The result of the follow-up biopsy guided by endoscope was consistent with appendiceal tumor. The patient received laparoscopic right hemicolectomy. Histopathology confirmed as well differentiated mucinous adenocarcinoma of appendix origin. His postoperative course was uneventful, and he had a regular diet again without any complaint. Result: Serum CEA was remarkably increased (12.00 ng/mL). Both routine ultrasound and CT examinations supported suppurative appendicitis. However, CEUS examination showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The follow-up biopsy guided by endoscope and surgical specimens confirmed as well differentiated mucinous adenocarcinoma of appendix origin. Conclusion: Most mucinous adenocarcinoma mimicking appendicitis results in difficult diagnosis preoperatively. Clinician and radiologist should be

  20. A Rare Case of Mucinous Adenocarcinoma of the Colon Presenting as Ileoileal Intussusception in an Adult

    PubMed Central

    Chand, Prakash; Patel, Avani A.; Cervellione, Kelly L.; Sulh, Muhammed

    2012-01-01

    Intussusception is the cause of around 1% of all bowel obstructions in adults. Unlike in children, where intussusception is most often idiopathic in nature, cases in adults usually have an identifiable etiology, most commonly malignancy. Symptoms are usually non-specific, but timely identification and management is crucial due to high rates of carcinoma as the lead point of intussusception. Here we present a rare case of mucinous adenocarcinoma of the colon that presented as ileoileal intussusception. Diagnostic and treatment issues are also discussed. PMID:22454643

  1. Goblet cells carcinoid with mucinous adenocarcinoma of the vermiform appendix: a step towards the unitary intestinal stem cell theory?

    PubMed

    Gravante, G; Yahia, S; Gopalakrishnan, K; Mathew, G

    2014-06-01

    Associations of various histotypes in appendiceal neoplasms may help elucidate the histogenesis of such uncommon tumors. We present the fourth published case of Goblet Cell Carcinoid (GCC) associated with mucinous adenocarcinoma of the appendix. This association has been described only for GCC and not for classic appendix carcinoids which are thought to originate from neuroendocrine-committed cells. The GCC-mucinous association adds more towards the theory of a pluripotent intestinal stem cell with amphicrine possibilities of differentiation.

  2. [Mucinous adenocarcinoma of the nose and paranasal sinuses, an occupational disease?].

    PubMed

    Rüttner, J R; Makek, M

    1985-12-21

    In Great Britain and other countries there have been reports of an increased frequency of adenocarcinoma of the nose and paranasal sinuses, mimicking histologically mucinous colonic carcinoma, among workers exposed to wood dust and workers in the leather industry. No such cases have been reported so far in Switzerland. 31 patients with this type of adenocarcinoma of the nose and paranasal sinuses observed between 1953 and 1984 have been reviewed. In 13 of these patients there was occupational exposure to wood dust, and 4 were shoemakers. The study suggests an association of this type of nasal carcinoma with occupational exposure to wood dust and leatherwork. The nature of the postulated carcinogen is unknown. The authors propose further investigations to define the magnitude of the cancer risk associated with exposure to wood dust and leather.

  3. Colorectal adenocarcinoma with mucinous component: relation of MMP-13, EGFR, and E-cadherin expressions to clinicopathological features and prognosis.

    PubMed

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira Kamal; Aziz, Azza Abdel

    2015-06-01

    The aim of this study was to compare colorectal adenocarcinoma with mucinous component, ordinary adenocarcinoma (OA) and mucinous adenocarcinoma (MA) regarding clinicopathological parameters, survival, EGFR, MMP-13, and E-cadherin. We studied tumor tissue specimens from 28 patients with adenocarcinoma with mucinous component, 47 with OA, and 56 with MA, who underwent radical surgery from January 2007 to January 2012 at the Gastroenterology Centre, Mansoura University, Egypt. High density manual tissue microarrays were constructed and immunohistochemistry for EGFR, MMP-13, and E-cadherin was done. Colorectal adenocarcinoma with mucinous component (AWMC) was significantly associated with more perineural invasion, lower EGFR, and MMP-13 expressions than OA, with no difference in E-cadherin expression. Conversely, only microscopic abscess formation was significantly more with colorectal AWMC than MC with no difference in EGFR, MMP-13 and E-cadherin expression between both groups. Colorectal AWMC showed a better survival than MA with no difference with OA. In a univariate analysis, EGFR, MMP-13, and E-cadherin expressions did not show a significant impact on disease-free or overall survival in patients with colorectal AWMC. Colorectal AWMC remains a vague entity that resembles OA in some clinicopathological and molecular respects as well as MA.

  4. [Perianal mucinous adenocarcinoma. A further reason for histological study of anal fistula or anorectal abscess].

    PubMed

    Marti, L; Nussbaumer, P; Breitbach, T; Hollinger, A

    2001-05-01

    A 39-year-old man came to us for surgical treatment of a hidradenitis suppurativa. Upon excision of a perianal abscess, the diagnosis of a rare tumor, a perianal mucinous adenocarcinoma (pT4, pN 1, MO), was made. An abdominoperineal resection was performed, followed by a combination of adjuvant radiation and chemotherapy. A year after the operation, the patient is doing well without any signs of recurrence. This carcinoma probably arises in the anal glands. It often presents as a perirectal abscess and/or an anal fistula. Therefore, the diagnosis is often delayed. At presentation, the tumor is bigger than 5 cm in diameter in 80% of the cases, and the prognosis is poor. It metastasizes mostly to the superficial inguinal or to the retrorectal lymph nodes. There are only case reports and no comparative studies in the literature. In the last 10 years, the carcinoma has mostly been treated by neoadjuvant radiation and chemotherapy, followed by abdominoperineal resection. Since then, the median survival has increased to 3 years. This is the first case report of a combination of a perianal mucinous adenocarcinoma with a hidradenitis suppurativa.

  5. A rare case of metachronous penile and urethral metastases from a rectal mucinous adenocarcinoma.

    PubMed

    Christodoulidou, Michelle; Sahdev, Varun; Muneer, Asif; Nigam, Raj

    2015-11-05

    Metastatic lesions in the penis are uncommon in patients with prostate or bladder cancer but penile metastatic lesions from rectal tumours are rare with only 65 cases reported in the literature. We describe the case of a 70-year-old man who developed metastatic lesions within his corpus cavernosum 2 years after being diagnosed and treated for a mucinous adenocarcinoma of the rectum and a year after a wedge resection of an isolated lung metastasis. He proceeded with total penectomy and intraoperatively two skip lesions were also found within the wall of his urethra; histological analysis proved that these were also metastatic lesions. A perineal urethrostomy was formed with the remaining macroscopically healthy urethra. He made a good recovery from his operation and continued his treatment under the oncology team.

  6. Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

    PubMed

    Foda, Abd AlRahman M; AbdelAziz, Azza; El-Hawary, Amira K; Hosni, Ali; Zalata, Khalid R; Gado, Asmaa I

    2015-08-01

    Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

  7. K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary.

    PubMed Central

    Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.

    1991-01-01

    To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759

  8. Clinicopathological and immunohistochemical features of lung invasive mucinous adenocarcinoma based on computed tomography findings

    PubMed Central

    Shimizu, Katsuhiko; Okita, Riki; Saisho, Shinsuke; Maeda, Ai; Nojima, Yuji; Nakata, Masao

    2017-01-01

    Background We performed an analysis to clarify differences in clinicopathological and molecular features of lung invasive mucinous adenocarcinoma (IMA) based on computed tomography (CT) findings and their impact on prognosis. Patients and methods On the basis of CT findings, we divided lung IMA into three subtypes: solid, bubbling, and pneumonic. We then investigated differences in clinicopathological characteristics, prognosis, and the expressions of well-identified biomarkers, including cyclooxygenase-2 (Cox-2), excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), class III beta-tubulin, thymidylate synthase (TS), secreted protein acidic and rich in cysteine (SPARC), programmed cell death-1 ligand-1 (PD-L1), and epidermal growth factor receptor mutation, among the three subtypes. Results A total of 29 patients with resected lung IMA were analyzed. Compared with the solid or bubbling type, the pneumonic type had a higher proportion of symptoms, a larger tumor size, a higher pathological stage, and a significantly worse prognosis. The immunohistochemical findings tended to show high expression of RRM1, class III beta-tubulin, and Cox-2 in the tumor and of SPARC in the stroma, but not of ERCC1, TS, and PD-L1 in the tumor. None of the biomarkers with high expression levels in the tumor were prognostic biomarkers, but the expression of SPARC in the stroma was correlated with a poor outcome. Conclusion Clinical and pathological features, in conjunction with molecular data, indicate that IMA should be divided into different subgroups. In our results, the pneumonic type was correlated with a significantly worse outcome. Further studies should be performed to confirm our conclusion and to explore its molecular implications. PMID:28096683

  9. A Rare Case of Intraductal Papillary Mucinous Neoplasm of the Biliary Duct in a Patient with Prostate Adenocarcinoma

    PubMed Central

    Parekh, Ravish; Krol, Gregory; Piraka, Cyrus; Batra, Surinder

    2016-01-01

    Intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing papillary neoplasms of the pancreatic or biliary ductal system that exhibit variable cellular atypia and cause ductal dilation. There are few reported cases of IPMN arising from the biliary tree in the literature. It has a higher propensity to undergo malignant transformation compared to IPMN arising from the pancreatic duct. An 80-year-old male underwent cross-sectional tomography (CT) imaging of the abdomen for evaluation of prostate adenocarcinoma, which revealed an incidental 2.3 × 2.7 cm soft tissue mass centered at the porta hepatis with diffuse dilatation of the left intrahepatic biliary ductal system and mild prominence of the right intrahepatic ductal system. Endoscopic ultrasound showed 2 adjacent hilar masses involving the common hepatic duct and the left hepatic duct with protrusion of the tissue into the lumen of the duct and upstream ductal dilatation. Endoscopic retrograde cholangiopancreatography revealed a large filling defect in the common hepatic duct extending into the left hepatic duct. A large amount of clot and soft tissue with a fish-egg appearance was retrieved. The patient underwent left hepatic lobectomy, radical resection of the common hepatic duct with Roux-en-Y hepaticojejunostomy to the right hepatic duct. Histopathological examination of the resected specimen revealed intraductal papillary mucinous neoplasm with diffuse high-grade dysplasia. Follow-up CT scan of the abdomen 2 months after the surgery was negative for any masses. PMID:28100995

  10. Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

    PubMed

    Foda, Abd Al-Rahman Mohammad; Mohammad, Mie Ali; Abdel-Aziz, Azza; El-Hawary, Amira Kamal

    2015-06-01

    Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.

  11. Coexistence of mature cystic teratoma and adenocarcinoma in situ within atypical proliferative mucinous tumour of ovary--a case report of 35-year-old woman.

    PubMed

    Wincewicz, A; Lewitowicz, P; Adamczyk-Gruszka, O; Sulkowski, S; Kanczuga-Koda, L; Koda, M

    2015-01-01

    Combined ovarian tumors are found in common pathologic practice due to amazing potential of ovarian tissue to copy almost every tissue of human body and imitate many neoplasms of various other organs in a very flexible way. A multicystic tumor is presented in this case report of 35-year-old woman. It consisted of a cyst with sebum and hair and cavities with papillomatous projections and mucus. The ovarian tumor was diagnosed a mature cystic teratoma presenting mainly as dermoid cyst and mucinous adenocarcinoma in situ, arising within atypical proliferative mucinous tumor. This report demonstrates how histoformative properties are reflected in ovarian tumorigenesis. Such a stunning histoformativity makes ovaries the possible site of primary origin for malignant tumors that mimic extra ovarian differentiation. In the authors' point of view, the diagnosis of primary ovarian mucinous tumor within cystic teratoma is firm, whenever simultaneous extraovarian involvement by mucinous neoplasm is excluded.

  12. Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.

    PubMed

    Shiratsu, Kazuo; Higuchi, Kayoko; Nakayama, Jun

    2014-01-01

    Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma.

  13. The Case of an Elderly Male Patient with Unknown Primary Mucinous Adenocarcinoma within Presacral Teratoma (Teratoma with Malignant Transformation)

    PubMed Central

    Cokmert, Suna; Koca, Emine; Bulut, Naki; Gul, Suha; Yilmaz, Nevin

    2015-01-01

    Teratomas are rarely seen in adults, and presacral region is an area where they rarely settle in. Similarly, only about 1% of teratomas show malignant transformation. Malignant transformation is often associated with the area where teratoma settles in. Malignant transformation of mediastinal teratomas is more frequent than the ones located in retroperitoneal area and gonad. They most commonly show rhabdomyosarcoma, primitive neuroectodermal tumor, enteric adenocarcinoma, and leukemia transformation. In teratomas showing malignant transformation, the clinical course is aggressive; and survival of patients with metastatic disease is very low. The primary treatment of teratomas with malignant transformations is surgical. Effect of radiotherapy and chemotherapy is not clear in patients, to whom surgical operation cannot be applied, or those who are with residual tumor, even if surgical operation can be applied to them, or those who are at metastatic stage. In this paper, we presented a 76-year-old male patient due to the histologic diagnosis of mucinous adenocarcinoma within teratoma, in whom approximately 7 cm presacral mass was found during the radiographic examination made by the reason of low back pain and pelvic pain. PMID:25874143

  14. A New Hitherto Unreported Histopathologic Manifestation of Mammary Analogue Secretory Carcinoma: "Masked MASC" Associated With Low-grade Mucinous Adenocarcinoma and Low-grade In Situ Carcinoma Components.

    PubMed

    Petersson, Fredrik; Michal, Michael; Kazakov, Dmitry V; Grossmann, Petr; Michal, Michal

    2016-10-01

    We present a salivary gland tumor of the parotid gland in a 54-year-old woman, which contained a minor mammary analogue secretory carcinoma (MASC) component (20%) intermixed with a morphologically entirely different mucinous adenocarcinomatous component that comprised 80% of the tumor mass and a morphologically nondescript low-grade intraductal carcinoma (in situ) component. On fluorescence in situ hybridization, a break in the ETV6 gene was documented in the mucinous adenocarcinomatous, the conventional MASC, and the intraductal (in situ) components. RT-PCR failed to reveal an ETV6-NTRK3 fusion. The entire conventional MASC and only rare mucinous adenocarcinoma tumor cells were mammaglobin positive, whereas the low-grade intraductal carcinoma (in-situ) component was negative. S-100 protein stained only the MASC component.

  15. Primary Mucinous Adenocarcinoma of the Urinary Bladder with Signet-Ring Cells: Description of an Uncommon Case and Critical Points in Its Management

    PubMed Central

    Amorim Aita, Giuliano; Amorim Aita, Daniele

    2016-01-01

    We present an uncommon case of mucinous adenocarcinoma of the bladder (MAB) with signet-ring cells extensively infiltrating prostate gland and pelvic/retroperitoneal lymph node stations and not responsive to usual systemic chemotherapy regimens. This case highlights the important features of MAB including the pattern of tumor spread, the tendency for initial misdiagnosis, and the importance of immunohistochemical study in order to define its primary origin from the bladder and choose the most appropriate treatment since the beginning. PMID:28078160

  16. Signet-ring cell (mucin-producing) adenocarcinomas of minor salivary glands.

    PubMed

    Ghannoum, Julien E; Freedman, Paul D

    2004-01-01

    We report seven cases of minor salivary gland carcinomas characterized by the marked presence of mucin-containing signet-ring cells. These tumors were distinctive in their microscopic appearance and displayed features not seen in any other type of salivary gland malignancy. They typically exhibited invasive growth by narrow parallel strands, randomly scattered small nests, or individually infiltrating cells. Solid, cribriform, or targetoid areas were absent, as well as papillary components. Ductal differentiation was minimal, and seen in only four cases. Degrees of cellularity varied from one area to another. The tumors were cytologically bland. We think that these tumors represent a unique subset of intraoral minor salivary gland carcinomas.

  17. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis.

    PubMed

    Besmer, Dahlia M; Curry, Jennifer M; Roy, Lopamudra D; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y; Gendler, Sandra J; Mukherjee, Pinku

    2011-07-01

    MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro.

  18. A 57-year-old Brazilian woman with a giant mucinous cystadenocarcinoma of the ovary: a case report

    PubMed Central

    2014-01-01

    Introduction Giant cystadenocarcinomas of the ovary are rarely described conditions. Case presentation The authors describe a 57-year-old Brazilian woman who presented with an increase in abdominal girth in February 2003. Imaging studies showed a giant abdominal pelvic mass with probable origin in the right ovary. Cancer antigen-125 was elevated, while carcinoembrionic antigen and alpha-fetoprotein were normal. Total abdominal hysterectomy, bilateral salpingoophorectomy and omentectomy were done. The mass weighed 40Kg, and the histopathology study revealed a mucinous cystadenocarcinoma. She underwent chemotherapy with paclitaxel and cisplatin with no side effects. Under follow-up for more than 10 years, she is asymptomatic and with normal imaging and laboratory parameters, including the cancer antigen-125 marker. Conclusion This huge tumor evolved for a long time unsuspected and without metastases in a patient from a developing region. The diagnostic and management challenges posed by this unexpected and unusual presentation of an ovarian cystadenocarcinoma are discussed. PMID:24594205

  19. Oncogenic function and clinical implications of SLC3A2-NRG1 fusion in invasive mucinous adenocarcinoma of the lung

    PubMed Central

    Shin, Dong Hoon; Lee, Donghoon; Wan Hong, Dong; Hyun Hong, Seung; Hwang, Jung-Ah; Il Lee, Byung; You, Hye Jin; Kook Lee, Geon; Kim, In-Hoo; Lee, Yeon-Su; Han, Ji-Youn

    2016-01-01

    The neuregulin 1 (NRG1) fusion is a recently identified novel driver oncogene in invasive mucinous adenocarcinoma of the lung (IMA). After identification of a case of SLC3A2-NRG1 in a patient with IMA, we verified this fusion gene in a cohort of 59 patients with IMA. Targeted cancer panel sequencing and RT-PCR identified the possible coexistence of other driver oncogenes. Among 59 IMAs, we found 16 NRG1 fusions (13 SLC3A2-NRG1 and 3 CD74-NRG1). Of 16 patients with NRG1 fusions, concurrent KRAS codon 12 mutations were found in 10 cases. We also found concurrent NRAS Q61L mutation and EML4-ALK fusion in additional two cases with NRG1 fusions. When comparing overall survival (OS) according to the presence of NRG1 fusions showed that patients harboring NRG1 fusions had significantly inferior OS than those without NRG1 fusions (hazard ratio = 0.286; 95% confidence interval, .094 to .865). Ectopic expression of the SLC3A2-NRG1 fusion in lung cancer cells increased cell migration, proliferation and tumor growth in vitro and in xenograft models, suggesting oncogenic function for the fusion protein. We found that the SLC3A2-NRG1 fusion promoted ERBB2-ERBB3 phosphorylation and heteroduplex formation and activated the downstream PI3K/AKT/mTOR pathway through paracrine signaling. These findings suggested that the SLC3A2-NRG1 fusion was a driver in IMA with an important prognostic impact. SLC3A2-NRG1 should be considered a therapeutic target for patients with IMA. PMID:27626312

  20. Mucinous Cystadenocarcinoma in a Horse Shoe Kidney Masquerading as Giant Hydronephrosis – A Case Report: Diagnostic Challenges, Lessons Learnt and Review of Literature

    PubMed Central

    Joseph, Leena Dennis; Swaminathan, Rajendiran; Kripesh, Gokul; Sekar, Hariharasudhan

    2016-01-01

    Primary epithelial tumour of the renal pelvis is a rare entity. So far, very few cases are reported in literature. Of these, mucin secreting adenocarcinomas are distinctly rare. However, mucinous cystadenocarcinoma, that too arising in a horse shoe kidney is extremely rare to be reported. Mucinous cystadenomas and carcinomas arising from the renal pelvis are regarded to be secondary to a metaplastic change in the urothelium. Here, we present a case of a 51-year-old male, who complained of abdominal pain, palpable abdominal mass, haematuria along with passage of mucoid material in the urine, with a very poorly functioning kidney. A pre-operative diagnosis of horse shoe kidney with pelvi ureteric junction obstruction and a poorly functioning kidney was made. Intraoperative findings and frozen section biopsy were suggestive of mucin secreting cystic mass and a right heminephrectomy was done. The final histopathology was suggestive of mucinous cystadenocarcinoma of the renal pelvis of the right moiety. This case is presented for its rarity, diagnostic challenges faced and the lessons learnt, stressing on the need for having a high index of clinical suspicion in making such diagnosis. PMID:28050435

  1. Salivary gland tumor "wishes" to add to the next WHO Tumor Classification: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

    PubMed

    Gnepp, Douglas R

    2014-03-01

    This review is a continuation of suggested tumor additions to the next WHO Tumor Classification. The author will focus on four salivary gland entities that have recently become accepted in the literature as new neoplastic entities: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

  2. Mucin (MUC) expression in EUS-FNA specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma

    PubMed Central

    Higashi, Michiyo; Yokoyama, Seiya; Yamamoto, Takafumi; Goto, Yuko; Kitazono, Ikumi; Hiraki, Tsubasa; Taguchi, Hiroki; Hashimoto, Shinichi; Fukukura, Yoshihiko; Koriyama, Chihaya; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Jain, Maneesh; Batra, Surinder K.; Yonezawa, Suguru

    2015-01-01

    Objectives The aim of this study was to further examine the utility of mucin expression profiles as prognostic factors in PDAC. Methods Mucin (MUC) expression was examined by immunohistochemistry (IHC) analysis in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens obtained from 114 patients with PDAC. The rate of expression of each mucin was compared with clinicopathologic features. Results The expression rates of mucins in cancer lesions were MUC1, 87.7%; MUC2, 0.8%; MUC4, 93.0%; MUC5AC, 78.9%; MUC6, 24.6%; and MUC16, 67.5%. MUC1 and MUC4 were positive and MUC2 was negative in most PDACs. Patients with advanced stage of PDAC with MUC5AC expression had a significantly better outcome than those who were MUC5AC-negative (P=0.002).With increasing clinical stage, total MUC6 expression decreased (P for trend=0.001) and MUC16 cytoplasmic expression increased (P for trend=0.02). The prognosis of patients with MUC16 cytoplasmic expression was significantly poorer than those without this expression. Multivariate survival analysis revealed that MUC16 cytoplasmic expression was a significant independent predictor of a poor prognosis after adjusting for the effects of other prognostic factors (P=0.002). Conclusion Mucin expression profiles in EUS-FNA specimens have excellent diagnostic utility and are useful predictors of outcome in patients with PDAC. PMID:25906442

  3. Limited, local, extracolonic spread of mucinous appendiceal adenocarcinoma after perforation with formation of a malignant appendix-to-sigmoid fistula: Case report and literature review

    PubMed Central

    Hakim, Seifeldin; Amin, Mitual; Cappell, Mitchell S

    2016-01-01

    A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum (with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread (stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon. PMID:27784975

  4. Limited, local, extracolonic spread of mucinous appendiceal adenocarcinoma after perforation with formation of a malignant appendix-to-sigmoid fistula: Case report and literature review.

    PubMed

    Hakim, Seifeldin; Amin, Mitual; Cappell, Mitchell S

    2016-10-14

    A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum (with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread (stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon.

  5. Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis

    PubMed Central

    Besmer, Dahlia M.; Curry, Jennifer M.; Roy, Lopamudra D.; Tinder, Teresa L.; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared to both KC and KCM. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9). Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. PMID:21558393

  6. Lung adenocarcinoma with giant cyst formation showing a variety of histologic patterns: a case report

    PubMed Central

    2010-01-01

    Introduction Lung cancer with large cyst formation is relatively rare. This is a case report of a patient with lung cystic adenocarcinoma with multiple histologic patterns. This type of lung adenocarcinoma is believed to be the first reported case in English language medical literature. Case presentation A 60-year-old Japanese woman was admitted to hospital complaining of dyspnea and died of respiratory failure. She had been suffering from lung cancer with pleural effusion for five years. Autopsy analysis revealed lung adenocarcinoma with large cyst formation showing a variety of histologic patterns. Conclusions Autopsy analysis of this atypical case of lung cancer may provide insight and lead to a better understanding of the heterogeneity and clonal expansion of lung adenocarcinoma. PMID:21108775

  7. A male case of an undifferentiated carcinoma with osteoclast-like giant cells originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. A case report and review of the literature.

    PubMed

    Wada, Takeyuki; Itano, Osamu; Oshima, Go; Chiba, Naokazu; Ishikawa, Hideki; Koyama, Yasumasa; Du, Wenlin; Kitagawa, Yuko

    2011-09-08

    We report a rare male case of an undifferentiated carcinoma with osteoclast-like giant cells originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. A 59-year-old Japanese man with diabetes visited our hospital, complaining of fullness in the upper abdomen. A laboratory analysis revealed anemia (Hemoglobin; 9.7 g/dl) and elevated C-reactive protein (3.01 mg/dl). Carbohydrate antigen 19-9 was 274 U/ml and Carcinoembryonic antigen was 29.6 ng/ml. A computed tomography scan of the abdomen revealed a 14-cm cystic mass in the upper left quadrant of the abdomen that appeared to originate from the pancreatic tail. The patient underwent distal pancreatectomy/splenectomy/total gastrectomy/cholecystectomy. The mass consisted of a multilocular cystic lesion. Microscopically, the cyst was lined by cuboidal or columnar epithelium, including mucinous epithelium. Sarcomatous mononuclear cells and multinucleated osteoclast-like giant cells were found in the stroma. Ovarian-type stroma was not seen. We made a diagnosis of osteoclast-like giant cell tumor originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. All surgical margins were negative, however, two peripancreatic lymph nodes were positive. The patient recovered uneventfully. Two months after the operation, multiple metastases occurred in the liver. He died 4 months after the operation.

  8. Mucinous adenocarcinoma of the intestinal type arising from mature cystic teratoma of the ovary: a rare case report and review of the literature

    PubMed Central

    2012-01-01

    Background Mature cystic teratomas (MCTs) are the most common germ cell tumors of the ovary. Malignant tranformation occurs in 1-2% of these neoplasms. Although most of the malignancies arising from MCTs are squamous cell carcinomas, adenocarcinoma of the gastrointestinal type is extremery rare. We herein present a case of adenocarcinoma of the intestinal type arising from a MCT. Case A 49-year-old female underwent surgery for a left ovarian tumor. The histology of the cyst walls revealed a MCT with a few hair shafts and a squamous layer, while another part of the tumor showed adenocarcinoma of the intestinal type. Five years after surgery, she is alive without disease. PMID:23216975

  9. Adenocarcinoma of the urinary bladder.

    PubMed

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma.

  10. Adenocarcinoma of the urinary bladder

    PubMed Central

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

  11. Radiologic findings of urachal mucinous cystadenocarcinoma causing pseudomyxoma peritonei.

    PubMed

    Kebapçı, Mahmut; Saylısoy, Suzan; Can, Cavit; Dündar, Emine

    2012-05-01

    Urachal mucinous cystadenocarcinoma causing pseudomyxoma peritonei is very rare. We report a case of a 59-year-old man with urachal mucinous adenocarcinoma associated with pseudomyxoma peritonei, and our radiologic findings. Ultrasonography revealed a well delineated, large cystic tumor adjacent to the anterior wall of the abdomen. Computed tomography and magnetic resonance imaging revealed a tumor of which the left posterior wall was defective. A large amount of ascites was present in the peritoneal cavity. The ascites caused displacement of the intestinal structures toward the dorsal region. The tumor wall and septa in the ascites were well enhanced on contrast-enhanced images. Radiologically, pseudomyxoma peritonei due to rupture of urachal cystic tumor was considered. The pathologic diagnosis was mucinous adenocarcinoma and pseudomyxoma peritonei.

  12. [Mucinous cystadenocarcinoma of pancreas].

    PubMed

    Davies, Nestor R; Kasparian, Andres C; Viotto, Lucas E; Moreno, Walter A; Gramática, Luis

    2009-01-01

    Mucinous cystadenocarcinoma of the pancreas represents around 6-36% of mucinous cystic neoplasm. The lesions are usually found in the body and tail of the pancreas and are generally solitary with a size range of 6-36 cm. We present a clinical case of a 63 years old patient with abdominal pain and weight loss. We used radiographic imaging studies. It was treated with surgery by distal pancreatectomy with splenectomy and transverse colectomy. Patient was not post operative complications.

  13. The molecular background of mucinous carcinoma beyond MUC2

    PubMed Central

    Simons, Michiel; Halilović, Altuna; van der Post, Rachel S; Bogers, Anna J; Marijnissen‐van Zanten, Monica AJ; de Wilt, Johannes HW; Nagtegaal, Iris D

    2014-01-01

    Abstract The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10–15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background. In this review we identify common molecular and genetic alterations in colorectal MC. MC is characterized by a high rate of MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and PI3K/AKT pathways are significantly higher in MC compared with non‐mucinous adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of microsatellite instability and is more frequently of the CpG island methylator phenotype. Although the majority of MCs arise from the large intestine, this subtype also develops in other organs, such as the stomach, pancreas, biliary tract, ovary, breast and lung. We compared findings from colorectal MC with tumour characteristics of MCs from other organs. In these organs, MCs show different mutation rates in the RAS/RAF/MAPK and PI3K/AKT pathways as well, but a common mucinous pathway cannot be identified. Identification of conditions and molecular aberrations that are associated with MC generates insight into the aetiology of this subtype and improves understanding of resistance to therapies. PMID:27499889

  14. Prevalence and clinical significance of acellular mucin in locally advanced rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy.

    PubMed

    Lim, Seok-Byung; Hong, Seung-Mo; Yu, Chang Sik; Hong, Yong Sang; Kim, Tae Won; Park, Jin-hong; Kim, Jong Hoon; Kim, Jin Cheon

    2013-01-01

    Occasionally, patients with locally advanced rectal adenocarcinoma who receive preoperative chemoradiotherapy (CRT) show acellular mucin in resection specimens that had shown pathologic complete response (pCR), but the clinical and prognostic significance of this finding has been controversial. This study analyzed data from 217 consecutive patients showing pCR to preoperative CRT followed by resection to evaluate the clinicopathologic features and prognostic significance of acellular mucin. Patients were categorized according to the presence of acellular mucin, as identified by pathologic analysis. The clinicopathologic findings and oncologic results were compared. Acellular mucins were identified in 35 (16.1%) of 217 pCR patients. Acellular mucins were found predominantly in male patients (20.8% vs. 9.8%, P=0.039) and in those with mucinous/signet ring cell differentiation (66.7% vs. 15.1%, P=0.008). The presence of acellular mucin was more frequent in patients with a shorter (<42 d) CRT-operation interval (22.6% vs. 10.3%, P=0.017). With a mean follow-up of 41 months (range, 2 to 119 mo), the 3-year overall survival (96.8% with mucin vs. 95.9% without mucin, P=0.314) and the 3-year disease-free survival (97.0% with mucin vs. 93.0% without mucin, P=0.131) did not differ between the groups. The presence of acellular mucin in rectal cancer patients showing pCR to preoperative CRT is associated with male sex and mucinous differentiation and does not have a significant impact on oncologic outcomes. Acellular mucins are also associated with the CRT-operation interval as a phenomenon of time-dependent response to CRT.

  15. Salivary Mucin 19 Glycoproteins

    PubMed Central

    Culp, David J.; Robinson, Bently; Cash, Melanie N.; Bhattacharyya, Indraneel; Stewart, Carol; Cuadra-Saenz, Giancarlo

    2015-01-01

    Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19−/− mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19−/− mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19−/− mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19−/− mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed. PMID:25512380

  16. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  17. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC.

  18. R1: Immunohistochemical study of mucins in human intestinal spirochetosis.

    PubMed

    Ogata, Sho; Shimizu, Ken; Tominaga, Susumu; Nakanishi, Kuniaki

    2017-02-08

    Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?". Using antibodies for MUCs 1, 2, 4, 5 AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)". Results were analysed for four categories of lesions, and associations between MUC expression and spirochetal presence were also analysed. In the "specimens without polyps or adenocarcinoma" category: high (+) MUC2-positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category: in HIS (vs. control), the MUC5AC-positivity rate was lower, while high (+) MUC4-positivity was more frequent. In the conventional adenoma category: in HIS (vs. control), the MUC1-positivity rate was lower, while both high (+) MUC2-positivity and high (+) MUC5AC-positivity were less frequent. In the adenocarcinoma category: high (+) MUC2-positivity was more frequent in HIS than in control. Among the above mucins, only MUC1-positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin-expression profile in humans.

  19. Metastatic adenocarcinoma to the brain: MR with pathologic correlation

    SciTech Connect

    Carrier, D.A. ); Mawad, M.E.; Kirkpatrick, J.B.; Schmid, M.F. )

    1994-01-01

    To describe the appearance on T2-weighted scans of metastatic adenocarcinoma to the brain and to show that the hypointensity frequently associated with these lesions is not related to the presence of mucin, blood products, iron, or calcium. The MR scans of 14 patients with metastatic adenocarcinoma to the brain were reviewed retrospectively. The signal intensity on T2-weighted scans of the solid enhancing portion of the tumors was compared with white matter. Histologic examination of the surgical specimens included special stains to search for calcium, mucin, and iron. Eight of nine surgical and all six nonsurgical lesions were either iso- or hypointense to white matter on T2-weighted scans. There was no correlation with tumor histology or the presence of mucin, blood products, iron, or calcium. The presence of a hypointense intraaxial mass on T2-weighted scans strongly suggests the possibility of metastatic adenocarcinoma. The MR appearance is not explained by the presence of mucin, blood products, iron, or calcium. This phenomenon most likely reflects the relaxation parameters of the tissue from which the metastasis arose. 21 refs., 3 figs., 1 tab.

  20. Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation.

    PubMed

    Whitcomb, Emma; Liu, Xiuli; Xiao, Shu-Yuan

    2014-02-01

    Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

  1. Diarrhea Concealing a Duodenal-Cecal Fistula Secondary to Appendiceal Mucinous Neoplasm

    PubMed Central

    Cheung, Amanda; Prather, Charlene; Lai, Jinping

    2017-01-01

    Primary mucinous adenocarcinoma of the appendix is a rare gastrointestinal malignancy. Fistulous tract formation is a complication that is cited in literature. An 85-year-old man with multiple comorbidities presented with several weeks of persistent non-bloody diarrhea. Laboratory work-up was non-diagnostic. Abdominal imaging with barium contrast showed an enterocolonic fistulous tract extending from the duodenum to the cecum involving an enlarged appendiceal mass. Subsequent biopsy confirmed mucinous appendiceal neoplasm with peritoneal spread to the liver and mesentery. This is the first report describing an enterocolonic fistula formation resulting from this malignancy. PMID:28138447

  2. Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.

    PubMed

    Sentani, Kazuhiro; Tashiro, Takashi; Uraoka, Naohiro; Aosaki, Yoriyuki; Yano, Satomi; Takaeko, Fumio; Yasui, Wataru

    2012-07-01

    Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation.

  3. Intraductal papillary mucinous neoplasms of the pancreas (IPMNs): epidemiology, diagnosis and future aspects.

    PubMed

    Konstantinou, Froso; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2013-03-10

    Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are potentially malignant intraductal epithelial neoplasms which consist of columnar, mucin-containing cells and arise from the epithelium of the main pancreatic duct or its branches. IPMNs as well as pancreatic intraepithelial neoplasias (PanINs) and mucinous cystic neoplasms represent noninvasive precursors of invasive ductal adenocarcinoma of the pancreas. The diagnosis of IPMNs includes radiographic (CT scanning, MRI, MRCP) and endoscopic evaluation (ERCP, EUS), PET, as well as serum tumor markers and molecular markers. The Sendai Consensus Guidelines help guide surgical resection for patients with IPMN. The follow-up of these patients, as well as of those who do not undergo surgical resection, is of great importance, since patients with IPMN appear to be at risk for other malignancies. Herein, the authors summarize the data presented at the 2013 ASCO Gastrointestinal Cancers Symposium regarding incidence and clinicopathological characteristics of IPMN (Abstracts #324, #187 and #179).

  4. Mucins and inflammatory bowel disease

    PubMed Central

    Shirazi, T.; Longman, R.; Corfield, A.; Probert, C.

    2000-01-01

    There is a layer of mucus lining the gastrointestinal tract, which acts as both a lubricant and as a physical barrier between luminal contents and the mucosal surface. The mucins that make up this layer consist of a protein backbone with oligosaccharides attached to specific areas of the protein core. These areas are called the variable number tandem repeat regions. The degree of glycosylation of the mucins is central to their role in the mucus barrier. The oligosaccharides are variable and complex. It has been demonstrated that the degree of sulphation and sialylation and the length of the oligosaccharide chains all vary in inflammatory bowel disease. These changes can alter the function of the mucins. Mucins are broadly divided into two groups, those that are secreted and those that are membrane bound. The major mucins present in the colorectum are MUC1, MUC2, MUC3, and MUC4.
Trefoils are a group of small peptides that have an important role in the mucus layer. Three trefoils have been demonstrated so far. They seem to play a part in mucosal protection and in mucosal repair. They may help to stabilise the mucus layer by cross linking with mucins to aid formation of stable gels. Trefoils can be expressed in the ulcer associated cell lineage, a glandular structure that can occur in the inflamed mucosa. There seem to be differences in the expression of trefoils in the colon and the small bowel, which may imply different method of mucosal repair.


Keywords: mucins; trefoil; Crohn's disease; colitis PMID:10908374

  5. Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy

    PubMed Central

    2012-01-01

    Background Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients. Methods In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR. Results In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p < 0.0062), CXCL1 (p < 0.00014) and CXCL2 (p < 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC. Conclusions Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC. PMID:23102107

  6. Biochemical and ultrastructural correlations of calreticulin and thioredoxin expression in breast mucinous carcinoma and infiltrating ductal carcinoma non-special type.

    PubMed

    Baltatzis, G E; Gaitanarou, H; Arnogianaki, N; Misitzis, J; Voloudakis-Baltatzis, I E

    2011-02-01

    Mucinous infiltrating invasive ductal adenocarcinoma consists of 2-4% invasive breast cancer, but is a very interesting type due to its macroscopic similarity to non-special-type (NST) ductal carcinoma. The macroscopic similarity of mucinous and infiltrating ductal carcinoma NST adenocarcinomas consists of a loose and edematous stroma, which is often seen in portions of NST carcinoma and may mimic the mucin pools of mucinous carcinoma. In this study the authors examined the ultrastructural differences between mucinous carcinoma and infiltrating ductal carcinoma NST. They also examined the protein expression of the tissues by 2D electrophoresis due to their belief that from the results of these two levels it is possible to understand the changes that take place both in the ultrastructural and biochemical levels in these two types of breast cancer. The ultrastructural results from mucinous carcinoma have shown many changes in cytoplasmic organelles in comparison to normal samples, depending on the grade and the number of metastatic lymph nodes. At the 2D elecrophoresis level the authors studied two interesting polypeptides, calreticulin and thioredoxin. Both of these proteins were found in patterns of fibroadenoma, mucinous carcinoma, and NST carcinoma, but with different quantitative expression among them. In the future the quantitative differences of these two proteins may provide specific tumor markers for these two types of carcinoma.

  7. Histologic characteristics of thymic adenocarcinomas: Clinicopathologic study of a nine-case series and a review of the literature.

    PubMed

    Kwon, Ah-Young; Han, Joungho; Chu, Jinah; Choi, Yong Soo; Jeong, Byeong-Ho; Ahn, Myung-Ju; Ahn, Yong Chan

    2017-02-01

    Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature. Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract. Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features. In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with

  8. Cell patterning with mucin biopolymers

    PubMed Central

    Crouzier, T.; Jang, H.; Ahn, J.; Stocker, R.; Ribbeck, K.

    2014-01-01

    The precise spatial control of cell adhesion to surfaces is an endeavor that has enabled discoveries in cell biology and new possibilities in tissue engineering. The generation of cell-repellent surfaces currently requires advanced chemistry techniques and could be simplified. Here we show that mucins, glycoproteins of high structural and chemical complexity, spontaneously adsorb on hydrophobic substrates to form coatings that prevent the surface adhesion of mammalian epithelial cells, fibroblasts, and myoblasts. These mucin coatings can be patterned with micrometer precision using a microfluidic device, and are stable enough to support myoblast differentiation over seven days. Moreover, our data indicate that the cell-repellent effect is dependent on mucin-associated glycans because their removal results in a loss of effective cell-repulsion. Last, we show that a critical surface density of mucins, which is required to achieve cell-repulsion, is efficiently obtained on hydrophobic surfaces, but not on hydrophilic glass surfaces. However, this limitation can be overcome by coating glass with hydrophobic fluorosilane. We conclude that mucin biopolymers are attractive candidates to control cell adhesion on surfaces. PMID:23980712

  9. Analysis of assembly of secreted mucins.

    PubMed

    Johansson, Malin E V; Hansson, Gunnar C

    2012-01-01

    Studies of assembly and secretion of gel-forming mucins are complex. The pulse-chase methods for mucins described here include metabolic radiolabeling and labeling in animals with azido-GalNAc. The labeled mucins are analyzed by composite agarose-polyacrylamide gel electrophoresis and autoradiography or by mucus-preserving tissue fixation and Click-iT(®) chemistry.

  10. Mucin-producing bile duct carcinoma arising from primary sclerosing cholangitis: a case report.

    PubMed

    Yokomuro, Shigeki; Arima, Yasuo; Mizuguchi, Yoshiaki; Shimizu, Tetsuya; Kawahigashi, Yutaka; Kannda, Tomohiro; Arai, Masao; Uchida, Eiji; Akimaru, Koho; Tajiri, Takashi

    2007-02-01

    A 60-year-old woman with primary sclerosing cholangitis (PSC) and high levels of ALP, gamma-GTP, and DUPAN-2 was admitted to our institution for examination. The patient did not have ulcerative colitis or pancreatic intraductal papillary mucinous neoplasm. Imaging studies revealed atypical dilation of bile ducts in the left lobe of the liver. Repeated cytologic examinations of the bile showed atypical cells consistent with adenocarcinoma. The patient underwent extended resection of the left lobe of the liver and was found to have intraductal papillary carcinoma with associated mucin-producing bile duct carcinoma. This carcinoma fills dilated bile duct lumens with mucin. This tumor differs morphologically from typical cholangiocarcinoma, which is usually seen in the late stages of PSC. Just one case of mucin-producing bile duct carcinoma arising from PSC has been reported worldwide. The patient has had no signs of recurrence after 27 months. Patients with mucin-producing bile duct carcinoma, as in the case of its pancreatic counterpart, may have a better prognosis and a higher survival rate than patients with typical cholangiocarcinomas.

  11. Histological subtypes of solitary pulmonary nodules of adenocarcinoma and their clinical relevance

    PubMed Central

    Hu, Hui-Di; Wan, Ming-Yue; Xu, Chun-Hua; Zhan, Ping; Zou, Jue; Zhang, Qian-Qian

    2013-01-01

    Objective To explore the histological subtypes of solitary pulmonary nodules (SPNs) of invasive adenocarcinoma and their clinical relevance. Methods A total of 188 patients with pathologically confirmed invasive adenocarcinoma in our hospital from January 2007 to December 2011 were enrolled in this study. In accordance with the new classification of lung adenocarcinoma, all the histological sections were reviewed and classified, and the clinical data were collected and analyzed. Results Of these 188 patients who had been initially diagnosed as SPNs of adenocarcinoma, there were 6 cases of lepidic predominant adenocarcinoma (LPA), 71 cases of acinar predominant adenocarcinoma (APA), 74 cases of papillary predominant adenocarcinoma (PPA), 15 cases of micorpapillary predominant adenocarcinoma (MPA), and 22 cases of solid predominant adenocarcinoma (SPA) with mucin production. The incidence of lymph node metastasis was 80.0% and 81.8% in MPA and SPA, respectively, which was significantly higher than those in LPA, APA, and PPA (all P<0.01). The incidence of LPA was 83.3% (5/6) in women, which was significantly higher than that in men (P=0.037). Conclusions According to the new classification, MPA and SPA have high incidence of lymph node metastasis. LPA is more likely to occur in women. Sub-typing of the lung adenocarcinoma based on the newest international classification criteria is helpful to identify the clinical features of this disease. PMID:24409363

  12. Adenocarcinoma in an ano-vaginal fistula in Crohn's disease

    PubMed Central

    Alfa-Wali, Maryam; Atinga, Angela; Mohsen, Yasser; Anthony, Andrew; Myers, Alistair

    2013-01-01

    INTRODUCTION Fistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASE We present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSION Various pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSION Better detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum. PMID:23702362

  13. The Management and Prognostic Prediction of Adenocarcinoma of Appendix

    PubMed Central

    Xie, Xin; Zhou, Zhangjian; Song, Yongchun; Li, Wenhan; Diao, Dongmei; Dang, Chengxue; Zhang, Hao

    2016-01-01

    Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation. PMID:27982068

  14. Laparoscopic Diagnosis of Adenocarcinoma of the Appendix Mimicking Serous Papillary Adenocarcinoma of the Peritoneum

    PubMed Central

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020

  15. A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome.

    PubMed

    Kim, Eun Na; Kim, Gu-Hwan; Kim, Jiyoon; Park, In Ah; Shin, Jin Ho; Chai, Yun; Kim, Kyu-Rae

    2017-03-01

    We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1-7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations.

  16. A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome

    PubMed Central

    Kim, Eun Na; Kim, Gu-Hwan; Kim, Jiyoon; Park, In Ah; Shin, Jin Ho; Chai, Yun; Kim, Kyu-Rae

    2017-01-01

    We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1–7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations. PMID:27550049

  17. Mucin Binding Reduces Colistin Antimicrobial Activity

    PubMed Central

    Huang, Johnny X.; Blaskovich, Mark A. T.; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G.; Butler, Mark S.

    2015-01-01

    Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance. PMID:26169405

  18. Mucin Binding Reduces Colistin Antimicrobial Activity.

    PubMed

    Huang, Johnny X; Blaskovich, Mark A T; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G; Butler, Mark S; Montgomery, A Bruce; Cooper, Matthew A

    2015-10-01

    Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance.

  19. Particle tracking microrheology of purified gastrointestinal mucins.

    PubMed

    Georgiades, Pantelis; Pudney, Paul D A; Thornton, David J; Waigh, Thomas A

    2014-04-01

    The rheological characteristics of gastric and duodenal mucin solutions, the building blocks of the mucus layer that covers the epithelia of the two organs, were investigated using particle tracking microrheology. We used biochemically well characterized purified porcine mucins (MUC5AC and MUC2) as models for human mucins, to probe their viscoelasticity as a function of mucin concentration and pH. Furthermore, we used both reducing (dithiothreitol, DTT) and chaotropic agents (guanidinium chloride and urea) to probe the mesoscopic forces that mediate the integrity of the polymer network. At neutral pH both gastric and duodenal mucins formed self-assembled semi-dilute networks above a certain critical mucin concentration (c*) with the viscosity (η) scaling as η∼c(0.53±0.08) for MUC5AC and η∼c(0.53±0.06) for MUC2, where c is the mucin concentration. Above an even higher mucin concentration threshold (ce , the entanglement concentration) reptation occurs and there is a dramatic increase in the viscosity scaling, η∼c(3.92±0.38) for MUC5AC and η∼c(5.1±0.8) for MUC2. The dynamics of the self-assembled comb polymers is examined in terms of a scaling model for flexible polyelectrolyte combs. Both duodenum and gastric mucin are found to be pH switchable gels, gelation occurring at low pHs. There is a hundred-fold increase in the elastic shear modulus once the pH is decreased. The addition of DTT, guanidinium chloride and urea disassembles both the semi-dilute and gel structures causing a large increase in the compliance (decrease in their shear moduli). Addition of the polyphenol EGCG has a reverse effect on mucin viscoelasticity, that is, it triggers a sol-gel transition in semi-dilute mucin solutions at neutral pH.

  20. [Carcinoma of the pancreas at the site of an intraductal papillary mucinous neoplasia].

    PubMed

    Fieger, A J; Demmel, N; Mündel, D F-X; Schenck, R M; Harnisch, T; Nüssler, N C

    2009-04-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are intraductally located, mucin-producing cystic neoplasms of the pancreas with a malignant potential. We report about a 54-year-old female who underwent segmental resection of the pancreas for non-invasive IPMN. The surgical margins were tumour-negative. Three years later a highly suspicious tumour of the pancreatic tail was detected during routine follow-up. Resection of the pancreatic tail was performed. The histological analysis revealed an adenocarcinoma. This case suggests the development of a pancreatic carcinoma from a non-invasive IPMN and raises the question about the extent of surgery of non-invasive IPMNs of the pancreas.

  1. Dual Roles of Gastric Gland Mucin-specific O-glycans in Prevention of Gastric Cancer

    PubMed Central

    Nakayama, Jun

    2014-01-01

    Gastric gland mucin is secreted from gland mucous cells, including pyloric gland cells and mucous neck cells located in the lower layer of the gastric mucosa. These mucins typically contain O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc) attached to the scaffold protein MUC6, and biosynthesis of the O-glycans is catalyzed by the glycosyltransferase, α1,4-N-acetylglucosaminyltransferase (α4GnT). We previously used expression cloning to isolate cDNA encoding α4GnT, and then demonstrated that αGlcNAc functions as natural antibiotic against Helicobacter pylori, a microbe causing various gastric diseases including gastric cancer. More recently, it was shown that αGlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma. This review summarizes these findings and identifies dual roles for αGlcNAc in gastric cancer. PMID:24761044

  2. A Rare Case of an Adult with Untreated Bladder Exstrophy Presenting with Signet-Ring Cell Adenocarcinoma of Urinary Bladder

    PubMed Central

    Kumar, Vikash; Kasat, Gaurav; Sawant, Ajit

    2016-01-01

    Untreated bladder exstrophy in an adult is rare, as the defect is obvious and primary reconstruction is usually done in infancy. There are less than 90 reported cases of primary adenocarcinoma in an untreated bladder exstrophy in literature and only two such case reports from India. Of these, only one case was of signet-ring cell type of mucinous adenocarcinoma. Here we report the second case of signet-ring cell adenocarcinoma in a 63 year old male with untreated bladder exstrophy (oldest patient in literature), to highlight the extreme rarity, yet distinct possibility and challenges faced in surgical management of such cases. PMID:28050437

  3. Secondary mucinous carcinoma of the skin.

    PubMed

    Frances, Laura; Cuesta, Laura; Leiva-Salinas, Maria; Bañuls, Jose

    2014-04-16

    We report a case of a woman who presented with a cystic-appearing nodule on her left nipple. After cutaneous biopsy and gynecological staging study, she was diagnosed with skin invasion of mucinous carcinoma of the breast. We describe the main features of this rare tumor and the controversies in its diagnosis because primary and metastatic mucinous carcinomas in skin are histologically indistinguishable.

  4. Mucinous micropapillary carcinoma of the breast: an aggressive counterpart to conventional pure mucinous tumors.

    PubMed

    Barbashina, Violetta; Corben, Adriana D; Akram, Muzaffar; Vallejo, Christina; Tan, Lee K

    2013-08-01

    Mucinous micropapillary carcinoma of the breast, also described as "pure mucinous carcinoma with micropapillary pattern," has recently come to attention as an unusual form of invasive breast cancer exhibiting dual mucinous and micropapillary differentiation. Despite increasing awareness of this morphologic variant, its clinical significance has not yet been elucidated. Here, we present 15 additional examples of these rare tumors to highlight some important differences between mucinous micropapillary carcinoma of the breast and ordinary pure mucinous carcinomas. The key features of mucinous micropapillary carcinoma of the breast included (a) largely or entirely mucinous appearance (>90% mucinous morphology), (b) distinctive micropapillary arrangement of the neoplastic cells, (c) intermediate to high nuclear grade, (d) "hobnail" cells, and (e) frequent psammomatous calcifications. In contrast to ordinary pure mucinous carcinomas, 20% of mucinous micropapillary carcinomas of the breast were characterized by human epidermal growth factor receptor 2 positivity, and 23% were p53 positive. More than half of mucinous micropapillary carcinomas of the breast (60%) demonstrated lymphovascular invasion, sometimes extensive. Synchronous axillary lymph node metastases were detected in 33% of patients and, on 2 occasions, involved more than 10 nodes. With a median follow-up of 4.5 years, we identified 1 patient (7%) with chest wall recurrence of mucinous micropapillary carcinoma of the breast after mastectomy. We conclude that mucinous micropapillary carcinomas of the breast constitute a clinically aggressive subset of mucin-producing breast carcinomas characterized by an increased capacity for lymphatic invasion and regional lymph node metastasis, reflective of their dual phenotype. Recognition of the morphologic and biologic heterogeneity within breast cancer subtypes should allow for a more accurate classification of the individual tumors and better patient stratification for

  5. Management of primary adenocarcinoma of the female urethra: Report of two cases and review of the literature.

    PubMed

    Wang, Xinjun; Bai, Peiming; Su, Hanzhong; Luo, Guangcheng; Zhong, Zhaohui; Zhao, Xiaokun

    2012-11-01

    Primary adenocarcinoma of the female urethra is rare and only a few retrospective cases have been published. The origin of urethral adenocarcinomas remains unclear. Certain authors have suggested that urethral adenocarcinomas in females originate at the periurethral Skene's glands. We report one case of urethral adenocarcinoma of the proximal urethra in a 44-year-old female who presented with painless urethral bleeding. Abdominal and pelvic CT scan with contrast and chest radiology were unremarkable. Biopsy of the mass revealed adenocarcinoma of the urethra. The patient was treated with partial urethrectomy and was free of disease for more than 5 years. We also present another rare case of mucinous adenocarcinoma in a 52-year-old female who complained of an enlarged urethral mass. Pelvic MRI revealed a tumor surrounding the whole urethra and bilateral inguinal lymph nodes. A puncture biopsy later revealed that the tumor was mucinous adenocarcinoma. Anterior pelvic exenteration with pelvic and bilateral lymph node dissection was performed and chemotherapy was administered. The patient was followed up for 12 months and did not experience local recurrence or distant metastasis. In conclusion, for the diagnosis of urethral cancer, a biopsy is necessary for any suspicious urethral lesions. MRI is recommended for tumor staging. Small, superficial, distal urethral tumors may be treated with excision of the distal urethra. For advanced female urethral cancer, a combination of chemotherapy, radiation therapy and surgery is recommended for optimal local and distant disease control. Regular follow-up is required in these patients.

  6. Mucinous eccrine nevus: a case report and literature review.

    PubMed

    Chen, Jia; Sun, Jian-fang; Zeng, Xue-si; Liu, Yi; Jiang, Yi-qun; Li, A-mei; Song, Ya-li

    2009-06-01

    Mucinous eccrine nevus (MEN) is a rare variant of eccrine nevus, characterized by a proliferation of normal eccrine structure surrounded by mucin deposits. We report herein the eighth case of mucinous eccrine nevus in the literature, with abundant mucin deposits not only in the stroma surrounding the eccrine glands but also in the superficial dermis. The literature is reviewed.

  7. Regulation of Airway Mucin Gene Expression

    PubMed Central

    Thai, Philip; Loukoianov, Artem; Wachi, Shinichiro; Wu, Reen

    2015-01-01

    Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes. PMID:17961085

  8. Biomimetic oral mucin from polymer micelle networks

    NASA Astrophysics Data System (ADS)

    Authimoolam, Sundar Prasanth

    Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated using affinity-based interactions on synthetic and biological surfaces. Unlike conventional polyelectrolyte-based LBL methods, pre-assembled biotin-functionalized filamentous (worm-like) micelles was utilized as the network building block, which from complementary additions of streptavidin generated synthetic networks of desired thickness. The biomimetic nature in those synthetic networks are studied by evaluating its structural and bio-functional properties. Structurally, synthetic networks formed a nanoporous mesh. The networks demonstrated excellent surface hydration property and were able capable of microbial capture. Those functional properties are akin to that of natural mucin networks. Further, the role of synthetic mucin as a drug delivery vehicle, capable of providing localized and tunable release was demonstrated. By incorporating antibacterial curcumin drug loading within synthetic networks, bacterial growth inhibition was also demonstrated. Thus, such bioactive interfaces can serve as a model for independently characterizing mucin network properties and through its role as a drug carrier vehicle it presents exciting future opportunities for localized drug delivery, in regenerative applications and as bio

  9. Formulation and in vitro release studies of pegylated mucin based matrix tablets.

    PubMed

    Eraga, Sylvester Okhuelegbe; Arhewoh, Matthew Ikhuoria; Iwuagwu, Magnus Amara; Ukponahiusi, Oyenmwen Enoma

    2015-01-01

    The effects of polymer concentration on the flow properties of granules and in-vitro release profiles from matrix tablets of three model drugs formulated from pegylated mucin base was investigated. Mucin was extracted from the African giant snail and in combination with PEG was used to produce a copolymer matrix base, which was mixed with the model drugs using wet granulation method. The granules and tablets were evaluated according to official and unofficial requirements. Results showed best flow with Acetylsalicylic acid (ASA) and Chloroquine Phosphate (CQ) granules with Hausner ratio of 1.04-1.2, Carr's index of 4.2-17.5% and angle of repose between 19°-26°. The tablets met B.P specifications with respect to tablet weights, friability and drug content. The release profiles showed faster release of the drug with high content of PEG and a slower release with high concentration of mucin. Pegylated mucin base will find useful application in the development of a wide range of formulations.

  10. Sialomucins are characteristically O-acylated in poorly differentiated and colloid prostatic adenocarcinomas.

    PubMed

    Sáez, C; Japón, M A; Conde, A F; Poveda, M A; Luna-Moré, S; Segura, D I

    1998-12-01

    Mucinous glycoproteins are secreted by prostatic adenocarcinomas and might play important roles in tumor invasion and metastasis. Their histochemical properties on routine biopsy specimens have not been fully characterized. We present a histochemical study of mucin in 21 prostatic adenocarcinomas, with particular focus on the demonstration of different types of sialomucins. We applied the following histochemical techniques to routinely processed, formalin-fixed, paraffin-embedded tissue sections: Alcian blue (pH 2.5) and periodic acid-Schiff to reveal both acidic and neutral mucins; high iron diamine and Alcian blue (pH 2.5) to show sulfated and acidic nonsulfated mucosubstances simultaneously; periodic acid borohydride, potassium hydroxide, and periodic acid-Schiff to demonstrate O-acylated sialic acids; periodic acid thionine-Schiff, potassium hydroxide, and periodic acid-Schiff to differentiate pre-existing glycols from those revealed after saponification procedures; and periodic acid borohydride and periodic acid-Schiff to show C9-O-acylated sialic acid. These techniques are useful tools for demonstrating neutral and acidic (sialo- and sulfo-) mucins and di(C8,C9- or C7,C9-)-O-acylated, tri(C7,C8,C9-)-O-acylated and mono(C9)-O-acylated sialomucins. Most prostatic adenocarcinomas showed acidic mucins, with sialomucins predominating over sulfomucins. Well-differentiated and moderately differentiated noncolloid tumors had non-O-acylated sialomucins. Poorly differentiated tumors contained mono-O-acylated (C9) sialomucins, and colloid-type tumors secreted mono-, di-, and tri-O-acylated sialoglycoproteins. Acidic mucins, mainly sialomucins, constitute the major secretory component in prostatic adenocarcinomas, and our results show that the O-acylation of these sialoglycoproteins inversely correlates with tumor differentiation. Well-differentiated and moderately differentiated tumors are not O-acylated, whereas the poorly differentiated ones characteristically have O

  11. Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma.

    PubMed

    Kim, Sung Eun; Park, Ji Hye; Hong, Soonwon; Koo, Ja Seung; Jeong, Joon; Jung, Woo-Hee

    2012-12-01

    Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.

  12. Lung adenocarcinoma: Sustained subtyping with immunohistochemistry and EGFR, HER2 and KRAS mutational status.

    PubMed

    Sousa, Vitor; Rodrigues, Carolina; Silva, Maria; Alarcão, Ana Maria; Carvalho, Lina

    2015-01-01

    Pulmonary adenocarcinomas are still in the process of achieving morphological, immunohistochemical and genetic standardization. The ATS/ERS/IASLC proposed classification for lung adenocarcinomas supports the value of the identification of histological patterns, specifically in biopsies. Thirty pulmonary adenocarcinomas were subjected to immunohistochemical study (CK7, CK5, 6, 18, CK20, TTF1, CD56, HER2, EGFR and Ki-67), FISH and PCR followed by sequencing and fragment analysis for EGFR, HER2 and KRAS. Solid pattern showed lower TTF1 and higher Ki-67 expression. TTF1 expression was higher in non-mucinous lepidic and micropapillary patterns when compared to acinar and solid and acinar, solid and mucinous respectively. Higher Ki67 expression was present in lepidic and solid patterns compared to mucinous. EGFR membranous staining had increasing expression from non-mucinous lepidic/BA pattern to solid pattern and micropapillary until acinar pattern. EGFR mutations, mainly in exon 19, were more frequent in females, together with non-smoking status, while KRAS exon 2 mutations were statistically more frequent in males, especially in solid pattern. FISH EGFR copy was correlated gross, with mutations. HER2 copy number was raised in female tumours without mutations, in all cases. Although EGFR and KRAS mutations are generally considered mutually exclusive, in rare cases they can coexist as it happened in one of this series, and was represented in acinar pattern with rates of 42.9% and 17.9%, respectively. EGFR mutations were more frequent in lepidic/BA and acinar patterns. Some cases showed different EGFR mutations. The differences identified between the adenocarcinoma patterns reinforce the need to carefully identify the patterns present, with implications in diagnosis and in pathogenic understanding. EGFR and KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the

  13. Small Bowel Adenocarcinoma.

    PubMed

    Aparicio, Thomas; Zaanan, Aziz; Mary, Florence; Afchain, Pauline; Manfredi, Sylvain; Evans, Thomas Ronald Jeffry

    2016-09-01

    Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.

  14. Prostate Ductal Adenocarcinoma.

    PubMed

    Amin, Ali

    2017-03-30

    Prostate ductal adenocarcinoma (PDA) is a rare subtype of prostate adenocarcinoma that shows more aggressive behavior than conventional prostatic acinar adenocarcinoma. PDA demonstrates similar clinical and paraclinical features such as prostatic acinar adenocarcinoma; therefore, clinical distinction of the 2 entities is very difficult (if not impossible) and histopathology plays an important role in the diagnosis of the disease. This review discusses all the necessary information needed for the diagnosis and prognosis of PDA including the morphologic features of PDA, an introduction about the known variants of PDA with helpful hints in grading of each variant, tips on differential diagnosis of PDA from the common morphologic mimickers, a detailed discussion on the value of immunohistochemistry in the diagnosis of PDA, and pathologic features that are helpful in determining the outcome.

  15. Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment.

    PubMed

    Grützmann, Robert; Niedergethmann, Marco; Pilarsky, Christian; Klöppel, Günter; Saeger, Hans D

    2010-01-01

    Pancreatic intraductal papillary mucinous neoplasms (IPMNs) rank among the most common cystic tumors of the pancreas. For a long time they were misdiagnosed as mucinous cystadenocarcinoma, ductal adenocarcinoma in situ, or chronic pancreatitis. Only in recent years have IPMNs been fully recognized as clinical and pathological entities, although their origin and molecular pathogenesis remain poorly understood. IPMNs are precursors of invasive carcinomas. When resected in a preinvasive state patient prognosis is excellent, and even when they are already invasive, patient prognosis is more favorable than with ductal adenocarcinomas. Subdivision into macroscopic and microscopic subtypes facilitates further patient risk stratification and directly impacts treatment. There are main duct and branch duct IPMNs, with the main duct type including the intestinal, pancreatobiliary, and oncocytic types and the branch duct type solely harboring the gastric type. Whereas main duct IPMNs have a high risk for malignant progression, demanding their resection, branch duct IPMNs have a much lower risk for harboring malignancy. Patients with small branch duct/gastric-type IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic surveillance.

  16. Physical Properties of the Glycoprotein Mucin

    NASA Astrophysics Data System (ADS)

    Matthews, Garrett; Davis, William; Superfine, Richard; Boucher, Richard

    2003-03-01

    Epithelial cell surfaces are covered by a protective gel known as mucus. The physiological function of this gel depends on its rheological properties, and these properties are largely derived from the secreted glycoprotein mucin. The genetic disease Cystic Fibrosis (CF) is characterized by the adhesion of thick, viscous mucus on these tissues. In the lungs, this results in the interruption of mucus transport thus compromising the first line of defense against pathogens in these tissues. In order to restore the flow of tracheobronchial mucus out of the body, knowledge of the molecular and physical properties of mucin and mucin solutions would be greatly beneficial. The present model for these molecules is that of a long linear strand consisting of highly glycosylated regions linked by cystein-rich globular regions. It is thought that the globular regions may interact either through intermolecular disulfide bonds or through hydrophobic interactions. It has also been speculated that the glycosylated regions may have lectin-like interactions. In the present work, single mucin molecules were imaged at high resolution using atomic force microscopy (AFM). Phase mode imaging was used to map the interactions between functionalized AFM tips and the molecular topography. Additionally, using force-distance curves with the AFM, the adhesion between mucin bound tips and cell surface glycocalyx and glycocalyx-like model surfaces, was measured. And, finally, the viscoelastic properties of mucin solutions were measured using the recently developed technique, single particle tracking microrheology. A model is being developed that will incorporate the properties of mucins beginning at the single molecule and ending with the bulk viscoelastic properties.

  17. Immunophenotype and human papillomavirus status of serous adenocarcinoma of the uterine cervix.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Kasamatsu, Takahiro; Oda-Otomo, Rie; Okada, Satoshi; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Tsuda, Hitoshi

    2015-04-01

    Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.

  18. Secretory myoepithelial carcinoma: a histologic and molecular survey and a proposed nomenclature for mucin producing signet ring tumors.

    PubMed

    Bastaki, Jassem M; Purgina, Bibianna M; Dacic, Sanja; Seethala, Raja R

    2014-01-01

    Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38 months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as 'secretory myoepithelial carcinoma.' They behave in a fairly indolent fashion and do not share the major molecular alterations seen

  19. Primary vaginal adenocarcinoma of intestinal type arising from an adenoma: case report and review of the literature.

    PubMed

    Mudhar, H S; Smith, J H; Tidy, J

    2001-04-01

    A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year-old woman with no history of diethylstilbestrol exposure that on microscopic examination was a moderately differentiated adenocarcinoma of intestinal type. The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated sialomucin, a specific marker of large intestinal differentiation. The initial interpretation favored a metastasis from a colonic adenocarcinoma, but clinical investigations showed no evidence of a primary gastrointestinal lesion. The morphology, histochemical, and differential cytokeratin profile led to the lesion being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina arising from a tubular adenoma. Although a very rare tumor, awareness of this lesion is important as it must be distinguished from metastatic adenocarcinomas from other sites.

  20. In vitro utilization of mucin by Bacteroides fragilis.

    PubMed Central

    Roberton, A M; Stanley, R A

    1982-01-01

    A method for isolating pig colon mucin in a soluble high-molecular-weight form, suitable for addition to bacterial growth media, is described. This preparation was utilized as a sole carbohydrate energy source by two strains of Bacteroides fragilis. The extent of degradation was compared with that of commercial pig gastric mucin by the same strains. Gas-liquid chromatographic analysis of the mucin carbohydrates and gel chromatography of the preparations were carried out before and after in vitro degradation. The mucin carbohydrates were utilized only to a very limited extent, colon mucin being more resistant to degradation than gastric mucin. Both mucins chromatographed at or near the excluded volume on Sepharose 4B, and only in the case of ATCC 25285 grown on gastric mucin was a significant degradation peak detected. If mucins are degraded in vivo by the sequential action of several bacteria, a pure culture in vitro might be expected to degrade mucins to a limited extent only. Techniques previously used to examine mucin utilization by pure cultures may have overlooked limited mucin degradation demonstrated by the methods used in this work. PMID:6174077

  1. Mucinous carcinoma occurring in the male breast.

    PubMed

    Ishida, Mitsuaki; Umeda, Tomoko; Kawai, Yuki; Mori, Tsuyoshi; Kubota, Yoshihiro; Abe, Hajime; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Tani, Tohru; Okabe, Hidetoshi

    2014-02-01

    Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.

  2. Adenocarcinoma of the thymus, enteric type: report of 2 cases, and proposal for a novel subtype of thymic carcinoma.

    PubMed

    Moser, Bernhard; Schiefer, Ana Iris; Janik, Stefan; Marx, Alexander; Prosch, Helmut; Pohl, Wolfgang; Neudert, Barbara; Scharrer, Anke; Klepetko, Walter; Müllauer, Leonhard

    2015-04-01

    We report 2 cases of primary thymic adenocarcinoma with enteric differentiation. One carcinoma occurred in a 41-year-old man as a 7-cm-diameter cystic tumor and the other one in a 39-year-old woman as a 6-cm-diameter solid mass. Both tumors were located in the anterior mediastinum. Clinical staging did not reveal any extrathymic tumor. Histologically, the tumors were classified as adenocarcinoma, not otherwise specified, and a mucinous (colloid) carcinoma, respectively. Immunohistochemically, both tumors were positive for cytokeratin 20 (CK20), CDX2, and carcinoembryonic antigen, reflecting enteric differentiation. A review of the literature on 43 other cases of primary thymic adenocarcinomas suggested 11 further cases with enteric differentiation, as assessed by CK20 and/or CDX2 expression. We propose that thymic adenocarcinoma with enteric differentiation represents a novel subtype of thymic carcinoma. It is mostly of mucinous morphology and frequently associated with thymic cysts. The clinical outcome is variable. Recognition of primary thymic adenocarcinoma with enteric differentiation is helpful for the differentiation from metastatic disease, mainly from the gastrointestinal tract.

  3. Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

    PubMed

    Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

    2016-10-01

    CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

  4. Combined adenocarcinoma-carcinoid tumor of transverse colon.

    PubMed

    Bhattacharjee, Prosanta Kumar; Halder, Shyamal

    2013-01-01

    A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the splenic flexure with a part of ileum, approximately three feet proximal to ileo-caecal junction, adherent to it. No significant mesenteric lymph node enlargement was evident. The patient underwent resection of the growth along with the segment of adherent ileum. Continuity was re-established by a colo-colic and ileo-ileal anastomosis respectively. Patient received adjuvant chemotherapy. Post-operative histopathology demonstrated a composite histological pattern with an admixture of carcinoid tumor and adenocarcinoma, invasion of ileal serosa and adenocarcinomatous deposits in mesocolic lymph nodes, the tumor staging being (T4, N0, M0/Stage II) for carcinoid and (T4, N1, M0/Stage III) for adenocarcinoma. Patient was followed-up for a year and was doing well without any evidence of recurrence.

  5. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

    PubMed

    Castrillon, Diego H; Lee, Kenneth R; Nucci, Marisa R

    2002-01-01

    We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

  6. Do clinical and immunohistochemical findings of pure mucinous breast carcinoma differ from mixed mucinous breast carcinoma?

    PubMed

    Erhan, Y; Ciris, M; Zekioglu, O; Erhan, Y; Kapkac, M; Makay, O; Ozdemir, N

    2009-01-01

    Mucinous carcinoma of the breast is a relatively rare histologic type with two subtypes: pure and mixed. It has a favourable prognosis with a low risk of axillary metastases. The prognosis for pure mucinous carcinoma (PMC) was much better than for the mixed mucinous carcinoma (MMC). The aim of the study is to determine suitable candidates for breast or axillary conservation in mucinous carcinoma subtypes. The slides of 26 pure and 23 mixed mucinous carcinomas of the breast were evaluated. The clinical, pathological and immunohistochemical features between PMCs and MMCs were compared. MMC displayed greater metastatic potential (p < 0.05), p53 positivity (p < 0.05) and c-erbB-2 positivity (p <0.001) than PMCs. PMCs smaller than 2 cm had less metastatic capacity and extranodal invasion compared to MMCs smaller than 2 cm (p < 0.001 and p < 0.01, respectively). MMCs smaller than 2 cm displayed weaker ER positivity but greater c-erbB-2 positivity than PMCs smaller than 2 cm (p < 0.01). In conclusion, MMC had worse prognostic factors than PMC with both types of mucinous carcinoma showing similar ER and PR positive status. Even if PMCs and especially smaller PMCs display more favourable prognostic features, including less axillary lymph node involvement, it is appropriate to use sentinel lymph node biopsy to make better axillary assessment.

  7. [Giant appendiceal mucocele during laparotomy for acute abdomen. Report of a case and brief review].

    PubMed

    Caiazzo, P; Comentale, A; Rampone, B; Di Lascio, P; Morlino, A; Pastore, M; Del Vecchio, G; Tramutoli, P R

    2010-01-01

    The authors describe a case of giant appendiceal mucocele, secondary to a mucinous neoplasm of the appendix, diagnosed during laparotomy for acute abdomen. By a review of the literature they stress the rarity of this lesion, the particular onset in their case as acute complication of appendiceal neoplasm with rupture of the intestinal wall, the difficulties of diagnosis and management in emergency.

  8. Quantitative microscopic evaluation of mucin areas and its percentage in mucinous carcinoma of the breast using tissue histological images.

    PubMed

    Saha, Monjoy; Arun, Indu; Basak, Bijan; Agarwal, Sanjit; Ahmed, Rosina; Chatterjee, Sanjoy; Bhargava, Rohit; Chakraborty, Chandan

    2016-06-01

    Mucinous carcinoma (MC) of the breast is very rare (∼1-7% of all breast cancers), invasive ductal carcinoma. Presence of pools of extracellular mucin is one of the most important histological features for MC. This paper aims at developing a quantitative computer-aided methodology for automated identification of mucin areas and its percentage using tissue histological images. The proposed method includes pre-processing (i.e., colour space transformation and colour normalization), mucin regions segmentation, post-processing, and performance evaluation. The proposed algorithm achieved 97.74% segmentation accuracy in comparison to ground truths. In addition, the percentage of mucin present in the tissue regions is calculated by the mucin index (MI) for grading MC (pure, moderately, minimally mucinous).

  9. Anal Canal Adenocarcinoma in a Patient with Longstanding Crohn’s Disease Arising From Rectal Mucosa that Migrated From a Previously Treated Rectovaginal Fistula

    PubMed Central

    Maejima, Taku; Kono, Toru; Orii, Fumika; Maemoto, Atsuo; Furukawa, Shigeru; Liming, Wang; Kasai, Shoji; Fukahori, Susumu; Mukai, Nobutaka; Yoshikawa, Daitaro; Karasaki, Hidenori; Saito, Hiroya; Nagashima, Kazuo

    2016-01-01

    Patient: Female, 50 Final Diagnosis: Anal canal adenocarcinoma Symptoms: — Medication: — Clinical Procedure: CT • MRI • biopsy Specialty: Surgery Objective: Unknown ethiology Background: This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn’s disease (CD). Case Report: A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months’ duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. Conclusions: Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract. PMID:27373845

  10. A Case Report of Male Occult Breast Cancer First Manifesting as Axillary Lymph Node Metastasis With Part of Metastatic Mucinous Carcinoma.

    PubMed

    He, Mengna; Liu, He; Jiang, Yuxin

    2015-06-01

    Occult breast cancer (OBC) is a type of breast cancer without any symptoms in the breast (no primary cancer lesion is found in either breast on a physical examination or imaging examination such as ultrasound and mammography). The incidence of OBC is rare in females, whereas in males, there are few cases of breast cancer, and the rate of OBC is very low. This is the first time report a case of male OBC first manifested as axillary metastasis, of which the pathological results showed moderately differentiated adenocarcinoma with part of metastatic mucinous carcinoma.A 40-year-old male patient presenting palpable masses in his left axillary on physical and imaging examination revealed unremarkable despite of multiple swollen lymph nodes in the left axillary, and the resected sample showed metastatic adenocarcinoma with part of metastatic mucinous carcinoma. Based on immunohistochemical analysis, positive of estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (Her-2), it was identified as an OBC.This is the fourth case report of male OBC in the literature; 1 case was reported in China in 2008, and it was metastatic infiltrating ductal carcinoma, and 2 cases were reported in Korea in 2012, one of which was reported as metastatic carcinoma and the other was metastatic adenocarcinoma; however, our case was a moderately differentiated adenocarcinoma with part of mucinous carcinoma. Our case of male OBC could metastasize to supraclavicular region and lung in addition to axillary lymph nodes, and the prognosis was relatively poor compared to the 3 cases reported before.The aim of this case report is to introduce the imaging, pathological features, and management of a rare male OBC.

  11. Villoglandular papillary adenocarcinoma: case report

    PubMed Central

    Salek, Ghizlane; Lalya, Issam; Rahali, Driss Moussaoui; Dehayni, Mohamed

    2016-01-01

    Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Herein, we report a case of VPA diagnosed and managed successfully with conservative measure. This management is particularly desirable in young women to preserve reproductive capability. PMID:28293348

  12. Mapping the Protein Domain Structures of the Respiratory Mucins: a mucin proteome coverage study

    PubMed Central

    Cao, Rui; Wang, T. Tiffany; DeMaria, Genevieve; Sheehan, John K.; Kesimer, Mehmet

    2012-01-01

    Mucin genes encode a family of the largest expressed proteins in the human genome. The proteins are highly substituted with O-linked oligosaccharides which greatly restrict access to the peptide backbones. The genomic organization of the N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been established and is available in the sequence databases. However, much less is known about the fate of their exposed protein regions after translation and secretion, and, to date, detailed proteomic studies complementary to the genomic studies are rather limited. Using mucins isolated from cultured human airway epithelial cell secretions, trypsin digestion and mass spectrometry, we investigated the proteome coverage of the mucins responsible for the maintenance and protection of the airway epithelia. Excluding the heavily glycosylated mucin domains, up to 85% coverage of the N-terminal region of the gel forming mucins MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were covered, suggesting that more N- and sparsely O-glycosylated regions as well as possible other modifications are available at the C-terminus. All possible peptides from the cysteine-rich regions that interrupt the heavily glycosylated mucin domains were identified. Interestingly, 43 cleavage sites from ten different domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic cleavage site on the N-terminal end of the peptide, indicating potential exposure to proteolytic and/or “spontaneous cleavages”. Some of these non-tryptic cleavages may be important for proper maturation of the molecule, before and/or after secretion. Most of the peptides identified from MUC16 were from the SEA region. Surprisingly, three peptides were clearly identified from its heavily glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven different domains of the molecule. All peptides from the MUC1 cytoplasmic domain were detected along with the

  13. Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer.

    PubMed

    Mukherjee, Pinku; Madsen, Cathy S; Ginardi, Amelia R; Tinder, Teresa L; Jacobs, Fred; Parker, Joanne; Agrawal, Babita; Longenecker, B Michael; Gendler, Sandra J

    2003-01-01

    Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.

  14. Membrane-bound mucin modular domains: from structure to function.

    PubMed

    Jonckheere, Nicolas; Skrypek, Nicolas; Frénois, Frédéric; Van Seuningen, Isabelle

    2013-06-01

    Mucins belong to a heterogeneous family of large O-glycoproteins composed of a long peptidic chain called apomucin on which are linked hundreds of oligosaccharidic chains. Among mucins, membrane-bound mucins are modular proteins and have a structural organization usually containing Pro/Thr/Ser-rich O-glycosylated domains (PTS), EGF-like and SEA domains. Via these modular domains, the membrane-bound mucins participate in cell signalling and cell interaction with their environment in normal and pathological conditions. Moreover, the recent knowledge of these domains and their biological activities led to the development of new therapeutic approaches involving mucins. In this review, we show 3D structures of EGF and SEA domains. We also describe the functional features of the evolutionary conserved domains of membrane-bound mucins and discuss consequences of splice events.

  15. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Pereira, Daniela; Pinto, Rita; Almeida, Raquel; Söderberg, Ola; Mandel, Ulla; Clausen, Henrik; Felix, Ana; Lunet, Nuno; David, Leonor

    2015-02-01

    The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.

  16. [Mucinous papillary cystadenoma of the pancreas].

    PubMed

    Ledezma, G; Salloum, S; de Sulbarán, Y; de Armas, L

    1992-01-01

    The case of a 15-years-old female patient is presented, who referred pain and presence of a mass in the left upper quadrant of the abdomen. Diagnostic imaging showed a 9 cm diameter cystic lesion in the tail of the pancreas which was removed surgically. Histology demonstrated a pancreatic mucinous cystadenoma with borderline biological behaviour. A review of the literature related to cystic neoplasms of the pancreas is realized.

  17. Viscous fingering of HCI through gastric mucin

    NASA Astrophysics Data System (ADS)

    Bhaskar, K. Ramakrishnan; Garik, Peter; Turner, Bradley S.; Bradley, James Douglas; Bansil, Rama; Stanley, H. Eugene; Lamont, J. Thomas

    1992-12-01

    THE HCI in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium1-4 and acts as a diffusion barrier5,6 Bicarbonate ions secreted by the gastric epithelium7 are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface8-10. How does HCI, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCI through solutions of pig gastric mucin produces viscous fingering patterns11-18 dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCI neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCI secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HC1 in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.

  18. [A case of multiple breast mucinous carcinomas].

    PubMed

    Maeda, Tetsuyo; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2010-11-01

    A case was a 46-year-old woman who presented with the left breast lump confirmed about 30 years ago. In August 2006, the patient came to our hospital for consultation due to her breast lump was enlarged. Mammography revealed a frequent occurrence of the mass shadow of marginal irregularity and we diagnosed it with category 4. Breast echography showed a lot of irregular lesions. Even breast MRI presented a multiple mass-related lesion. The malignancy was possible, and a needle biopsy diagnosed them to be mucinous carcinoma. Pectoralis muscle preservation mastectomy and sentinel lymph node biopsy technique were used for surgery. Histopathology also diagnosed it to be mucinous carcinoma, T2N0 M0, stage IIA, ER (+), PgR (+), HER2 score 0. It has been 4 years since the operation but no sign of recurrence/metastasis was observed at present. There have been few reports of breast cancer with multiple cases, mucinous carcinoma as a case in point. Therefore, we report the invaluable case in addition to some paper consideration with it.

  19. Mucins in contact lens wear and dry eye conditions.

    PubMed

    Ramamoorthy, Padmapriya; Nichols, Jason J

    2008-08-01

    Ocular mucins are thought to play integral roles in ocular surface lubrication, anchoring of the aqueous, stabilizing the lipid components of the tear film, eliminating foreign bodies and pathogens, and with potential involvement in cell cycle mediation and apoptotic activity of ocular surface epithelia. Ocular mucins are of secreted and membrane-associated types. Secreted mucins may be of large gel-forming type or small soluble mucins (e.g., MUC5AC and MUC7). Membrane-associated mucins such as MUCs 1 and 4 are a major component of the glycocalyx. They are thought to render structural support to the microplicae and mediate epithelial cell cycle and apoptotic activity. The alterations in ocular mucins with contact lens wear are unclear. Recent work shows mucin expression may be up-regulated during the early years of contact lens wear, and with long-term lens wear, mucin expression may return to normal levels or sub-normal levels, although this is not well understood. Further, the polar nature of mucins may be associated with their affinity for contact lens surfaces making them a component of contact lens deposition. This has potential implications in the wettability and tolerability of contact lenses, and may be impacted by surface coatings, polymer characteristics, or care solutions. Conjunctival mucin gene expression and secretion may be deficient in several ocular surface disorders associated with dry eye. Deficiency and alterations in glycosylation characteristics of MUC5AC and MUC2 have been reported in both Sjögren and non-Sjögren dry eye types. Decreased binding of the membrane-associated mucin MUC16 to the conjunctival epithelium has been reported in Sjögren dry eye while MUC1 alterations have been reported in Sjögren and non-Sjögren dry eye states. In view of the mucin involvement in dry eye conditions, stimulation of mucus secretion pathways may hold promise in the pharmaceutical treatment of dry eye.

  20. The different morphologies of urachal adenocarcinoma do not discriminate genomically by micro-RNA expression profiling.

    PubMed

    Bissonnette, Mei Lin Z; Kocherginsky, Masha; Tretiakova, Maria; Jimenez, Rafael E; Barkan, Güliz A; Mehta, Vikas; Sirintrapun, Sahussapont Joseph; Steinberg, Gary D; White, Kevin P; Stricker, Thomas; Paner, Gladell P

    2013-08-01

    Urachal adenocarcinoma has several morphologic presentations that include mucinous, enteric, signet ring cell, and not otherwise specified. Mixtures of these morphologies can occur, and percentage cut-offs are used for classification. The clinical significance of these morphologic types is currently unknown, and genetic analysis that could elucidate possible intertumoral differences has not been performed. In this study, we analyzed the micro-RNA expression profiles of 12 urachal adenocarcinomas classified using strict morphologic criteria (3 pure enteric, 3 pure mucinous, 2 signet ring cell [both 90% signet ring cell], 2 pure not otherwise specified, and 2 mixed cell types). Of 598 unique human micro-RNAs, 333 were expressed in more than 50% of the samples. Hierarchal clustering showed no distinct patterns in the genetic profiles of the morphologic types. However, there were individual micro-RNA differences when the different types were compared individually or grouped together, either by intracellular mucin production or by grouping enteric and signet ring cell together. In the later group, 13 messenger RNA species were differentially expressed (adjusted P value of ≤.05). However, these micro-RNA differences were small, suggesting more biologic similarity than differences among these entities. Thus, this study suggests that the different morphological subtypes may represent patterns of differentiation or a continuum of a single biological tumor type rather than several distinct types that arose from the urachal remnant epithelium. This finding, if further validated in larger studies, may have implications in future clinical therapeutic trials for urachal adenocarcinoma with regard to patient grouping and choice of therapy.

  1. [Intraductal papillary mucinous tumor: diagnostic and therapeutic approach].

    PubMed

    Seijo Ríos, Susana; Lariño Noia, José; Iglesias García, Julio; Lozano León, Antonio; Domínguez Muñoz, Juan Enrique

    2008-02-01

    Primary cystic pancreatic neoplasms are rare tumors, with an approximate prevalence of 10% of cystic pancreatic lesions. Most of these lesions correspond to mucinous cystic neoplasm, serous cystoadenoma and intraductal papillary mucinous tumor (IPMT). IPMT is characterized by diffuse dilatation of the main pancreatic duct and/or side branches with inner defects related to mucin or tumor, or mucin extrusion from a patent ampulla. IPMT has a low potential for malignancy, with a low growth rate, a low rate of metastatic spread and postsurgical recurrence. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this tumor.

  2. Interaction of Eimeria tenella with intestinal mucin in vitro.

    PubMed

    Tierney, J B; Matthews, E; Carrington, S D; Mulcahy, G

    2007-06-01

    The mucus gel layer overlying the gastrointestinal epithelium plays an important role in host-pathogen interactions. The initial interaction between the coccidian parasite Eimeria tenella and host cells of the intestinal epithelium must occur across this mucus interface. In this study, we examined the relationship between E. tenella and avian mucin, in particular the effect of purified intestinal regional mucin on parasite adherence and invasion in vitro. Secreted mucin from the chicken duodenum and cecum was purified by density gradient centrifugation and gel chromatography. Parasite invasion studies were performed in the Madin-Darby bovine kidney cell model. Eimeria tenella adherence to chicken duodenal mucin was detected, whereas adherence to cecal or bovine mucin was not shown. Parasite invasion into epithelial cells was not influenced by bovine mucin, whereas chicken mucin purified from the duodenum and cecum significantly inhibited invasion. Inhibition of E. tenella invasion into cells by mucin from the duodenum was marginally greater than that of the cecum, but this was not significant. This study demonstrated E. tenella interaction with native chicken intestinal mucin, which in turn inhibited parasite invasion into epithelial cells in vitro.

  3. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

    PubMed Central

    Travis, William D.; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G.; Geisinger, Kim R.; Yatabe, Yasushi; Beer, David G.; Powell, Charles A.; Riely, Gregory J.; Van Schil, Paul E.; Garg, Kavita; Austin, John H. M.; Asamura, Hisao; Rusch, Valerie W.; Hirsch, Fred R.; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M.; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A.; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

    2015-01-01

    , will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated

  4. [Strategies for screening for pancreatic adenocarcinoma in high-risk patients: the place of endoscopic ultrasound].

    PubMed

    Béchade, Dominique

    2011-03-01

    Screening high-risk individuals with imaging tests, such endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention results in decreased pancreatic cancer incidence and mortality in high-risk individuals.

  5. Wheatgrass Extract Ameliorates Hypoxia-induced Mucin Gene Expression in A549 cells

    PubMed Central

    Sim, Ju hwan; Choi, Moon-Hee; Shin, Hyun-Jae; Lee, Ji-Eun

    2017-01-01

    Background: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. Objective: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. Materials and Methods: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared. The mRNA expression level of mucin gene (MUC), 5A, 5B, 8, GM-CSF, TNF-α, and VEGF were evaluated by using real-time polymerase chain reaction. The MUC proteins level before and after knocking out the hypoxia-inducible factor (hif)-1α via short interfering (si) RNA transfection were assessed by immunoblot analysis. Accordingly, the involved cell signaling pathway was evaluated by immunoblot analysis. Results: The inflammatory cytokines (GM-CSF, TNF- α) and the expressions of MUC 5A, 5B, and 8 were augmented by hypoxia. The augmented MUC expression was decreased by the wheatgrass extract administration. Hif-1α gene expression after hypoxia exposure was decreased by wheatgrass. Knockdown of hif-1α by siRNA reduced the mucin gene expression and which was more enhanced by wheatgrass extract. Conclusion: Theses results suggest that wheatgrass may be useful in the treatment of sinonasal disease by inhibiting mucus hypersecretion in airway epithelium. SUMMARY Wheatgrass extract decreases the hypoxia-induced MUC 5A, 5B and 8 expression.Hif-1α gene expression after hypoxia exposure was decreased by wheatgrass.Wheatgrass inhibits p44/42 phosphorylation in hypoxia-exposed airway epithelial cells. Abbreviations used: A549: human lung adenocarcinoma cells, GM-CSF: granulocyte-macrophage colony stimulating factor, HIF: hypoxia inducible factor, IL: interleukin, MUC: mucin, MTT: 3

  6. Anal Canal Adenocarcinoma in a Patient with Longstanding Crohn's Disease Arising From Rectal Mucosa that Migrated From a Previously Treated Rectovaginal Fistula.

    PubMed

    Maejima, Taku; Kono, Toru; Orii, Fumika; Maemoto, Atsuo; Furukawa, Shigeru; Liming, Wang; Kasai, Shoji; Fukahori, Susumu; Mukai, Nobutaka; Yoshikawa, Daitaro; Karasaki, Hidenori; Saito, Hiroya; Nagashima, Kazuo

    2016-07-04

    BACKGROUND This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn's disease (CD). CASE REPORT A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months' duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. CONCLUSIONS Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract.

  7. Isolated mucinous adrenal metastasis in a breast cancer patient.

    PubMed

    Demirci, Umut; Buyukberber, Suleyman; Cakir, Tansel; Poyraz, Aylar; Baykara, Meltem; Karakus, Esra; Tufan, Gulnihal; Benekli, Mustafa; Coskun, Ugur

    2011-12-01

    Mucinous breast carcinoma (MBC) is a rare histological type of breast cancer and rarely associated with advanced disease. We report a case that had MBC with an isolated adrenal metastasis which was removed by laparoscopic adrenelectomy. This case is unique due to the unexpected metastasis of pure mucinous carcinoma developed after 4 years of hormone therapy.

  8. Heterogeneity and persistence length in human ocular mucins.

    PubMed Central

    Round, A N; Berry, M; McMaster, T J; Stoll, S; Gowers, D; Corfield, A P; Miles, M J

    2002-01-01

    Atomic force microscopy (AFM) has been used to investigate the heterogeneity and flexibility of human ocular mucins and their subunits. We have paid particular attention, in terms of theory and experiment, to the problem of inducing the polymers to assume equilibrium conformations at a surface. Mucins deposited from a buffer containing Ni(2+) ions adopt extended conformations on mica akin to those observed for DNA under similar conditions. The heterogeneity of the intracellular native mucins is evident from a histogram of contour lengths, reflecting, in part, the diversity of mucin gene products expressed. Reduction of the native mucin with dithiothreitol, thereby breaking the S==S bonds between cysteine residues, causes a marked reduction in polymer length. These results reflect the modes of transport and assembly of newly synthesized mucins in vivo. By modifying the worm-like chain model for applicability to two dimensions, we have confirmed that under the conditions employed mucin adsorbs to mica in an equilibrated conformation. The determined persistence length of the native mucin, 36 nm, is consistent with that of an extended, flexible polymer; such characteristics will influence the properties of the gels formed in vivo. PMID:12202389

  9. Does St. John's Wort cause regression in gastrointestinal system adenocarcinomas?

    PubMed

    Karaarslan, Serap; Cokmert, Suna; Cokmez, Atilla

    2015-11-15

    St. John's Wort (SJW) is an old herb which has long been consumed widely for its anti-inflammatory, antiviral, and anti-depressive properties. Here we present a detailed clinical evaluation of three cases (two colon and one duodenal adenocarcinoma) with remarkable and intensive lymphoplasmocytic host reaction, at the basal part of tumor, intensive fibrosis, giant cells, plasma cell increase in lymph nodes and few giant cells in germinal centers in resection specimens. The observation of similar host reaction in those tumors having otherwise usual appearance was interesting. None of the cases received neoadjuvant chemoradiotherapy or additional treatment before surgery but only SJW. These cases are presented to increase the awareness about such cases. Further research is needed to reveal the possible effect of SJW, which has long been consumed for different treatment purposes, on human tumors.

  10. Human carcinoma-associated and salivary mucins detected by anti-bovine submaxillary mucin antibodies.

    PubMed

    Golubović, S J; Bojić-Trbojević, Z T

    2006-01-01

    Polyclonal rabbit anti-bovine submaxillary mucin antibodies, anti-BSM IgG, were analyzed by autoradiography and densitometry (after SDS electrophoresis and blotting), ELISA, and IRMA assays for reactivity against native antigen BSM, deglycosylated and desialylated BSM, and human salivary and carcinoma-associated mucins. Known human tumor marker CA19-9 antigen reacted with rabbit anti-BSM IgG under different conditions, either soluble or immobilized. As soluble antigen, in IRMA it reacted with anti-BSM antibodies used both as a catcher and a tracer, as well as in combination with monoclonal anti-CA19-9 antibodies as a catcher. MUC1 mucin is a carrier of this carbohydrate antigen, CA19-9, or sialyl-Lewis(a), as well as of CA15-3 antigen, a known breast tumor marker. Autoradiography and densitometry demonstrated binding of anti-BSM IgG to intact MUC1 in a sample of commercial standard preparation of CA19-9 antigen. The same method and analysis demonstrated binding of anti-BSM IgG to MUC1 and to smaller antigens of 85-120 kD in samples containing CA15-3 antigen: commercial standard preparation, human breast tissue, and human milk. In a sample of whole human saliva, reactions of both isoforms of MUC7 were detected by autoradiography, as bands of 85 and 115 kD, and densitogram analysis also demonstrated reaction with MUC5B. Chemical modifications performed as periodate oxidation and desialylation of the BSM demonstrated carbohydrate (i.e., sialic acid) epitope sensitivity for anti-BSM IgG. The results presented in this work indicate that polyclonal anti-BSM antibodies are specific for sialylated carbohydrate structure on mucins and could serve as a tool for investigation of human carcinoma-associated and salivary mucins.

  11. Studies on the binding of amylopectin sulfate with gastric mucin.

    PubMed

    Kim, Y S; Bella, A; Whitehead, J S; Isaacs, R; Remer, L

    1975-07-01

    Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH.

  12. Is lobular endocervical glandular hyperplasia a cancerous precursor of minimal deviation adenocarcinoma?: a comparative molecular-genetic and immunohistochemical study.

    PubMed

    Kawauchi, Shigeto; Kusuda, Tomoko; Liu, Xu-Ping; Suehiro, Yutaka; Kaku, Tsunehisa; Mikami, Yoshiki; Takeshita, Morishige; Nakao, Motonao; Chochi, Yasuyo; Sasaki, Kohsuke

    2008-12-01

    Although lobular endocervical glandular hyperplasia (LEGH) was originally described as a distinct hyperplastic glandular lesion of the uterine cervix, recent studies have raised a question that LEGH may be a cancerous precursor of minimal deviation adenocarcinoma (MDA) and other mucinous adenocarcinomas (MACs) of the uterine cervix. In the present study, we studied LEGH, MDA, and MAC by using molecular-genetic and immunohistochemical methods for chromosomal imbalance, microsatellite instability, human papillomavirus (HPV) infection, and gastric pyloric-type mucin secretion to clarify their relationship. Comparative genomic hybridization revealed recurrent chromosomal imbalances, that is, gains of chromosome 3q and a loss of 1p, which were common to MDA and MAC, in 3 of 14 LEGHs analyzed (21%). LEGHs with chromosomal imbalances showed a degree of cellular atypia in the hyperplastic glandular epithelium. Dual-color fluorescence in situ hybridization confirmed a gain of chromosome 3 fragment in these cervical glandular lesions. HPV in situ hybridization revealed that high-risk HPV (types 16 and 18) was positive in over 80% of MACs, but negative in all LEGHs and MDAs examined. Microsatellite instability was rarely detected in these cervical glandular lesions. Our present study results demonstrated a molecular-genetic link between LEGH and cervical mucinous glandular malignancies including MDA and MAC, and are thought to support the hypothesis that a proportion of LEGHs are cancerous precursors of MDA and/or MAC.

  13. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

  14. Tear Film Mucins: Front Line Defenders of the Ocular Surface; Comparison with Airway and Gastrointestinal Tract Mucins

    PubMed Central

    Hodges, Robin R.; Dartt, Darlene A.

    2014-01-01

    The ocular surface including the cornea and conjunctiva and its overlying tear film are the first tissues of the eye to interact with the external environment. The tear film is complex containing multiple layers secreted by different glands and tissues. Each layer contains specific molecules and proteins that not only maintain the health of the cells on the ocular surface by providing nourishment and removal of waste products but also protect these cells from environment. A major protective mechanism that the corneal and conjunctival cells have developed is secretion of the innermost layer of the tear film, the mucous layer. Both the cornea and conjunctiva express membrane spanning mucins, whereas the conjunctiva also produces soluble mucins. The mucins present in the tear film serve to maintain the hydration of the ocular surface and to provide lubrication and anti-adhesive properties between the cells of the ocular surface and conjunctiva during the blink. A third function is to contribute to the epithelial barrier to prevent pathogens from binding to the ocular surface. This review will focus on the different types of mucins produced by the corneal and conjunctival epithelia. Also included in this review will be a presentation of the structure of mucins, regulation of mucin production, role of mucins in ocular surface diseases, and the differences in mucin production by the ocular surface, airways and gastrointestinal tract. PMID:23954166

  15. [Intraductal papillary mucinous neoplasm and recurrent pancreatitis].

    PubMed

    Gálvez, Eduardo; Gálvez, Gustavo; Barboza, Aurelio; Barboza, Eduardo; Combe, Juan Manuel; Combe, Mario R; Combe, Juan; Arias Stella C, Javier; Arias Stella, Javier

    2013-01-01

    Ohashi described for the first time the IPMN on 1982 as a pancreatic neoplasia with mucine cells forming papillae and producing dilatation of the main pancreatic duct or its branches. The IPMN represent the 1% of the pancreatic tumors and 5% of the cystic neoplasias. It is potentially malignant in a period of five years being more frequent in males between 60-70 and clinically these patients' presents as acute, recurrent or chronic pancreatitis, with an incidence of malignancy from 25% to 70%. CT scan and cholangio MRI allows the diagnosis, the variety, localization and possibility of determine malignancy. The treatment is the Whipple resection. We are reporting the case of an obese middle age male, being observed along the last 10 years because of recurrent pancreatitis with a cystic lesion of the head of the pancreas. The CT scan, endoscopic-ultrasound and the analysis of the liquid content suggested a mucinous lesion, reason why the patient underwent a pancreatic-duodenal resection. The histology study confirms the diagnosis of IPMN.

  16. Mucin glycan foraging in the human gut microbiome

    PubMed Central

    Tailford, Louise E.; Crost, Emmanuelle H.; Kavanaugh, Devon; Juge, Nathalie

    2015-01-01

    The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health. PMID:25852737

  17. Macromolecular properties and polymeric structure of canine tracheal mucins.

    PubMed Central

    Shankar, V; Virmani, A K; Naziruddin, B; Sachdev, G P

    1991-01-01

    Two high-Mr mucus glycoproteins (mucins), CTM-A and CTM-B, were highly purified from canine tracheal pouch secretions, and their macromolecular properties as well as polymeric structure were investigated. On SDS/composite-gel electrophoresis, a diffuse band was observed for each mucin. Polyacrylamide-gel electrophoresis using 6% gels also showed the absence of low-Mr contaminants in the mucins. Comparison of chemical and amino acid compositions revealed significant differences between the two mucins. Using a static-laser-light-scattering technique, CTM-A and CTM-B were found to have weight-average Mr values of about 11.0 x 10(6) and 1.4 x 10(6) respectively. Both mucins showed concentration-dependent aggregation in buffer containing 6 M-guanidine hydrochloride. Under similar experimental conditions, reduced-alkylated CTM-A had an Mr of 5.48 x 10(6) and showed no concentration-dependent aggregation. Hydrophobic properties of the mucins, investigated by the fluorescent probe technique using mansylphenylalanine as the probe, showed the presence of a large number of low-affinity (KD approx. 10(5) M) binding sites. These sites appeared to be located on the non-glycosylated regions of the protein core, since Pronase digestion of the mucins almost completely eliminated probe binding. Reduction of disulphide bonds of CTM-A and CTM-B did not significantly alter the probe-binding properties. Also, addition of increasing NaCl concentrations (0.03-1.0 M) to the buffer caused only a small change in the hydrophobic properties of native and reduced-alkylated mucins. CTM-A was deglycosylated, without notable in the hydrophobic properties of native and reduced-alkylated mucins. CTM-A was deglycosylated, without notable degradation, using a combination of chemical and enzymic methods. On SDS/PAGE the protein core was estimated to have an Mr of approx. 60,000. On the basis of the protein and carbohydrate contents of the major mucin CTM-A, the mucin monomer was calculated to have an

  18. Mucin-interacting proteins: from function to therapeutics

    PubMed Central

    Senapati, Shantibhusan; Das, Srustidhar; Batra, Surinder K.

    2010-01-01

    Mucins are high molecular weight glycoproteins that are involved in regulating diverse cellular activities both in normal and pathological conditions. Mucin activity and localization is mediated by several molecular mechanisms, including discrete interactions with other proteins. An understanding of the biochemistry behind the known interactions between mucins and other proteins, coupled with an appreciation of their pathophysiological significance, can lend insight into the development of novel therapeutic agents. Indeed, a recent study demonstrated that a cell permeable inhibitor, PMIP, which disrupts the MUC1–EGFR interaction, is effective in killing breast cancer cells in vitro and in tumor models. PMID:19913432

  19. In vivo gene transfer targeting in pancreatic adenocarcinoma with cell surface antigens

    PubMed Central

    2012-01-01

    Background Pancreatic ductal adenocarcinoma is a deadly malignancy resistant to current therapies. It is critical to test new strategies, including tumor-targeted delivery of therapeutic agents. This study tested the possibility to target the transfer of a suicide gene in tumor cells using an oncotropic lentiviral vector. Results Three cell surface markers were evaluated to target the transduction of cells by lentiviruses pseudotyped with a modified glycoprotein from Sindbis virus. Only Mucin-4 and the Claudin-18 proteins were found efficient for targeted lentivirus transductions in vitro. In subcutaneous xenografts of human pancreatic cancer cells models, Claudin-18 failed to achieve efficient gene transfer but Mucin-4 was found very potent. Human pancreatic tumor cells were modified to express a fluorescent protein detectable in live animals by bioimaging, to perform a direct non invasive and costless follow up of the tumor growth. Targeted gene transfer of a bicistronic transgene bearing a luciferase gene and the herpes simplex virus thymidine kinase gene into orthotopic grafts was carried out with Mucin-4 oncotropic lentiviruses. By contrast to the broad tropism VSV-G carrying lentivirus, this oncotropic lentivirus was found to transduce specifically tumor cells, sparing normal pancreatic cells in vivo. Transduced cells disappeared after ganciclovir treatment while the orthotopic tumor growth was slowed down. Conclusion This work considered for the first time three aspect of pancreatic adenocarcinoma targeted therapy. First, lentiviral transduction of human pancreatic tumor cells was possible when cells were grafted orthotopically. Second, we used a system targeting the tumor cells with cell surface antigens and sparing the normal cells. Finally, the TK/GCV anticancer system showed promising results in vivo. Importantly, the approach presented here appeared to be a safer, much more specific and an as efficient way to perform gene delivery in pancreatic tumors

  20. Influence of microemulsion-mucin interaction on the fate of microemulsions diffusing through pig gastric mucin solutions.

    PubMed

    Zhang, Jianbin; Lv, Yan; Wang, Bing; Zhao, Shan; Tan, Mingqian; Lv, Guojun; Ma, Xiaojun

    2015-03-02

    Mucus layer, a selective diffusion barrier, has an important effect on the fate of drug delivery systems in the gastrointestinal tract. To study the fate of microemulsions in the mucus layer, four microemulsion formulations with different particle sizes and lipid compositions were prepared. The microemulsion-mucin interaction was demonstrated by the fluorescence resonance energy transfer (FRET) method. Moreover, the microemulsions were observed aggregated into micron-sized emulsions by laser confocal microscopy. We concluded the microemulsion-mucin interaction not only led to microemulsions closely adhered to mucins but also destroyed the structure of microemulsions. At last, the diffusion of blank microemulsions and microemulsion-carried drugs (resveratrol and hymecromone) through mucin solutions was determined by the fluorescence recovery after photobleaching (FRAP) method and the Franz diffusion cell method. The results demonstrated the diffusion of microemulsions was significantly hindered by mucin solutions. The particle size of microemulsions had a negligible effect on the diffusion coefficients. However, the type of lipid played an important role, which could form hydrophobic interactions with mucins. Interestingly, microemulsion-carried drugs with different core/shell locations seemed to suffer different fates in the mucin solutions. The drug incorporated in the oil core of microemulsions, resveratrol, was transported through the mucus layer by the carriers, while the drug incorporated in the surfactant shell of microemulsions, hymecromone, was separated from the carriers and diffused toward the epithelium in the form of free molecules.

  1. Sarcomatoid carcinoma of the prostate: ductal adenocarcinoma and stromal sarcoma-like appearance: a rare association.

    PubMed

    Parada, David; Peña, Karla B; Riu, Francesc

    2011-01-01

    Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.

  2. Giant Magnons Meet Giant Gravitons

    SciTech Connect

    Hofman, Diego M.

    2008-07-28

    We study the worldsheet reflection matrix of a string attached to a D-brane in AdS{sub 5}xS{sup 5}. The D-brane corresponds to a maximal giant graviton that wraps an S{sup 3} inside S{sup 5}. In the gauge theory, the open string is described by a spin chain with boundaries. We focus on open strings with a large SO(6) charge and define an asymptotic boundary reflection matrix. Using the symmetries of the problem, we review the computation of the boundary reflection matrix, up to a phase. We also discuss weak and strong coupling computations where we obtain the overall phase factor and test our exact results.

  3. Is mucinous carcinoma of the colorectum a distinct genetic entity?

    PubMed Central

    Hanski, C.

    1995-01-01

    Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group. PMID:8519644

  4. Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases

    PubMed Central

    Reid, Michelle D; Basturk, Olca; Shaib, Walid L; Xue, Yue; Balci, Serdar; Choi, Hye-Jeong; Akkas, Gizem; Memis, Bahar; Robinson, Brian S; El-Rayes, Bassel F; Staley, Charles A; Staley, Christopher A; Winer, Joshua H; Russell, Maria C; Knight, Jessica H; Goodman, Michael; Krasinskas, Alyssa M; Adsay, Volkan

    2016-01-01

    High-grade versions of appendiceal goblet cell carcinoids (‘adenocarcinoma ex-goblet cell carcinoids’) are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29–84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n =3) and lung (n =1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed ‘other’ carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular (‘carcinoid pattern’) was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, ‘adenocarcinoma ex

  5. Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases.

    PubMed

    Reid, Michelle D; Basturk, Olca; Shaib, Walid L; Xue, Yue; Balci, Serdar; Choi, Hye-Jeong; Akkas, Gizem; Memis, Bahar; Robinson, Brian S; El-Rayes, Bassel F; Staley, Charles A; Staley, Christopher A; Winer, Joshua H; Russell, Maria C; Knight, Jessica H; Goodman, Michael; Krasinskas, Alyssa M; Adsay, Volkan

    2016-10-01

    High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is

  6. Absence of microsatellite instability in mucinous carcinomas of the breast.

    PubMed

    Lacroix-Triki, Magali; Lambros, Maryou B; Geyer, Felipe C; Suarez, Paula H; Reis-Filho, Jorge S; Weigelt, Britta

    2010-11-27

    Microsatellite instability (MSI) is a form of genetic instability that results from defects in DNA mismatch repair. MSI is reported to be rare in unselected breast cancers, however it is a common feature in subsets of colorectal, ovarian and endometrial cancers. In these anatomical sites, MSI-high carcinomas often display a mucinous histology. The aim of this study was to determine whether mucinous carcinomas of the breast would more frequently display MSI-high than invasive ductal carcinomas of no special type (IDC-NSTs). The expression of four MSI markers (i.e. MSH2, MSH6, MLH1 and PMS2) was immunohistochemically assessed in 35 mucinous breast carcinomas and 35 histological grade- and oestrogen receptor (ER) status-matched IDC-NSTs, and in a series of 245 invasive breast cancers. Cases were considered as potentially MSI-high if tumour cells lacked expression of at least two MSI markers and internal controls displayed nuclear staining. Nine mucinous carcinomas were microdissected and subjected to MSI analysis by PCR using the MSI markers BAT26 and BAT40. No immunohistochemical evidence of MSI-high was found in the 35 mucinous carcinomas and 35 grade- and ER-matched IDC-NSTs, and in the cohort of 245 invasive breast cancers. In addition, no evidence of MSI-high was observed by PCR analysis using the BAT26 and BAT40 markers in the nine mucinous carcinomas tested. Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous carcinomas of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.

  7. Mucins in neoplasms of pancreas, ampulla of Vater and biliary system

    PubMed Central

    Moschovis, Dimitrios; Bamias, Giorgos; Delladetsima, Ioanna

    2016-01-01

    Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN). Positive expression of MUC2 in intraductal papillary mucinus neoplasms (IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1, while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution. De novo MUC4 expression correlates to the severity of dysplasia in PanIN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas. In biliary intraepithelial neoplasia (BilIN), increased expression of MUC1 is associated with higher degrees of dysplasia. Intrahepatic cholangiocarcinomas (ICC) are characterized by increased expression of all glycoforms of MUC1. Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts (IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element. Absent MUC2 expression in any degree of BilIN may prove useful in differentiating them from IPNB. De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts (EHBDC). High de novo expression of MUC5AC is found in all degrees of BilIN and all types of IPNB and ICC. The MUC5AC is useful in the detection of neoplastic lesions of the bile duct at an early stage. Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater

  8. Chemically tunable mucin chimeras assembled on living cells

    DOE PAGES

    Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos; ...

    2015-09-29

    Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solvingmore » a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.« less

  9. Genetically engineered mucin mouse models for inflammation and cancer

    PubMed Central

    Joshi, Suhasini; Kumar, Sushil; Bafna, Sangeeta; Rachagani, Satyanarayana; Wagner, Kay-Uwe; Jain, Maneesh

    2015-01-01

    Mucins are heavily O-glycosylated proteins primarily produced by glandular and ductal epithelial cells, either in membrane-tethered or secretory forms, for providing lubrication and protection from various exogenous and endogenous insults. However, recent studies have linked their aberrant overexpression with infection, inflammation, and cancer that underscores their importance in tissue homeostasis. In this review, we present current status of the existing mouse models that have been developed to gain insights into the functional role(s) of mucins under physiological and pathological conditions. Knockout mouse models for membrane-associated (Muc1 and Muc16) and secretory mucins (Muc2) have helped us to elucidate the role of mucins in providing effective and protective barrier functions against pathological threats, participation in disease progression, and improved our understanding of mucin interaction with biotic and abiotic environmental components. Emphasis is also given to available transgenic mouse models (MUC1 and MUC7), which has been exploited to understand the context-dependent regulation and therapeutic potential of human mucins during inflammation and cancer. PMID:25634251

  10. Chemically tunable mucin chimeras assembled on living cells

    SciTech Connect

    Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos; Bertozzi, Carolyn R.

    2015-09-29

    Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solving a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.

  11. Salivary mucins promote the coexistence of competing oral bacterial species.

    PubMed

    Frenkel, Erica Shapiro; Ribbeck, Katharina

    2017-01-24

    Mucus forms a major ecological niche for microbiota in various locations throughout the human body such as the gastrointestinal tract, respiratory tract and oral cavity. The primary structural components of mucus are mucin glycoproteins, which crosslink to form a complex polymer network that surrounds microbes. Although the mucin matrix could create constraints that impact inhabiting microbes, little is understood about how this key environmental factor affects interspecies interactions. In this study, we develop an experimental model using gel-forming human salivary mucins to understand the influence of mucin on the viability of two competing species of oral bacteria. We use this dual-species model to show that mucins promote the coexistence of the two competing bacteria and that mucins shift cells from the mixed-species biofilm into the planktonic form. Taken together, these findings indicate that the mucus environment could influence bacterial viability by promoting a less competitive mode of growth.The ISME Journal advance online publication, 24 January 2017; doi:10.1038/ismej.2016.200.

  12. Viscous boundary lubrication of hydrophobic surfaces by mucin.

    PubMed

    Yakubov, Gleb E; McColl, James; Bongaerts, Jeroen H H; Ramsden, Jeremy J

    2009-02-17

    The lubricating behavior of the weakly charged short-side-chain glycoprotein mucin "Orthana" (Mw=0.55 MDa) has been investigated between hydrophobic and hydrophilic PDMS substrates using soft-contact tribometry. It was found that mucin facilitates lubrication between hydrophobic PDMS surfaces, leading to a 10-fold reduction in boundary friction coefficient for rough surfaces. The presence of mucin also results in a shift of the mixed lubrication regime to lower entrainment speeds. The observed boundary lubrication behavior of mucin was found to depend on the bulk concentration, and we linked this to the structure and dynamics of the adsorbed mucin films, which are assessed using optical waveguide light spectroscopy. We observe a composite structure of the adsorbed mucin layer, with its internal structure governed by entanglement. The film thickness of this adsorbed layer increases with concentration, while the boundary friction coefficient for rough surfaces was found to be inversely proportional to the thickness of the adsorbed film. This link between lubrication and structure of the film is consistent with a viscous boundary lubrication mechanism, i.e., a thicker adsorbed film, at a given sliding speed, results in a lower local shear rate and, hence, in a lower local shear stress. The estimated local viscosities of the adsorbed layer, derived from the friction measurements and the polymer layer density, are in agreement with each other.

  13. Clinicopathologic characteristics of mucinous carcinoma of the breast.

    PubMed

    Hanagiri, Takeshi; Ono, Kenji; Baba, Teturo; So, Tetsuya; Yamasaki, Masaharu; Nagata, Yoshika; Uramoto, Hidetaka; Takenoyama, Mitsuhiro; Yasumoto, Kosei

    2010-01-01

    The mucinous carcinoma of breast cancer is a relatively rare malignant tumor. This study investigated the clinical and pathologic features of mucinous carcinoma. The medical records of 237 patients with invasive breast cancer who underwent surgery between 1995 and 2006 were reviewed. These cases included 10 patients (4.2%) with mucinous carcinoma. The age of the patients ranged from 43 to 71 years (mean, 55.5 years). The tumor size was T1 in 5 patients and T2 in 5 patients. Lymph node metastasis was diagnosed as being negative in 9 patients and positive in 1 patient. Six patients (60%) were positive both for estrogen and progesterone receptor. The 10-year survival rates of mucinous carcinoma and other types of invasive breast cancer were 87.5% and 80.7%, respectively. Mucinous carcinoma showed a lower incidence of lymph node metastasis than other types of invasive breast cancer. Mucinous carcinoma tended to have a better prognosis in comparison with other types of invasive breast carcinoma.

  14. Developmental expression of mucin genes in the human gastrointestinal system

    PubMed Central

    Reid, C; Harris, A

    1998-01-01

    Background and aims—Mucin glycoproteins play a key role in the normal function of the epithelium lining the gastrointestinal tract. The expression of mucin genes, MUC 3, 4, 5AC, 5B, 6, 7, and 8 in human fetal tissues was examined to establish the localisation and age of onset of expression of each mucin gene during human development. 
Methods—Mucin gene expression was assayed by mRNA in situ hybridisation. 
Results—Expression of MUC3 was detected in the small intestine and colon from 13 weeks gestation onwards and at low levels in the main pancreatic duct at 13 weeks only. MUC4 expression was seen at a low level in the colonic epithelium from 13 weeks of gestation but not elsewhere in the gastrointestinal tract. MUC5AC mRNA was detected in the colon at 17 weeks and at high levels in the stomach at 23 weeks. MUC6 transcripts were evident in the pancreatic ducts from 13 weeks of gestation and at high levels in the stomach at 23 weeks. MUC5B, MUC7, and MUC8 transcripts were not detected. 
Conclusions—Mucin genes are expressed from the early mid-trimester of gestation in the developing human fetal gastrointestinal tract. 

 Keywords: mucin; developmental expression; gastrointestinal tract PMID:9536947

  15. Gastric type endocervical adenocarcinoma: an aggressive tumor with unusual metastatic patterns and poor prognosis

    PubMed Central

    Karamurzin, Yevgeniy S.; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R.; Patel, Prusha; Pike, Malcolm C.; Soslow, Robert A.; Park, Kay J.

    2016-01-01

    Gastric type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV-associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of three institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (one Li-Fraumeni, one Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II–IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least one site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 months); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease specific survival at 5 years was 42% for GAS vs. 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon. PMID:26457350

  16. A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix.

    PubMed

    Hara, Kieko; Saito, Tsuyoshi; Hayashi, Takuo; Yimit, Alkam; Takahashi, Michiko; Mitani, Keiko; Takahashi, Makoto; Yao, Takashi

    2015-09-01

    Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs. We examined 16 AMTs (11 LAMNs and 5 MACs) for genetic alterations of GNAS, KRAS, BRAF, TP53, CTNNB1, and TERT promoter in order to elucidate the possibility of a shared genetic background in the two tumor types. Extensive histological examination revealed the presence of a low-grade component in all cases of MAC. GNAS mutations were detected in two LAMNs and in one MAC, although the GNAS mutation in this MAC was a nonsense mutation (Q227X) expected not to be activating mutation. TP53 mutations were detected in three LAMNs; they were frequently detected in MACs. KRAS mutations were detected in three LAMNs and three MACs, and CTNNB1 mutations were detected in two LAMNs. KRAS mutation and activating mutation of GNAS occurred exclusively in AMTs. BRAF and TERT mutations were not detected. Overexpression of p53 was observed in only two MACs, and p53 immunostaining clearly discriminated the high-grade lesion from a low-grade component in one. These findings suggest that p53 overexpression plays an important role in the carcinogenesis of AMTs and that, in addition to mutations of GNAS, KRAS and TP53 alterations might be shared by AMTs, thus providing evidence for the possible progression of LAMNs to MAC.

  17. Long-term Effect of Radiotherapy in Rectal Cancer Patients with Mucinous Tumor: A Large Population Based Study

    PubMed Central

    Guan, Xu; Jia, Senhao; Chen, Wei; Jiang, Zheng; Liu, Zheng; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2017-01-01

    Due to distinct biological behavior of mucinous adenocarcinoma (MAC) and signet ring cell cancer (SRC), the efficacy of radiotherapy on long-term outcome for rectal cancer (RC) patients with mucinous tumors is still unclear. Here, we identified 1808 RC patients with MAC/SRC from Surveillance, Epidemiology, and End-Results (SEER) database from 2004 to 2013. Patients were divided into two subgroups according to different therapeutic strategies, including surgery alone and surgery combined with radiotherapy. Kaplan–Meier methods and Cox regression models were used to access the influence of therapeutic strategy on long-term survival outcomes. The 5-year and 10-year cancer specific survival (CSS) were improved in stage II and III patients who underwent surgery and radiotherapy compared with patients who underwent surgery alone. These results were further confirmed following propensity score matching. In addition, radiotherapy was deemed as independent good prognostic factor in patient with MAC/SRC. In subgroup analysis, the result also demonstrated that long-term survival was improved following radiotherapy. However, there was no prognostic difference between preoperative and postoperative radiotherapy. In conclusion, radiotherapy could improve survival for RC patients with MAC and SRC, but only for patients in stage II and III. This finding supported the application of radiotherapy in clinical practice. PMID:28272410

  18. Transforming giants.

    PubMed

    Kanter, Rosabeth Moss

    2008-01-01

    Large corporations have long been seen as lumbering, inflexible, bureaucratic--and clueless about global developments. But recently some multinationals seem to be transforming themselves: They're engaging employees, moving quickly, and introducing innovations that show true connection with the world. Harvard Business School's Kanter ventured with a research team inside a dozen global giants--including IBM, Procter & Gamble, Omron, CEMEX, Cisco, and Banco Real--to discover what has been driving the change. After conducting more than 350 interviews on five continents, she and her colleagues came away with a strong sense that we are witnessing the dawn of a new model of corporate power: The coordination of actions and decisions on the front lines now appears to stem from widely shared values and a sturdy platform of common processes and technology, not from top-down decrees. In particular, the values that engage the passions of far-flung workforces stress openness, inclusion, and making the world a better place. Through this shift in what might be called their guidance systems, the companies have become as creative and nimble as much smaller ones, even while taking on social and environmental challenges of a scale that only large enterprises could attempt. IBM, for instance, has created a nonprofit partnership, World Community Grid, through which any organization or individual can donate unused computing power to research projects and see what is being done with the donation in real time. IBM has gained an inspiring showcase for its new technology, helped business partners connect with the company in a positive way, and offered individuals all over the globe the chance to contribute to something big.

  19. Human milk mucin 1 and mucin 4 inhibit Salmonella enterica serovar Typhimurium invasion of human intestinal epithelial cells in vitro.

    PubMed

    Liu, Bo; Yu, Zhuoteng; Chen, Ceng; Kling, David E; Newburg, David S

    2012-08-01

    Many human milk glycans inhibit pathogen binding to host receptors and their consumption by infants is associated with reduced risk of disease. Salmonella infection is more frequent among infants than among the general population, but the incidence is lower in breast-fed babies, suggesting that human milk could contain components that inhibit Salmonella. This study aimed to test whether human milk per se inhibits Salmonella invasion of human intestinal epithelial cells in vitro and, if so, to identify the milk components responsible for inhibition. Salmonella enterica serovar Typhimurium SL1344 (SL1344) invasion of FHs 74 Int and Caco-2 cells were the models of human intestinal epithelium infection. Internalization of fluorescein-5-isothiocyanate-labeled SL1344 into intestinal cells was measured by flow cytometry to quantify infection. Human milk and its fractions inhibited infection; the inhibitory activity localized to the high molecular weight glycans. Mucin 1 and mucin 4 were isolated to homogeneity. At 150 μg/L, a typical concentration in milk, human milk mucin 1 and mucin 4 inhibited SL1344 invasion of both target cell types. These mucins inhibited SL1344 invasion of epithelial cells in a dose-dependent manner. Thus, mucins may prove useful as a basis for developing novel oral prophylactic and therapeutic agents that inhibit infant diseases caused by Salmonella and related pathogens.

  20. Magnetic resonance imaging findings of undifferentiated carcinoma with osteoclast-like giant cells of pancreas.

    PubMed

    Yang, Kyung Yoon; Choi, Joon-Il; Choi, Moon Hyung; Park, Michael Yong; Rha, Sung Eun; Byun, Jae Young; Jung, Eun Sun; Lall, Chandana

    2016-01-01

    Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic and periampullary neoplasm with less than 50 cases reported in the literature. Pathologically, this tumor mimics a giant cell tumor in bones. We report a case of undifferentiated carcinoma with osteoclast-like giant cells in a 55-year-old man presenting as a pancreatic mass with associated regional and distant lymphadenopathy. On T1- and T2-weighted images, the mass shows dark signal intensity which was atypical for a pancreatic adenocarcinoma.

  1. Early-Onset Signet-Ring Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

    PubMed Central

    Khan, Maliha; Korphaisarn, Krittiya; Saif, Aneeqa; Foo, Wai C.

    2017-01-01

    Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in the United States. While a decline has been observed in the older population, the occurrence of CRC in the adolescent and young adult (AYA) population has increased over the past two decades. The histopathologic characteristics and clinical behavior of CRC in AYA patients have been shown to be distinct from those of CRC in older adults. The rarer subtypes of CRC such as mucinous adenocarcinoma and signet-ring cell carcinoma are associated with a poorer prognosis compared to the more common subtypes. Here we report a case of a 20-year-old man who was diagnosed with stage IVB (T4 N2 M1, with peritoneal carcinomatosis) signet-ring cell adenocarcinoma of the colon. The scarcity of information on these rarer subtypes merits further study and investigation. PMID:28326211

  2. Giant Cell Arteritis

    MedlinePlus

    Giant cell arteritis is a disorder that causes inflammation of your arteries, usually in the scalp, neck, and arms. ... arteries, which keeps blood from flowing well. Giant cell arteritis often occurs with another disorder called polymyalgia ...

  3. [Endoscopic diagnosis of Barrett's adenocarcinoma].

    PubMed

    Yoshio, H; Takashi, Y; Mitsuyo, H; Nobuhiko, Y; Tatsurou, T; Kazuhiko, S; Yoko, H; Shigemasa, I; Hisanaga, M; Osamu, H; Katsuyoshi, S; Seishi, U; Matsushita, H; Masahiko, T

    1999-03-01

    Biopsy specimens can reveal that esophageal cancer is an adenocarcinoma but they cannot show that its origin is Barrett's mucosa. Therefore we must show during endoscopy that the tumor exists in Barrett's mucosa. We reported that Barrett's esophagus could be clearly diagnosed at endoscopy as the columnar mucosa lying on the longitudinal vessels in the lower esophagus. We define Barrett's esophagus as "the columnar mucosa in the esophagus which exists continuously more than 2 cm in circumference from the stomach." Short-segment Barrett's esophagus (SSBE) is "the columnar mucosa which exists in the esophagus continuously from the stomach but its length has a part under 2 cm in length." Endoscopically Barrett's adenocarcinoma is visualized as a lesion with a reddish and uneven mucosal surface. Barrett's adenocarcinomas occur in the SSBE as well. Endoscopic observation at periodic intervals is necessary not only for cases with Barrett's esophagus but also with SSBE. A further examination is necessary to determine the application of EMR for superficial Barrett's adenocarcinoma.

  4. Favorable control of advanced colon adenocarcinoma with severe bone marrow metastasis: A case report

    PubMed Central

    Hanamura, Fumiyasu; Shibata, Yoshihiro; Shirakawa, Tsuyoshi; Kuwayama, Miyuki; Oda, Hisanobu; Ariyama, Hiroshi; Taguchi, Kenichi; Esaki, Taito; Baba, Eishi

    2016-01-01

    Colorectal cancer (CRC) has a propensity to metastasize to the liver, lungs and regional abdominal lymph nodes, but rarely to the bone marrow. A 60-year-old man presented to the National Hospital Organization Kyushu Cancer Center with a 4-week history of persistent lower back pain, anorexia and difficulty defecating. Complete blood count revealed severe thrombocytopenia and erythroblastosis, suggesting a hematological malignancy. However, the bone marrow examination demonstrated involvement by a moderately to poorly differentiated adenocarcinoma, but no hematopoietic abnormalities. A computed tomography scan revealed thickening of the wall of the sigmoid colon, with para-aortic, hilar, mediastinal and supraclavicular lymphadenopathy. The patient was thus diagnosed with sigmoid colon adenocarcinoma with lymph node and bone marrow metastasis. Modified FOLFOX6 was promptly initiated, with concurrent therapy for disseminated intravascular coagulation (DIC). An increased number of thrombocytes was observed on day 6. After 3 cycles of treatment, the patient recovered from DIC and the levels of serum carcinoembryonic antigen and cytokeratin 19 fragment were decreased. Tumor biopsy during colonoscopy following recovery from DIC demonstrated poorly differentiated adenocarcinoma with mucin production, without mutations in the RAS, BRAF or PIK3CA genes, and a cytokeratin (CK) 7-negative, CK20-positive phenotype. The patient has been treated with chemotherapy for 150 days without disease progression. However, the efficacy of chemotherapy for rarely encountered bone marrow metastasis from CRC is poor. The present case was favorably maintained on chemotherapy and survived for 10 months. PMID:27900088

  5. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2013-10-01

    The 2009 impact and recent superbolides on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution {enabling the 2009 impact debris field detection} and rapid frame rates {enabling the 2010/2012 impact flash detections and lightcurve measurements}.We propose a ToO program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere {10^20 J}.HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing {not achievable from the ground} is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  6. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2014-10-01

    The 2009 impact and recent superbolides on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution (enabling the 2009 impact debris field detection) and rapid frame rates (enabling the 2010/2012 impact flash detections and lightcurve measurements).We propose a ToO program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere (10^20 J).HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing (not achievable from the ground) is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  7. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2012-10-01

    The 2009 impact on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution {enabling the 2009 impact debris field detection} and rapid frame rates {enabling the 2010 impact flash detections and lightcurve measurements}.We propose a Target of Opportunity program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere.HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing {not achievable from the ground} is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  8. Multidisciplinary approach to diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Sahani, Dushyant V; Lin, Dana J; Venkatesan, Aradhana M; Sainani, Nisha; Mino-Kenudson, Mari; Brugge, William R; Fernandez-Del-Castillo, Carlos

    2009-03-01

    Intraductal papillary mucinous neoplasms have gained recognition in recent years as premalignant precursors to pancreatic cancer that enable early detection and often are found incidentally at imaging. Accurate diagnosis and optimal, finely tuned management of these lesions are important and require collaboration across various disciplines, including radiology, endoscopy, surgery, and pathology. Several imaging modalities can visualize these lesions adequately, each with specific advantages and disadvantages. Multidetector computed tomography and magnetic resonance cholangiopancreatography are generally the first-line imaging modalities; endoscopic imaging such as endoscopic ultrasound and endoscopic retrograde cholangiopancreatography are beneficial when the former 2 modalities are equivocal. Surgical candidates generally include patients with main duct lesions or branch duct lesions greater than 3 cm or any possessing a solid component. A management algorithm indicating when surgery should be pursued is proposed. For nonsurgical and postsurgical patients, follow-up management is important to monitor growth and recurrence, and risks from repeated radiation exposure should be taken into account. Furthermore, issues of multifocality and increased predisposition of the pancreas to ductal adenocarcinoma must be addressed at follow-up evaluation. A follow-up management algorithm also is proposed in this review.

  9. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    PubMed

    Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

    2015-10-01

    c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors.

  10. Physical and chemical characteristics of mucin secreted by pseudomyxoma peritonei (PMP)

    PubMed Central

    Pillai, Krishna; Akhter, Javed; Mekkawy, Ahmed; Chua, Terence C; Morris, David L

    2017-01-01

    Background: Pseudomyxoma peritonei (PMP) is a rare disease with excess intraperitoneal mucin secretion. Treatment involves laparotomy, cytoreduction and chemotherapy that is very invasive with patients often acquiring numerous compromises. Hence a mucolytic comprising of bromelain and N-acetyl cystein has been developed to solubilise mucin in situ for removal by catherization. Owing to differences in mucin appearance and hardness, dissolution varies. Therefore the current study investigates the inter-mucin physical and chemical characteristics, in order to reformulate an effective mucolytic for all mucin. Method: PMP mucin, from the three categories (soft, semi hard and hard mucin) was solubilised and then various physical characteristics such as turbidity, density, kinematic viscosity were measured. The water content and the density of solid mucin were also determined. This was followed by the determination of sialic acid, glucose, lipid, Thiol (S-S and S-H) content of the samples. Lastly, the distribution of MUC2, MUC5B and MUC5AC was determined using western blot technique. Results: Both turbidity and kinematic viscosity and sialic acid content increased linearly as the hardness of mucin increased. However, density, hydration, protein, glucose, lipid and sulfhydryl and disulphide content decreased linearly as hardness of mucin increased. The distribution ratio of mucins (MUC2:MUC5B:MUC5AC) in soft mucin is 2.25:1.5:1.0, semi hard mucin is 1:1:1 and hard mucin is 3:2:1. Conclusion: The difference in texture and hardness of mucin may be due to cellular content, hydration, glucose, protein, lipids, thiol and MUC distribution. Soft mucin is solely made of glycoprotein whilst the others contained cellular materials. PMID:28138305

  11. Ocular melanoma and mammary mucinous carcinoma in an African lion

    PubMed Central

    2012-01-01

    Background Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. Case presentation An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. Conclusions This is the first description of these tumor in African lions. PMID:23009723

  12. Mucin biopolymers as broad-spectrum antiviral agents

    PubMed Central

    Lieleg, Oliver; Lieleg, Corinna; Bloom, Jesse; Buck, Christopher B.; Ribbeck, Katharina

    2012-01-01

    Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system. PMID:22475261

  13. Gelation of mucin: Protecting the stomach from autodigestion

    NASA Astrophysics Data System (ADS)

    Bansil, Rama

    2011-03-01

    In this talk I will describe the molecular mechanisms involved in the remarkable ability of the mucus lining of the stomach for protecting the stomach from being digested by the acidic gastric juices that it secretes. These physical properties can be attributed to the presence of a high molecular weight glycoprotein found in mucus, called mucin. Rheology and other measurements show that gastric mucin forms a gel under acidic pH. A model of gelation based on the interplay of hydrophobic and electrostatic interactions will be discussed. Molecular Dynamics simulation studies of folding and aggregation of mucin domains provide further support for this model. The relevance of gelation to the motion of the ulcer causing bacterium H. pylori will be discussed.

  14. Mechanical intestinal obstruction secondary to appendiceal mucinous cystadenoma

    PubMed Central

    Xu, Zheng-shui; Xu, Wei; Ying, Jia-qi; Cheng, Hua

    2017-01-01

    Abstract Background: Appendiceal mucinous cystadenoma can present in various ways, and it is most commonly encountered incidentally during appendectomy, but mechanical intestinal obstruction secondary to an appendiceal mucocele has been rarely reported. Methods: We report a case of mechanical intestinal obstruction secondary to appendiceal mucinous cystadenoma. After nasogastric decompression and initial aggressive intravenous fluid resuscitation, an emergency operation was performed under the diagnosis of acute mechanical intestinal obstruction. Results: We performed an appendectomy and intraoperative enteral decompression without anastomoses. The pathologic examination (PE) revealed appendiceal mucinous cystadenoma. After the operation, the patient's recovery went smoothly, and the patient was discharged on the fifth postoperative day. No tumor recurrence was recorded over an 8 month follow-up period. Conclusion: Early operative intervention should be recommended to the patient with acute mechanical complete intestinal obstruction, especially the patient who had no previous abdominal surgery. And it is vital to discriminate benign and malignantappendiceal mucocel in determining the extent of surgery. PMID:28151903

  15. Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mucins are large glycoproteins implicated in protection of all mucosal surfaces. In humans and rodents, the mucin gene family has been well described and previous studies have investigated the distribution and function of mucins in the respiratory, urogenital and gastrointestinal (GI) tracts. In con...

  16. Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules

    PubMed Central

    Sesma, Juliana I.; Kreda, Silvia M.; Okada, Seiko F.; van Heusden, Catharina; Moussa, Lama; Jones, Lisa C.; O'Neal, Wanda K.; Togawa, Natsuko; Hiasa, Miki; Moriyama, Yoshinori

    2013-01-01

    Nucleotides within the airway surface liquid promote fluid secretion via activation of airway epithelial purinergic receptors. ATP is stored within and released from mucin granules as co-cargo with mucins, but the mechanism by which ATP, and potentially other nucleotides, enter the lumen of mucin granules is not known. We assessed the contribution of the recently identified SLC17A9 vesicle nucleotide transporter (VNUT) to the nucleotide availability within isolated mucin granules and further examined the involvement of VNUT in mucin granule secretion-associated nucleotide release. RT-PCR and Western blot analyses indicated that VNUT is abundantly expressed in airway epithelial goblet-like Calu-3 cells, migrating as a duplex with apparent mobility of 55 and 60 kDa. Subcellular fractionation studies indicated that VNUT55 was associated with high-density mucin granules, whereas VNUT60 was associated with low-density organelles. Immunofluorescence studies showed that recombinant VNUT localized to mucin granules and other organelles. Mucin granules isolated from VNUT short hairpin RNA-expressing cells exhibited a marked reduction of ATP, ADP, AMP, and UTP levels within granules. Ca2+-regulated vesicular ATP release was markedly reduced in these cells, but mucin secretion was not affected. These results suggest that VNUT is the relevant nucleotide transporter responsible for the uptake of cytosolic nucleotides into mucin granules. By controlling the entry of nucleotides into mucin granules, VNUT contributes to the release of purinergic signaling molecules necessary for the proper hydration of co-released mucins. PMID:23467297

  17. Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules.

    PubMed

    Sesma, Juliana I; Kreda, Silvia M; Okada, Seiko F; van Heusden, Catharina; Moussa, Lama; Jones, Lisa C; O'Neal, Wanda K; Togawa, Natsuko; Hiasa, Miki; Moriyama, Yoshinori; Lazarowski, Eduardo R

    2013-05-15

    Nucleotides within the airway surface liquid promote fluid secretion via activation of airway epithelial purinergic receptors. ATP is stored within and released from mucin granules as co-cargo with mucins, but the mechanism by which ATP, and potentially other nucleotides, enter the lumen of mucin granules is not known. We assessed the contribution of the recently identified SLC17A9 vesicle nucleotide transporter (VNUT) to the nucleotide availability within isolated mucin granules and further examined the involvement of VNUT in mucin granule secretion-associated nucleotide release. RT-PCR and Western blot analyses indicated that VNUT is abundantly expressed in airway epithelial goblet-like Calu-3 cells, migrating as a duplex with apparent mobility of 55 and 60 kDa. Subcellular fractionation studies indicated that VNUT55 was associated with high-density mucin granules, whereas VNUT60 was associated with low-density organelles. Immunofluorescence studies showed that recombinant VNUT localized to mucin granules and other organelles. Mucin granules isolated from VNUT short hairpin RNA-expressing cells exhibited a marked reduction of ATP, ADP, AMP, and UTP levels within granules. Ca(2+)-regulated vesicular ATP release was markedly reduced in these cells, but mucin secretion was not affected. These results suggest that VNUT is the relevant nucleotide transporter responsible for the uptake of cytosolic nucleotides into mucin granules. By controlling the entry of nucleotides into mucin granules, VNUT contributes to the release of purinergic signaling molecules necessary for the proper hydration of co-released mucins.

  18. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  19. Oncocytic Adenocarcinoma of the Orbit.

    PubMed

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  20. Aspergillosis and the role of mucins in cystic fibrosis.

    PubMed

    Cowley, Abigail C; Thornton, David J; Denning, David W; Horsley, Alexander

    2017-04-01

    The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A. fumigatus contributes to CF lung disease remain largely unclear. As the first point of contact within the lung, and an important component of the innate immune system, it is likely that the mucus barrier plays an important role in this process. Study of the functional interplay between this vital protective barrier, and in particular its principal structural components, the polymeric gel-forming mucins, and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus protease activity has been shown to upregulate mucus production by inducing mucin mRNA and protein expression, and A. fumigatus proteases and glycosidases are able to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties to promote fungal colonization of the airways and/or utilize mucins as a nutrient source. Moreover, conidial surface lectin binding to mucin glycans is a key aspect of clearance of Aspergillus from the lung in health but may be an important aspect of colonization, where mucociliary clearance is compromised, as in the CF lung. Here we discuss the nature of the mucus barrier and its mucin components in CF, and how they may be implicated in A. fumigatus infection. Pediatr Pulmonol 2017;52:548-555. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.

  1. Optimal lymphadenectomy for esophageal adenocarcinoma.

    PubMed

    Oezcelik, A

    2013-08-01

    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  2. The Electric Giant Resonances

    NASA Astrophysics Data System (ADS)

    van der Woude, A.

    The following sections are included: * Introduction * Experimental Methods to Study Giant Resonances * Introduction * The Tools * Introduction * Tools for Isoscalar Scattering * INELASTIC α-SCATTERING * INELASTIC PROTON SCATTERING * Tools for Isovector Excitations * γ-ABSORPTION AND PARTICLE CAPTURE REACTIONS * CHARGE EXCHANGE REACTIONS - THE (π+, π0) REACTION * Tools For Isoscalar And Isovector Excitations * INELASTIC ELECTRON SCATTERING * GIANT RESONANCE EXCITATION BY FAST HEAVY IONS * From Multipole Cross Section To Multipole Strength * The Electric Isoscalar Resonances * The Isoscalar Giant Monopole Resonance * Systematics on the GMR * Compressibility and the Giant Monopole Resonance * Introduction * The Compressibility of nuclear matter from the GMR energies * Discussion * The Isoscalar Giant Quadrupole Resonance * General Trends In Medium-Heavy and Heavy Nuclei * The GQR In Light Nuclei * The Isoscalar 3- Strength, LEOR and HEOR * Isoscalar 4+ Strength * Miscellaneous; Isoscalar 1- and L > 4-Strength * The Electric Isovector Giant Resonances * The Isovector Giant Dipole Resonance: GDR * The Isovector Giant Monopole Resonances: IVGMR * The Isovector Quadrupole Resonance: IVGQR * The Effect of Ground State Deformation on the Shape of Giant Resonance: Microscopic Picture * Giant Resonances Built on Excited States * Introduction * Capture Reactions on Light Nuclei * Statistical decay of GDR γ Emission in Heavy Compound Systems * Introduction * Theoretical Predictions * Some Experimental Results * Summary and Outlook * Acknowledgements * General References * References

  3. [Intraductal papillary mucinous neoplasm of the pancreas, IPMN].

    PubMed

    Sirén, Jukka

    2013-01-01

    With the development and increasing use of imaging techniques, intraductal papillary mucinous neoplasm (IPMN) is being detected with increasing frequency. Two forms of the disease are distinguished, the rare main duct form and the common accessory pancreatic duct form. The former often progresses to malignancy, the latter only seldom. The mixed form of IPMN exhibits features of both forms. In main duct IPMN, mucin production obstructs the pancreatic duct causing its dilatation and often symptoms typical of chronic pancreatitis. Main duct IPMN is always an indication for surgery, whereas monitoring is often sufficient for side duct IPMN.

  4. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  5. Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    PubMed

    Jambal, Purevsuren; Badtke, Melanie M; Harrell, J Chuck; Borges, Virginia F; Post, Miriam D; Sollender, Grace E; Spillman, Monique A; Horwitz, Kathryn B; Jacobsen, Britta M

    2013-01-01

    Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor biology and relationship to invasive disease of other subtypes. We have now developed a human breast cancer cell line called BCK4, in which we can control the behavior of MBC. BCK4 cells were derived from a patient whose poorly differentiated primary tumor was treated with chemotherapy, radiation and tamoxifen. Malignant cells from a recurrent pleural effusion were xenografted in mammary glands of a nude mouse. Cells from the solid tumor xenograft were propagated in culture to generate the BCK4 cell line. Multiple marker and chromosome analyses demonstrate that BCK4 cells are human, near diploid and luminal, expressing functional estrogen, androgen, and progesterone receptors. When xenografted back into immunocompromised cycling mice, BCK4 cells grow into small pure MBC. However, if mice are supplemented with continuous estradiol, tumors switch to invasive lobular carcinoma (ILC) with mucinous features (mixed MBC), and growth is markedly accelerated. Tamoxifen prevents the expansion of this more invasive component. The unexpected ability of estrogens to convert pure MBC into mixed MBC with ILC may explain the rarity of the pure disease in premenopausal women. These studies show that MBC can be derived from lobular precursors and that BCK4 cells are new, unique models to study the phenotypic plasticity, hormonal regulation, optimal therapeutic interventions, and metastatic patterns of MBC.

  6. Metastatic adenocarcinoma of unknown primary origin.

    PubMed

    Hammar, S P

    1998-12-01

    Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site. Some metastatic adenocarcinomas have distinctive histological features that allow for their site determination (eg, colonic adenocarcinoma, bronchioloalveolar cell carcinoma), although the majority of metastatic adenocarcinomas have histological features that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic adenocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin, intranuclear surfactant apoprotein tubular inclusions, Clara cell granules, uniform short microvilli with filamentous cores and core rootlets, Langerhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ultrastructural features are absolutely specific. Relatively specific immunohistochemical tests used to diagnose metastatic adenocarcinomas of unknown primary origin include prostate-specific antigen, thyroglobulin, estrogen and progesterone receptor proteins, thyroid transcription factor-I, and surfactant apoproteins. Of these, prostate-specific antigen and thyroglobulin are the most specific. The purpose of this article is to discuss the use of electron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin.

  7. Intraductal Papillary Mucinous Neoplasm of Pancreas

    PubMed Central

    Machado, Norman Oneil; al Qadhi, Hani; al Wahibi, Khalifa

    2015-01-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are neoplasms that are characterized by ductal dilation, intraductal papillary growth, and thick mucus secretion. This relatively recently defined pathology is evolving in terms of its etiopathogenesis, clinical features, diagnosis, management, and treatment guidelines. A PubMed database search was performed. All the relevant abstracts in English language were reviewed and the articles in which cases of IPMN could be identified were further scrutinized. Information of IPMN was derived, and duplication of information in several articles and those with areas of persisting uncertainties were excluded. The recent consensus guidelines were examined. The reported incidence of malignancy varies from 57% to 92% in the main duct-IPMN (MD-IPMN) and from 6% to 46% in the branch duct-IPMN (BD-IPMN). The features of high-risk malignant lesions that raise concern include obstructive jaundice in a patient with a cystic lesion in the pancreatic head, the findings on radiological imaging of a mass lesion of >30 mm, enhanced solid component, and the main pancreatic duct (MPD) of size ≥10 mm; while duct size 5-9 mm and cyst size <3 mm are considered as “worrisome features.” Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are primary investigations in diagnosing and following up on these patients. The role of pancreatoscopy and the analysis of aspirated cystic fluid for cytology and DNA analysis is still to be established. In general, resection is recommended for most MD-IPMN, mixed variant, and symptomatic BD-IPMN. The 5-year survival of patients after surgical resection for noninvasive IPMN is reported to be at 77-100%, while for those with invasive carcinoma, it is significantly lower at 27-60%. The follow-up of these patients could vary from 6 months to 1 year and would depend on the risk stratification for invasive malignancy and the pathology of the resected specimen. The understanding of

  8. Polyomavirus (BK)-associated pleomorphic giant cell carcinoma of the urinary bladder: a case report.

    PubMed

    Alexiev, Borislav A; Papadimitriou, John C; Chai, Toby C; Ramos, Emilio; Staats, Paul N; Drachenberg, Cinthia B

    2013-04-01

    This report describes the morphological features of a pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder in a male, 12 years post living related donor renal transplant. The voided urine cytology demonstrated rare decoy cells admixed with markedly atypical urothelial cell clusters, papillae and giant cells. Cystoprostatectomy demonstrated a nodular mass involving the trigone and right lateral-posterior wall, adjacent to the ureteral orifice. Hematoxylin-eosin stained sections showed two synchronous malignancies: (a) pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder, metastatic to the omentum and (b) prostatic adenocarcinoma, Gleason score 3+4=7, involving the right prostate lobe. Strong diffuse expression of polyomavirus large T antigen was demonstrated in the primary and metastatic pleomorphic giant cell carcinoma, supporting a possible role for polyomavirus (BK) in the oncogenetic pathway. The prostatic adenocarcinoma was negative for polyomavirus large T antigen. Our findings of p63, CK7 and CK903 expression in pleomorphic giant cell carcinoma suggest that the tumor is of urothelial derivation. This is the first report describing the morphological features of urinary bladder pleomorphic giant cell carcinoma with trophoblastic differentiation, positive for polyomavirus large T antigen, arising in the background of BKV reactivation.

  9. Mucinous Cystadenoma of the Testis: A Case Report with Immunohistochemical Findings

    PubMed Central

    Kim, Gilhyang; Kwon, Dohee; Na, Hee Young; Kim, Sehui; Moon, Kyung Chul

    2017-01-01

    Mucinous cystadenoma of the testis is a very rare tumor. Herein, we report a case of mucinous cystadenoma arising in the testis of a 61-year-old man, along with a literature review. Computed tomography showed a 2.5-cm-sized poorly enhancing cystic mass. Grossly, the tumor was a unilocular cystic mass filled with mucinous material and confined to the testicular parenchyma. Histologically, the cyst had a fibrotic wall lined by mucinous columnar epithelium without atypia. Immunohistochemical staining was positive for cytokeratin 20 and CDX2, as well as focally positive for cytokeratin 7. The pathologic diagnosis was mucinous cystadenoma. PMID:28189139

  10. MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions

    PubMed Central

    Hernandez, Yasmin G; Lucas, Aimee L

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the 4th deadliest cancer in the United States, due to its aggressive nature, late detection, and resistance to chemotherapy. The majority of PDAC develops from 3 precursor lesions, pancreatic intraepithelial lesions (PanIN), intraductual papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm. Early detection and surgical resection can increase PDAC 5-year survival rate from 6% for Stage IV to 50% for Stage I. To date, there are no reliable biomarkers that can detect PDAC. MicroRNAs (miRNA) are small noncoding RNAs (18-25 nucleotides) that regulate gene expression by affecting translation of messenger RNA (mRNA). A large body of evidence suggests that miRNAs are dysregulated in various types of cancers. MiRNA has been profiled as a potential biomarker in pancreatic tumor tissue, blood, cyst fluid, stool, and saliva. Four miRNA biomarkers (miR-21, miR-155, miR-196, and miR-210) have been consistently dysregulated in PDAC. MiR-21, miR-155, and miR-196 have also been dysregulated in IPMN and PanIN lesions suggesting their use as early biomarkers of this disease. In this review, we explore current knowledge of miRNA sampling, miRNA dysregulation in PDAC and its precursor lesions, and advances that have been made in using miRNA as a biomarker for PDAC and its precursor lesions. PMID:26798434

  11. Colonic mucin synthesis is increased by sodium butyrate.

    PubMed

    Finnie, I A; Dwarakanath, A D; Taylor, B A; Rhodes, J M

    1995-01-01

    The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis.

  12. Adhesion Properties of Lactic Acid Bacteria on Intestinal Mucin

    PubMed Central

    Nishiyama, Keita; Sugiyama, Makoto; Mukai, Takao

    2016-01-01

    Lactic acid bacteria (LAB) are Gram-positive bacteria that are natural inhabitants of the gastrointestinal (GI) tracts of mammals, including humans. Since Mechnikov first proposed that yogurt could prevent intestinal putrefaction and aging, the beneficial effects of LAB have been widely demonstrated. The region between the duodenum and the terminal of the ileum is the primary region colonized by LAB, particularly the Lactobacillus species, and this region is covered by a mucus layer composed mainly of mucin-type glycoproteins. The mucus layer plays a role in protecting the intestinal epithelial cells against damage, but is also considered to be critical for the adhesion of Lactobacillus in the GI tract. Consequently, the adhesion exhibited by lactobacilli on mucin has attracted attention as one of the critical factors contributing to the persistent beneficial effects of Lactobacillus in a constantly changing intestinal environment. Thus, understanding the interactions between Lactobacillus and mucin is crucial for elucidating the survival strategies of LAB in the GI tract. This review highlights the properties of the interactions between Lactobacillus and mucin, while concomitantly considering the structure of the GI tract from a histochemical perspective. PMID:27681930

  13. Mupirocin-mucin agar for selective enumeration of Bifidobacterium bifidum.

    PubMed

    Pechar, Radko; Rada, Vojtech; Parafati, Lucia; Musilova, Sarka; Bunesova, Vera; Vlkova, Eva; Killer, Jiri; Mrazek, Jakub; Kmet, Vladimir; Svejstil, Roman

    2014-11-17

    Bifidobacterium bifidum is a bacterial species exclusively found in the human intestinal tract. This species is becoming increasingly popular as a probiotic organism added to lyophilized products. In this study, porcine mucin was used as the sole carbon source for the selective enumeration of B. bifidum in probiotic food additives. Thirty-six bifidobacterial strains were cultivated in broth with mucin. Only 13 strains of B. bifidum utilized the mucin to produce acids. B. bifidum was selectively enumerated in eight probiotic food supplements using agar (MM agar) containing mupirocin (100 mg/L) and mucin (20 g/L) as the sole carbon source. MM agar was fully selective if the B. bifidum species was presented together with Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and Bifidobacterium longum subsp. longum species and with lactic acid bacteria (lactobacilli, streptococci). Isolated strains of B. bifidum were identified using biochemical, PCR, MALDI-TOF procedures and 16S rRNA gene sequencing. The novel selective medium was also suitable for the isolation of B. bifidum strains from human fecal samples.

  14. Physical Properties of Human Whole Salivary Mucin:A Dynamic Light Scattering Study

    NASA Astrophysics Data System (ADS)

    Mahajan, Manish; Kumar, Vijay; Saraswat, Mayank; Yadav, Savita; Shukla, N. K.; Singh, T. P.

    2008-04-01

    Human salivary mucin, a primary mucous membrane coating glycoprotein forms the first line of defense against adverse environments, attributed to the complex formation between mucin subunits and non mucin species. Aim of the study was to emphasize the effect of pH, denaturants (guanidinum hydrochloride, urea) and detergents (CHAPS, TRITON X -100, SDS on human whole salivary mucin. Hydrodynamic size distribution was measured using DLS. It was observed that aggregation was due to increase in hydrophobic interactions, believed to be accomplished by unfolding of the protein core. Whereas, the detergents which solubilize the proteins by decreasing hydrophobicity lead to disaggregation of mucin into smaller fragments. Mucin subjected to tobacco extract and upon subsequent addition of nicotine was found to have a disaggregating effect on it, suggesting nicotine may be one of the factors responsible for the disaggregating effect of tobacco on mucin, an important carcinogenetic mechanism.

  15. Mucinous Carcinoma with Extensive Signet Ring Cell Differentiation: A Case Report

    PubMed Central

    Kim, Hye Min; Kim, Eun Kyung; Koo, Ja Seung

    2017-01-01

    Breast cancers that present with mucin include mucinous carcinoma and carcinoma with signet ring cell differentiation. The former shows extracellular mucin and the latter shows abundant intracellular mucin. Here, we report a case of breast cancer showing both extracellular mucin and extensive signet ring cell differentiation due to abundant intracellular mucin. Unlike mucinous carcinoma, this case had the features of high-grade nuclear pleomorphism, high mitotic index, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor-2 positivity, and ductal type with positivity for E-cadherin. In a case with signet ring cell differentiation, differential diagnosis with metastatic signet ring cell carcinoma of the stomach and colon is essential. In this case, the presence of accompanied ductal carcinoma in situ component and mammaglobin and gross cystic disease fluid protein-15 positivity were findings that suggested the breast as the origin. PMID:28316229

  16. Effect of dexamethasone and ACC on bacteria-induced mucin expression in human airway mucosa.

    PubMed

    Hauber, Hans-Peter; Goldmann, Torsten; Vollmer, Ekkehard; Wollenberg, Barbara; Zabel, Peter

    2007-11-01

    Gram-negative bacteria can stimulate mucin production, but excessive mucus supports bacterial infection and consequently leads to airway obstruction. Therefore, the effect of dexamethasone (DEX) and the antioxidant acetyl-cysteine (ACC) on bacteria-induced mucus expression was investigated. Explanted human airway mucosa and mucoepidermoid cells (Calu-3) were stimulated with lipopolysaccharide (LPS) or PAM3 (a synthetic lipoprotein). DEX or ACC were added to either LPS- or PAM3-stimulated airway mucosa or Calu-3 cells. Mucin mRNA expression (MUC5AC) and total mucus glycoconjugates (mucin protein) were quantified using real-time PCR and periodic acid Schiff staining. LPS and PAM3 significantly increased mucin expression in airway mucosa and Calu-3 cells (P < 0.05). DEX alone had no significant effect on mucin expression in airway mucosa or Calu-3 cells (P > 0.05). In contrast, DEX significantly reduced LPS- and PAM3-induced mucin expression in explanted mucosal tissue and mucin expression in Calu-3 cells (P < 0.05). In explanted human airway mucosa ACC alone significantly increased mucin expression (P < 0.05). In contrast, ACC significantly decreased LPS- and PAM3-induced mucin expression (P < 0.05). In Calu-3 cells ACC alone had no significant effect on mucin expression (P > 0.05). ACC decreased LPS- and PAM3-induced mucin expression, but this effect was not significant (P > 0.05). These data suggest that DEX can effectively reduce bacteria-induced mucin expression in the airways. ACC alone may increase mucin expression in noninfected mucosa, but it decreased bacteria-induced mucin expression. Further studies are warranted to evaluate whether the effect of DEX or ACC is clinically relevant.

  17. Protein-carbohydrate interactions between Lactobacillus salivarius and pig mucins.

    PubMed

    Iñiguez-Palomares, C; Jiménez-Flores, R; Vázquez-Moreno, L; Ramos-Clamont-Montfort, G; Acedo-Félix, E

    2011-10-01

    Adherence to the gastrointestinal tract is a key element desirable for many of the proposed beneficial health effects of probiotic bacteria. The aims of this study were to determine the amounts of adhesion of 3 Lactobacillus salivarius strains (Lb6, Lb9, and Lb10) to porcine small intestinal mucins and to determine whether adhesion is a function of lectin-like activities. Dot and Western blot assays were performed to investigate bacterial adhesion. Several carbohydrates and glycoproteins were evaluated to determine whether they interfered with adhesion of the Lactobacillus strains to intestinal mucins and to determine whether they had lectin-like activities. The Lb9 and Lb10 strains had greater association with piglet mucins than did those from 22- to 24-wk-old finishing pigs (P = 0.021 and 0.037, respectively), whereas the Lb6 strain adhered to both (P = 0.138). Western blot assays showed that bacterial adhesion detected piglet mucosa from the duodenum, jejunum, and ileum. In finishing pigs, the adhesion was variable throughout the gastrointestinal tract. Galactose and mannose diminished the interaction of the Lb9 and Lb10 strains in intestinal mucosa (P = 0.028 and 0.026, respectively), whereas pig gastric mucin reduced the adhesion of the Lb6 strain (P = 0.013). Adhesion of the Lb9 and Lb10 strains to intestinal mucosa was less after protease treatment (P = 0.023 and 0.018, respectively), which indicates that proteins are needed for the Lb9 and Lb10 strains to recognize mucin. The Lb6 strain also demonstrated diminished adhesion after periodate treatment (P = 0.038). From these results, we suggest that the nature of the bacterial lectin-like substance is a surface protein that loosely binds to the bacterial cell surface. All the tested strains adhered to specific targets in the small intestinal mucosa of piglets, and the bacteria had lectin-like proteins involved in this adhesion.

  18. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    PubMed

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  19. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma.

    PubMed

    Xu, Liyun; Huang, Yanyan; Tan, Linlin; Yu, Wei; Chen, Dongdong; Lu, ChangChang; He, Jianying; Wu, Guoqing; Liu, Xiaoguang; Zhang, Yongkui

    2015-12-01

    T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56+ cells (P<0.05) and CD3-CD56(dim) cells (P<0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P<0.05) or with tumor stage T3-T4 (P<0.05). Tim-3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size ≥3cm (P<0.05), or LNM (P<0.05) or with tumor stage T3-T4 (P<0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56+ NK cells and CD56(dim) NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P=0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-γ production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy.

  20. Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin

    PubMed Central

    2013-01-01

    Background Periampullary adenocarcinomas comprise pancreatic, distal bile duct, ampullary and duodenal adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. With steadily increasing numbers of pancreatoduodenectomies over the last decades, pathologists, surgeons and oncologists are more often confronted with the diagnosis of “other than pancreatic” periampullary cancers. The intestinal subtype of ampullary cancer has been shown to correlate with better prognosis. Methods Histological subtype and immunohistochemical staining pattern for CK7, CK20 and CDX2 were assessed for n = 198 cases of pancreatic ductal, distal bile duct, ampullary and duodenal adenocarcinoma with clinical follow-up. Routine pathological parameters were included in survival analysis performed with SPSS 20. Results In univariate analysis, intestinal subtype was associated with better survival in ampullary, pancreatic ductal and duodenal adenocarcinoma. The intestinal type of pancreatic ductal adenocarcinoma was not associated with intraductal papillary mucinous neoplasm and could not be reliably diagnosed by immunohistochemical staining pattern alone. Intestinal differentiation and lymph node ratio, but not tumor location were independent predictors of survival when all significant predictor variables from univariate analysis (grade, TNM stage, presence of precursor lesions, surgical margin status, perineural, vascular and lymphatic vessel invasion, CK7 and CDX2 staining pattern) were included in a Cox proportional hazards model. Conclusions Intestinal type differentiation and lymph node ratio but not tumor location are independent prognostic factors in pooled analysis of periampullary adenocarcinomas. We conclude that differentiation is more important than tumor location for prognostic stratification in periampullary adenocarcinomas. PMID:24053229

  1. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

    PubMed Central

    Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

    2015-01-01

    Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

  2. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  3. Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica.

    PubMed Central

    Chadee, K; Petri, W A; Innes, D J; Ravdin, J I

    1987-01-01

    Establishment of adherence by Entamoeba histolytica is mediated by a 170-kD Gal/GalNAc inhibitable lectin and is required for cytolysis and phagocytosis of mammalian target cells. We studied the biochemical mechanisms of the in vitro interaction between rat and human colonic mucins and axenic E. histolytica trophozoites. Crude mucus prevented amebic adherence to Chinese hamster ovary (CHO) cells by up to 70%. Purification of the colonic mucins by Sepharose 4B chromatography, nuclease digestion, and cesium chloride gradient centrifugation resulted in a 1,000-fold enrichment of the inhibitory mucins. Purified rat mucin inhibited amebic adherence to and cytolysis of homologous rat colonic epithelial cells. Oxidation and enzymatic cleavage of rat mucin Gal and GalNAc residues completely abrogated mucin inhibition of amebic adherence. The binding of rat 125I-mucin to amebae was galactose specific, saturable, reversible, and pH dependent. A monoclonal antibody specific for the 170-kD amebic Gal/GalNAc lectin completely inhibited the binding of rat 125I-mucin. Rat mucin bound to Affigel affinity purified the amebic lectin from conditioned medium. Colonic mucin glycoproteins act as an important host defense by binding to the parasite's adherence lectin, thus preventing amebic attachment to and cytolysis of host epithelial cells. Images PMID:2890655

  4. Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

    SciTech Connect

    Veluraja, K.; Vennila, K.N.; Umamakeshvari, K.; Jasmine, A.; Velmurugan, D.

    2011-03-25

    Research highlights: {yields} Techniques to get oriented mucin fibre. {yields} X-ray fibre diffraction pattern for mucin. {yields} Molecular modeling of mucin based on X-ray fibre diffraction pattern. -- Abstract: The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 A. The high intense d-spacing signal at 4.22 A is attributed to the antiparallel {beta}-sheet structure identified in the fraction of the homology modeled mucin molecule (amino acid residues 800-980) using Nidogen-Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 A reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.

  5. A procedure for Alcian blue staining of mucins on polyvinylidene difluoride membranes.

    PubMed

    Dong, Weijie; Matsuno, Yu-ki; Kameyama, Akihiko

    2012-10-16

    The isolation and characterization of mucins are critically important for obtaining insight into the molecular pathology of various diseases, including cancers and cystic fibrosis. Recently, we developed a novel membrane electrophoretic method, supported molecular matrix electrophoresis (SMME), which separates mucins on a polyvinylidene difluoride (PVDF) membrane impregnated with a hydrophilic polymer. Alcian blue staining is widely used to visualize mucopolysaccharides and acidic mucins on both blotted membranes and SMME membranes; however, this method cannot be used to stain mucins with a low acidic glycan content. Meanwhile, periodic acid-Schiff staining can selectively visualize glycoproteins, including mucins, but is incompatible with glycan analysis, which is indispensable for mucin characterizations. Here we describe a novel staining method, designated succinylation-Alcian blue staining, for visualizing mucins on a PVDF membrane. This method can visualize mucins regardless of the acidic residue content and shows a sensitivity 2-fold higher than that of Pro-Q Emerald 488, a fluorescent periodate Schiff-base stain. Furthermore, we demonstrate the compatibility of this novel staining procedure with glycan analysis using porcine gastric mucin as a model mucin.

  6. Species variation and spatial differences in mucin expression from corneal epithelial cells.

    PubMed

    Leonard, Brian C; Yañez-Soto, Bernardo; Raghunathan, Vijay Krishna; Abbott, Nicholas L; Murphy, Christopher J

    2016-11-01

    Mucins are large glycoproteins expressed by epithelial cells of both the conjunctiva and cornea, and principle components of the glycocalyx. They are thought to play an important role in determining the interactions between the cornea/conjunctiva and the overlying tear film. The purpose of this study was to characterize the membrane-associated corneal mucin expression pattern from multiple species commonly used in ophthalmic research and drug development to better define the biochemical attributes of the ocular surface. Humans, rhesus macaques and dogs were found to have a very similar pattern of mucin expression, with mucin 16 (MUC16) being the most prevalent mucin transcript. In contrast, the rabbit had a unique mucin expression pattern with all mucin transcripts expressed at relatively similar levels. To determine if there were spatial differences in expression, peripheral and central corneal epithelium were individually isolated and evaluated for mucin expression. In all species examined, MUC1, MUC4 and MUC16 had higher peripheral corneal expression when compared with central, which reached statistical significance in MUC1 (rhesus and dog). The data demonstrated variation in corneal epithelial membrane-associated mucin expression between species, with the rabbit having a distinct expression pattern. These differences may be reflective of the environment, pathogen exposure or tear film dynamics of the respective species. The species differences, as well as regional mucin expression patterns, characterized in this study further define the biochemical composition of the ocular surface and may play an important role in tear film stability.

  7. Periadnexal Mucin as an Additional Histopathologic Feature of Chronic Eczematous Dermatitis

    PubMed Central

    Lee, Noo Ri; Kim, Jae-Hong; Park, Hwa-Young; Yoon, Na Young

    2015-01-01

    Background Cutaneous mucinoses are a heterogeneous group of disorders characterized by an abnormal amount of mucin in the skin. However, the pathomechanism of an excessive mucin deposition in the skin is still unknown. Eczematous dermatitis is sub-classified histologically into acute, subacute, and chronic variants. The characteristic histopathologic findings for chronic eczema are variable. However, periadnexal mucin deposition is not known as a feature of chronic eczema. Objective To evaluate the presence of periadnexal mucin deposition in chronic eczematous dermatitis. Methods We analyzed the skin biopsy specimens from 36 patients who were pathologically diagnosed with chronic eczematous dermatitis. Alcian blue, colloidal iron, and periodic acid-Schiff stains were used to evaluate the mucin deposition in histologic sections. Two dermatologists and two dermatopathologists evaluated the degree of mucin deposition using a 4-point scale. Results Various amounts of mucin deposition were observed in the periadnexal area of patients who were diagnosed with chronic eczema. Mucin deposition was more visible after staining with mucin-specific stains. Evaluation of the staining analysis scores revealed that the staining intensities were significantly higher in patients with chronic eczema than age- and site-matched controls (normal, acute to subacute eczema, and psoriasis vulgaris). Conclusion Periadnexal mucin (secondary mucinoses) may be an additional finding of chronic eczematous dermatitis. PMID:25834351

  8. Overview of the clinical problem: facts and current issues of mucinous cystic neoplasms of the pancreas.

    PubMed

    Jeurnink, S M; Vleggaar, F P; Siersema, P D

    2008-11-01

    Pancreatic cystic lesions are uncommon and consist of pseudocysts, congenital cysts and cystic neoplasms including mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms. Mucinous cystic neoplasms are large septated cysts without connection to the ductal system, characterised by the presence of thick-walled ovarian-type stroma and mucin. They occur predominantly in women and often are malignant. Therefore, surgical resection is recommended. Intraductal papillary mucinous neoplasms are neoplasms with tall, columnar, mucin-containing epithelium involving the main pancreatic ducts or major side branches. Intraductal papillary mucinous neoplasms occur in men and women in their 60s and 70s and may differentiate into malignant neoplasms. Therefore, surgical resection is mandatory. Serous cystic neoplasms appear as multiple cysts lined with cubic flat epithelium containing glycogen-rich cells with clear cytoplasm. They mainly occur in women in their 50s and are generally benign. Therefore, a conservative approach is recommended. As both mucinous cystic neoplasm and intraductal papillary mucinous neoplasms have a high malignant potential, it is important to differentiate between the various pancreatic cystic lesions. Several imaging techniques and tumour markers have been evaluated. Nonetheless, definitive guidelines to differentiate between serous cystic neoplasms, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are still poorly defined. A number of management issues regarding these neoplasms are still under debate, for example which imaging technique to use, differentiation between malignant or benign lesions and the preferred treatment modality for each pancreatic cystic neoplasm. Further research may lead to a definitive guideline for the diagnosis and treatment of mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms.

  9. Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

    PubMed Central

    Puppa, G; Maisonneuve, P; Sonzogni, A; Masullo, M; Chiappa, A; Valerio, M; Zampino, M G; Franceschetti, I; Capelli, P; Chilosi, M; Menestrina, F; Viale, G; Pelosi, G

    2007-01-01

    Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas. PMID:17375048

  10. Rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma: a case report and review of literature

    PubMed Central

    Chen, Hui; Luo, Qiuping; Liu, Shaoyan; Xiong, Hanzhen; Jiang, Qingping

    2015-01-01

    Endometriosis involving intestinal mucosa is relatively uncommon. It poses a diagnostic challenge for clinicians and pathologists. We herein report a case of colonoscopic specimen revealing rectal mucosal endometriosis. A 39-year-old woman complained of red rectal bleeding and intermittent abdominal pain. Colonoscopic examination showed a rectal mass with ulceration and circum wall involvement. Biopsy was processed in the suspicious of carcinoma. Morphologically, irregular glands replaced residual colorectal ones, displayed mucin depletion, nuclear stratification and subtile subnuclear vacuoles. The stroma was full of spindle cells with abundant pink cytoplasm and unclear boundary. Due to subjectively interpreting as dysplastic glands in desmoplastic setting, primary rectal adenocarcinoma was firstly raised. Immunohistochemically, CK7, ER and CD10 identified the essence of ectopic endometrium. CK20 and CDX2 highlighted residual glands. In case of misdiagnosis, any pathologists should be aware of intestinal endometriosis for each female’s colorectal biopsy, especially for that morphology not typical for primary adenocarcinoma or endometriosis. Reading slides carefully combined with a panel of immunomarkers would solve the pitfall. PMID:26191316

  11. Uncommon features of surgically resected ALK-positive cavitary lung adenocarcinoma: a case report.

    PubMed

    Takamori, Shinkichi; Yamaguchi, Masafumi; Taguchi, Kenichi; Edagawa, Makoto; Shimamatsu, Shinichiro; Toyozawa, Ryo; Nosaki, Kaname; Hirai, Fumihiko; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2017-12-01

    Some features found on chest computed tomography (CT), such as central tumor location, large pleural effusion, and the absence of a pleural tail, and a patient age of less than 60 years, have been suggested to be useful in predicting anaplastic lymphoma kinase (ALK) rearrangement in patients with non-small cell lung cancer (NSCLC).A 68-year-old female patient with a history of gynecological treatment was found to have a cavitary mass in the right lower lobe on an annual chest roentgenogram. The tumor was located in the peripheral area with a pleural tail showing no pleural effusion. In addition, two pure ground-glass-opacity nodules (p-GGNs) in the right upper lobe of the lung were detected on consecutive chest CT scans. The patient underwent right lower lobectomy, partial resection of the right upper lobe, and hilar mediastinal lymph node dissection for complete resection of each tumor. The pathological diagnosis was invasive mucinous adenocarcinoma with signet-ring cells for the cavitary mass in the right lower lobe and invasive adenocarcinoma for the rest of the p-GGNs; subcarinal lymph node metastasis was also detected. The ALK rearrangement was detected by fluorescence in situ hybridization from the cavitary mass. The patient underwent four cycles of cisplatin and vinorelbine chemotherapy as standard adjuvant chemotherapy for pStage III NSCLC. The ALK fusion gene status of NSCLC with atypical CT features should also be investigated.

  12. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  13. Smoking Is Not Associated with Severe Dysplasia or Invasive Carcinoma in Resected Intraductal Papillary Mucinous Neoplasms

    PubMed Central

    Rezaee, Neda; Khalifian, Saami; Cameron, John L.; Pawlik, Timothy M.; Hruban, Ralph H.; Fishman, Elliot K.; Makary, Martin A.; Lennon, Anne Marie; Wolfgang, Christopher L.; Weiss, Matthew J.

    2015-01-01

    Introduction Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are precursor lesions that progress to invasive cancer through progressively worsening dysplasia. Although smoking is an established risk factor for pancreatic adenocarcinoma, potential associations with IPMN grade of dysplasia remain unclear. Methods Pancreatic resections for IPMN from 1995 to 2013 were retrospectively reviewed. A total of 446 patients in which the smoking status was documented were identified. Results Smoking history was positive in 47 % of patients. Of smokers, 50 % had branch-duct, 14 % had main-duct, and 36 % had mixed-type IPMN. Patients with main-duct IPMN were more commonly smokers (65 %), compared to smoking history in 46 % with mixed and 44 % with branch-duct IPMN (p=0.03). High-grade dysplasia occurred in 25 % of smokers and 21 % of nonsmokers (p=0.32), and invasive carcinoma in 25 % of smokers and 25 % nonsmokers (p= 0.95). On multivariate analysis, duct size was independently associated with high-grade dysplasia (OR=3.17, 95 %CI= 1.79–5.64, p<0.001). Presence of mural nodules (OR=3.34, 95 %CI=1.82–6.12, p<0.001), duct size (OR=3.87, 95 %CI=2.21–6.75, p<0.001), and symptoms (OR=7.10, 95 %CI=3.80–13.08, p<0.001), but not smoking history (OR=1.10, 95 %CI=0.64–1.88, p=0.73), were independent predictors of invasive carcinoma. Median overall survival was 70 months for smokers and 88 months for nonsmokers (p=0.68). Conclusion Positive smoking history correlated with duct type classification but does not appear to be a risk factor for harboring high-grade dysplasia or invasive carcinoma in IPMNs. PMID:25477314

  14. MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer

    PubMed Central

    Eyking, Annette; Reis, Henning; Frank, Magdalena; Gerken, Guido; Schmid, Kurt W.; Cario, Elke

    2016-01-01

    Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion

  15. Epithelial-to-mesenchymal transition in a fistula-associated anal adenocarcinoma in a patient with long-standing Crohn's disease.

    PubMed

    Scharl, Michael; Frei, Pascal; Frei, Sandra M; Biedermann, Luc; Weber, Achim; Rogler, Gerhard

    2014-01-01

    Anal adenocarcinomas arising from perianal fistulae represent a rare complication in Crohn's disease (CD) patients. We have previously demonstrated the involvement of an epithelial-to-mesenchymal transition (EMT) in the pathogenesis of CD-associated fistulae. Although EMT has also been implicated in the development of colorectal and anal carcinoma, the molecular link from fistula to carcinoma is unclear. We present a case of a 48-year-old White woman who developed a mucinous anal adenocarcinoma originating from a perianal, CD-associated fistula 24 years after being diagnosed with CD. To characterize the expression of EMT-associated molecules in fistula and carcinoma tissue, immunohistochemical analysis for Snail1, Slug, β-catenin and E-cadherin was performed. A mucinous anal adenocarcinoma developed on a perianal fistula in a patient with long-standing CD. After neoadjuvant radiochemotherapy, the fistula-associated tumour was resected and the patient is presently in remission. Using immunohistochemical analysis, we detected a remarkable staining of the Slug transcription factor in transitional cells lining the fistula tract. This observation is unique to this 'carcinoma'-fistula: we had previously shown Slug expression in cells surrounding the fistula tract but not in transitional cells. Expression of Snail1, β-catenin and E-cadherin in this case was comparable with our previous findings. We describe a rare case of a CD fistula-associated adenocarcinoma within an area of squamous epithelium of the perianal area and an unusual expression pattern of EMT markers in this fistula. This case seems to underline the relevance of our previous findings demonstrating that EMT plays an important role for fistula pathogenesis and likely carcinogenesis in CD patients.

  16. Unstable giant gravitons

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Smolic, Jelena; Smolic, Milena

    2006-03-15

    We find giant graviton solutions in Frolov's three parameter generalization of the Lunin-Maldacena background. The background we study has {gamma}-tilde{sub 1}=0 and {gamma}-tilde{sub 2}={gamma}-tilde{sub 3}={gamma}-tilde. This class of backgrounds provides a nonsupersymmetric example of the gauge theory/gravity correspondence that can be tested quantitatively, as recently shown by Frolov, Roiban, and Tseytlin. The giant graviton solutions we find have a greater energy than the point gravitons, making them unstable states. Despite this, we find striking quantitative agreement between the gauge theory and gravity descriptions of open strings attached to the giant.

  17. Primary retroperitoneal mucinous cystadenoma with sarcoma-like mural nodule

    PubMed Central

    Bakker, R. F. R.; Stoot, J. H. M. B.; Blok, P.

    2007-01-01

    Primary retroperitoneal cystadenomas are extremely rare. This is the first report in literature to describe a primary retroperitoneal cystadenoma with a sarcoma-like mural nodule. A 45-year-old woman complained of a left-sided abdominal mass. A computed tomography scan revealed a cystic mass with a mural nodule, which seemed to originate from the tail of the pancreas. At laparotomy the cyst was not adhered to the pancreas but localized retroperitoneally. Histologic examination showed a mucinous cystadenoma with only foci of borderline malignancy with a mural “sarcoma-like” nodule. In view of the surgical and histopathological findings, the mucinous cystadenoma was regarded as primary retroperitoneal. This case demonstrates that in the era of radiological preoperative refinement, pathological diagnosis remains of utmost importance, especially for rare cases. PMID:17690906

  18. Endocrine mucin-producing sweat gland carcinoma of the eyelid.

    PubMed

    Collinson, Anne C; Sun, Michelle T; James, Craig; Huilgol, Shyamala C; Selva, Dinesh

    2015-12-01

    An elderly woman was incidentally noted to have a nodular mass on the upper eyelid, whilst under investigation for cataracts. Punch biopsy of this presumed basal cell carcinoma revealed it to be endocrine mucin-producing sweat gland carcinoma (EMPSGC). The tumour extended to the deep dermal layer and comprised solid nests with foci of cystic and papillary change, and additional cytoplasmic and focal extracellular mucin deposits. Immunohistochemistry confirmed epithelial lineage and neuroendocrine differentiation, and adjacent tissue invasion. The tumour was excised completely with Mohs micrographic surgery with no recurrence after 8 months. EMPSGC is a low-grade sweat gland carcinoma with variable neuroendocrine differentiation, a solid, papillary, or cystic growth pattern, and a predilection for the eyelid of elderly women [Am J Surg Pathol 29:1330-1339, 2005]. There have been 54 previously documented cases of EMPSCG. We report an additional case and review the literature.

  19. Enzymatically active biomimetic micropropellers for the penetration of mucin gels

    PubMed Central

    Walker, Debora; Käsdorf, Benjamin T.; Jeong, Hyeon-Ho; Lieleg, Oliver; Fischer, Peer

    2015-01-01

    In the body, mucus provides an important defense mechanism by limiting the penetration of pathogens. It is therefore also a major obstacle for the efficient delivery of particle-based drug carriers. The acidic stomach lining in particular is difficult to overcome because mucin glycoproteins form viscoelastic gels under acidic conditions. The bacterium Helicobacter pylori has developed a strategy to overcome the mucus barrier by producing the enzyme urease, which locally raises the pH and consequently liquefies the mucus. This allows the bacteria to swim through mucus and to reach the epithelial surface. We present an artificial system of reactive magnetic micropropellers that mimic this strategy to move through gastric mucin gels by making use of surface-immobilized urease. The results demonstrate the validity of this biomimetic approach to penetrate biological gels, and show that externally propelled microstructures can actively and reversibly manipulate the physical state of their surroundings, suggesting that such particles could potentially penetrate native mucus. PMID:26824056

  20. Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge

    PubMed Central

    Salama, Samih; Gohla, Gabriella; Alowami, Salem

    2017-01-01

    Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production. Since it was first described by Flieder et al. in 1997, less than 60 cases have been reported in literature. We describe the morphological and immunohistochemical features of another case with a review of the common histological differential diagnoses and emphasize the salient features that help distinguish this rare neoplasm. PMID:28299221

  1. Synthetic Oral Mucin Mimic from Polymer Micelle Networks

    PubMed Central

    2015-01-01

    Mucin networks are formed in the oral cavity by complexation of glycoproteins with other salivary proteins, yielding a hydrated lubricating barrier. The function of these networks is linked to their structural, chemical, and mechanical properties. Yet, as these properties are interdependent, it is difficult to tease out their relative importance. Here, we demonstrate the ability to recreate the fibrous like network through a series of complementary rinses of polymeric worm-like micelles, resulting in a 3-dimensional (3D) porous network that can be deposited layer-by-layer onto any surface. In this work, stability, structure, and microbial capture capabilities were evaluated as a function of network properties. It was found that network structure alone was sufficient for bacterial capture, even with networks composed of the adhesion-resistant polymer, poly(ethylene glycol). The synthetic networks provide an excellent, yet simple, means of independently characterizing mucin network properties (e.g., surface chemistry, stiffness, and pore size). PMID:24992241

  2. Molecular pathogenesis of intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Thosani, Nirav; Dasari, Chandra S; Bhutani, Manoop S; Raimondo, Massimo; Guha, Sushovan

    2010-11-01

    Over the last 3 decades, there have been substantial improvements in diagnostic imaging and sampling techniques to evaluate pancreatic diseases. The modern technology has helped us to recognize premalignant conditions of pancreas including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMNs). Differentiation between benign and malignant lesions and early detection of any malignant transformation in premalignant lesion are extremely important for further management decisions. Diagnostic cytology has limited sensitivity to further differentiate between benign, premalignant, and malignant lesions of the pancreas. There is limited information about the epidemiological risk factors and molecular mechanisms leading to development and further progression to malignancy of IPMNs. Several studies have shown that pancreatic juice and pancreatic tissue from the lesion can be tested for molecular markers including K-ras, p53, and p16 to differentiate between cancer and chronic inflammatory process. We review cellular signaling pathways that contribute to pathogenesis of IPMNs of the pancreas to further identify potential biomarkers and molecular targets.

  3. CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

    PubMed Central

    Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

    2012-01-01

    Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

  4. [An unusual secondary localization of bronchial adenocarcinoma].

    PubMed

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J

    1993-01-01

    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  5. [Mesocolic excision for colonic adenocarcinoma].

    PubMed

    Debove, Clotilde; Lefèvre, Jérémie H; Parc, Yann

    2017-02-01

    On the same principle than total mesorectal excision in rectal cancer, the effect of complete mesocolic excision on short and long-term outcomes is actually evaluated for colonic adenocarcinoma. This method, usually performed for left colectomy, offers a surgical specimen of higher quality, with a larger number of lymph nodes harvested. For right colectomy, surgical specifications make it less common complete mesocolic excision and conventional surgery offer comparable outcomes, as regards to postoperative morbidity and mortality rates. No differences are identified between laparoscopic and open surgery. On oncologic outcomes, only two studies report a higher free-disease survival after complete mesocolic excision. Then, there is evidence that complete mesocolic excision offers a higher rate of specimen with extensive lymph node resection, without increased morbidity rate. However, there is limited evidence that it leads to improve long-term oncological outcomes.

  6. Mucins help to avoid alloreactivity at the maternal fetal interface.

    PubMed

    Redzovic, Arnela; Laskarin, Gordana; Dominovic, Marin; Haller, Herman; Rukavina, Daniel

    2013-01-01

    During gestation, many different mechanisms act to render the maternal immune system tolerant to semi-allogeneic trophoblast cells of foetal origin, including those mediated via mucins that are expressed during the peri-implantation period in the uterus. Tumour- associated glycoprotein-72 (TAG-72) enhances the already established tolerogenic features of decidual dendritic cells with the inability to progress towards Th1 immune orientation due to lowered interferon (IFN)- γ and interleukin (IL)-15 expression. Mucine 1 (Muc 1) supports alternative activation of decidual macrophages, restricts the proliferation of decidual regulatory CD56(+) bright natural killer (NK) cells, and downregulates their cytotoxic potential, including cytotoxic mediator protein expression. Removing TAG-72 and Muc 1 from the eutopic implantation site likely contributes to better control of trophoblast invasion by T cells and NK cells and appears to have important immunologic advantages for successful implantation, in addition to mechanical advantages. However, these processes may lead to uncontrolled trophoblast growth after implantation, inefficient defence against infection or tumours, and elimination of unwanted immunocompetent cells at the maternal-foetal interface. The use of mucins by tumour cells to affect the local microenvironment in order to avoid the host immune response and to promote local tumour growth, invasion, and metastasis confirms this postulation.

  7. Mucins Help to Avoid Alloreactivity at the Maternal Fetal Interface

    PubMed Central

    Redzovic, Arnela; Laskarin, Gordana; Haller, Herman

    2013-01-01

    During gestation, many different mechanisms act to render the maternal immune system tolerant to semi-allogeneic trophoblast cells of foetal origin, including those mediated via mucins that are expressed during the peri-implantation period in the uterus. Tumour- associated glycoprotein-72 (TAG-72) enhances the already established tolerogenic features of decidual dendritic cells with the inability to progress towards Th1 immune orientation due to lowered interferon (IFN)-γ and interleukin (IL)-15 expression. Mucine 1 (Muc 1) supports alternative activation of decidual macrophages, restricts the proliferation of decidual regulatory CD56+ bright natural killer (NK) cells, and downregulates their cytotoxic potential, including cytotoxic mediator protein expression. Removing TAG-72 and Muc 1 from the eutopic implantation site likely contributes to better control of trophoblast invasion by T cells and NK cells and appears to have important immunologic advantages for successful implantation, in addition to mechanical advantages. However, these processes may lead to uncontrolled trophoblast growth after implantation, inefficient defence against infection or tumours, and elimination of unwanted immunocompetent cells at the maternal-foetal interface. The use of mucins by tumour cells to affect the local microenvironment in order to avoid the host immune response and to promote local tumour growth, invasion, and metastasis confirms this postulation. PMID:23864879

  8. Salivary Mucins Protect Surfaces from Colonization by Cariogenic Bacteria

    PubMed Central

    Frenkel, Erica Shapiro

    2014-01-01

    Understanding how the body's natural defenses function to protect the oral cavity from the myriad of bacteria that colonize its surfaces is an ongoing topic of research that can lead to breakthroughs in treatment and prevention. One key defense mechanism on all moist epithelial linings, such as the mouth, gastrointestinal tract, and lungs, is a layer of thick, well-hydrated mucus. The main gel-forming components of mucus are mucins, large glycoproteins that play a key role in host defense. This study focuses on elucidating the connection between MUC5B salivary mucins and dental caries, one of the most common oral diseases. Dental caries is predominantly caused by Streptococcus mutans attachment and biofilm formation on the tooth surface. Once S. mutans attaches to the tooth, it produces organic acids as metabolic by-products that dissolve tooth enamel, leading to cavity formation. We utilize CFU counts and fluorescence microscopy to quantitatively show that S. mutans attachment and biofilm formation are most robust in the presence of sucrose and that aqueous solutions of purified human MUC5B protect surfaces by acting as an antibiofouling agent in the presence of sucrose. In addition, we find that MUC5B does not alter S. mutans growth and decreases surface attachment and biofilm formation by maintaining S. mutans in the planktonic form. These insights point to the importance of salivary mucins in oral health and lead to a better understanding of how MUC5B could play a role in cavity prevention or diagnosis. PMID:25344244

  9. Diffusion through Pig Gastric Mucin: Effect of Relative Humidity

    PubMed Central

    Runnsjö, Anna; Dabkowska, Aleksandra P.; Sparr, Emma; Kocherbitov, Vitaly; Arnebrant, Thomas; Engblom, Johan

    2016-01-01

    Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals. PMID:27336158

  10. Tea Derived Galloylated Polyphenols Cross-Link Purified Gastrointestinal Mucins

    PubMed Central

    Georgiades, Pantelis; Pudney, Paul D. A.; Rogers, Sarah; Thornton, David J.; Waigh, Thomas A.

    2014-01-01

    Polyphenols derived from tea are thought to be important for human health. We show using a combination of particle tracking microrheology and small-angle neutron scattering that polyphenols acts as cross-linkers for purified gastrointestinal mucin, derived from the stomach and the duodenum. Both naturally derived purified polyphenols, and green and black tea extracts are shown to act as cross-linkers. The main active cross-linking component is found to be the galloylated forms of catechins. The viscosity, elasticity and relaxation time of the mucin solutions experience an order of magnitude change in value upon addition of the polyphenol cross-linkers. Similarly small-angle neutron scattering experiments demonstrate a sol-gel transition with the addition of polyphenols, with a large increase in the scattering at low angles, which is attributed to the formation of large scale (>10 nm) heterogeneities during gelation. Cross-linking of mucins by polyphenols is thus expected to have an impact on the physicochemical environment of both the stomach and duodenum; polyphenols are expected to modulate the barrier properties of mucus, nutrient absorption through mucus and the viscoelastic microenvironments of intestinal bacteria. PMID:25162539

  11. Histochemical profiles of mucins in the tracheal epithelium during the posthatching period of Japanese quail.

    PubMed

    Alan, Emel; Liman, Narin

    2010-01-01

    Mucus normally protects the airway epithelium from dehydration and inhaled infectious agents and possibly toxic substances. Two components of mucus, mucin and water play major roles in the elimination of inhaled foreign material. Mucins are large carbohydrates rich glycoprotein. The objective of the present study was to determine the histochemical changes in mucin pattern of the goblet cells and intraepithelial glands of the trachea in quails during the post-hatching period using specific various staining procedures for complex carbohydrates (Periodic acid Schiff, Alcian blue-Periodic acid Schiff (pH 2.5), Aldehyde fuchsin-Alcian blue (pH 2.5), High-iron diamine-Alcian blue (pH 2.5), Periodic acid-Phenylhydrazine-Schiff). The intraepithelial alveolar glands were present at hatching and their numbers increased with the advance of age. In quail of all ages, the histochemical reactions revealed that the goblet cells and mucous cells of intraepithelial glands contained the mucins with vicinal diol groups, neutral mucin, sialomucin and sulphomucin. In all ages studied, the tracheal epithelium contained three distinct types of goblet or mucous cells producing neutral-, acid- and mixture of neutral- and acid mucins. In 1 day old, the majority of the goblet cells and gland cells contained neutral mucin or a mixture of neutral- and acid mucins, while the proportion of only acid mucin-producing cells was few. The majority of acidic mucins consisted of sulphomucin. The sialomucin-containing cells were only a few. After day 14, it was seen that the content of sialomucin in the epithelium became more diffuse toward adulthood. In conclusion, the content of mucin of tracheal epithelium was variable depending on the ages during the post-hatching period. These changes in mucin dynamics could affect the protective functions against pathogens and toxins of the tracheal epithelium.

  12. Palliative Surgical Approach in Advanced Nonresponsive Mucinous Ovarian Cancer: A Rare Case Report

    PubMed Central

    Agarwal, Manika; Kumar, Ritesh; Topno, Noor; Mishra, Shweta; Dhirasaria, Ashish; Singh, A Santa

    2016-01-01

    Advanced mucinous ovarian cancer is a separate entity and has different biological behaviour. There is a wide range of therapeutic challenges and dilemmas in the management of these patients. The authors present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who had poor response to standard neoadjuvant chemotherapy. This case is highlighted to emphasize the challenges in the decision making for the management of advanced mucinous ovarian cancer. PMID:27162429

  13. A Rare Renal Epithelial Tumor: Mucinous Cystadenocarcinoma Case Report and Review of the Literature

    PubMed Central

    Tepeler, Abdulkadir; Erdem, Mehmet Remzi; Kurt, Omer; Topaktas, Ramazan; Kilicaslan, Isin; Armağan, Abdullah; Önol, Şinasi Yavuz

    2011-01-01

    Primary renal mucinous cystadenocarcinoma is a very rare lesion of kidney which originates from the metaplasia of the renal pelvic uroepithelium. Only one case with primary mucinous cystadenocarcinoma has been reported in the English literature. We report second case of mucinous cystadenocarcinoma which was radiologically classified as type-IIF Bosniak cyst in peripheral localization. We aimed to present this extreme and unusual entity with its radiological, surgical, and pathologic aspects under the light of literature. PMID:22110514

  14. Growth in and breakdown of purified rabbit small intestinal mucin by Yersinia enterocolitica.

    PubMed Central

    Mantle, M; Rombough, C

    1993-01-01

    The mucus lining of the gastrointestinal tract serves as a protective barrier over the epithelial surface that must be crossed by invading bacteria seeking entry into the mucosa. The gel-forming component of mucus is mucin, a large polymeric glycoprotein. The present study examined the growth of Yersinia enterocolitica (with and without its virulence plasmid) in purified rabbit small intestinal mucin and the ability of bacteria to degrade mucin. Both virulent and nonvirulent organisms showed enhanced growth in mucin-supplemented media compared with unsupplemented media, but only at 37 degrees C and not at 25 degrees C. The effects of mucin were not specific because medium supplemented with bovine serum albumin also enhanced bacterial growth at 37 degrees C. Purified mucin was broken down into lower-molecular-weight components (assessed by monitoring its elution profile on a Sepharose CL-2B column) by plasmid-bearing Y. enterocolitica but not by plasmid-cured organisms. Culturing virulent Y. enterocolitica at 25 degrees C completely suppressed its capacity to degrade mucin, suggesting that this activity depends on plasmid expression. These results were confirmed in similar studies with purified rabbit colonic mucin. Mucin-degrading activity could be demonstrated in spent culture media from virulent Y. enterocolitica incubated at 37 degrees C but not in bacterial membrane preparations. Changes in the elution profiles of small intestinal and colonic mucins exposed to plasmid-bearing Y. enterocolitica at 37 degrees C were consistent with proteolytic depolymerization. The ability to grow well in mucin may help Y. enterocolitica to colonize the intestine, while the production of a mucin-degrading enzyme(s) by plasmid-bearing organisms may assist pathogenic strains to solubilize and penetrate the mucus gel layer. PMID:8406802

  15. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins.

    PubMed

    Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille

    2016-06-14

    Mucins, the heavily-glycosylated proteins lining mucosal surfaces, have evolved as a key component of innate defense by protecting the epithelium against invading pathogens. The main role of these macromolecules is to facilitate particle trapping and clearance while promoting lubrication of the mucosa. During protein synthesis, mucins undergo intense O-glycosylation and multimerization, which dramatically increase the mass and size of these molecules. These post-translational modifications are critical for the viscoelastic properties of mucus. As a result of the complex biochemical and biophysical nature of these molecules, working with mucins provides many challenges that cannot be overcome by conventional protein analysis methods. For instance, their high-molecular-weight prevents electrophoretic migration via regular polyacrylamide gels and their sticky nature causes adhesion to experimental tubing. However, investigating the role of mucins in health (e.g., maintaining mucosal integrity) and disease (e.g., hyperconcentration, mucostasis, cancer) has recently gained interest and mucins are being investigated as a therapeutic target. A better understanding of the production and function of mucin macromolecules may lead to novel pharmaceutical approaches, e.g., inhibitors of mucin granule exocytosis and/or mucolytic agents. Therefore, consistent and reliable protocols to investigate mucin biology are critical for scientific advancement. Here, we describe conventional methods to separate mucin macromolecules by electrophoresis using an agarose gel, transfer protein into nitrocellulose membrane, and detect signal with mucin-specific antibodies as well as infrared fluorescent gel reader. These techniques are widely applicable to determine mucin quantitation, multimerization and to test the effects of pharmacological compounds on mucins.

  16. The Next Giant Step

    NASA Video Gallery

    Artist Robert McCall painted "The Next Giant Step" in 1979 to commemorate the heroism and courage of spaceflight pioneers. Located in the lobby of Johnson's building 2, the mural depicts America's ...

  17. The Giant Cell.

    ERIC Educational Resources Information Center

    Stockdale, Dennis

    1998-01-01

    Provides directions for the construction of giant plastic cells, including details for building and installing the organelles. Also contains instructions for preparing the ribosomes, nucleolus, nucleus, and mitochondria. (DDR)

  18. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

    PubMed Central

    Posey, Avery D.; Schwab, Robert D.; Boesteanu, Alina C.; Steentoft, Catharina; Mandel, Ulla; Engels, Boris; Stone, Jennifer D.; Madsen, Thomas D.; Schreiber, Karin; Haines, Kathleen M.; Cogdill, Alexandria P.; Chen, Taylor J.; Song, Decheng; Scholler, John; Kranz, David M.; Feldman, Michael D.; Young, Regina; Keith, Brian; Schreiber, Hans; Clausen, Henrik; Johnson, Laura A.; June, Carl H.

    2017-01-01

    SUMMARY Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells. PMID:27332733

  19. The effect of the space flight environment on mucin production in the mouse uterine tube

    NASA Astrophysics Data System (ADS)

    Svalina, Gorica; Forsman, Allan D.

    2013-06-01

    Numerous studies have indicated that the microgravity environment of space has harmful effects on several tissues throughout the body. Although this phenomenon is well documented, research in this area is still in its relative infancy. This study investigates the effects of space flight on mucin production of the uterine tubes of mice. This study examined the epithelium of the uterine tubes from female mice that were flown on the space shuttle Endeavour for 13 days in August, 2007 and their concomitant controls. The tissue was qualitatively analyzed for the type of mucin produced, i.e., acidic, neutral, acidic/neutral mixture. Further, the tissue was quantitatively analyzed for the amounts of mucins produced by measuring the thickness of the mucin layer for each region of the uterine tube: isthmus, ampulla, and infundibulum. One way ANOVA tests were used to compare mucin thickness between all three sets of animals. Results indicate similar but not identical results between the three regions of the uterine tube. The Baseline tissue had the thickest mucin layer regardless of treatment group. In the ampulla the mucin layer was the thinnest in the Flight tissue, followed by the Ground Control, with the Baseline being the thickest. Analysis of the mucin layer of the infundibulum of the three treatment groups indicated no difference in its thickness between the three regions of the uterine tube. These results indicate a trend toward thinning of the mucin layer of the uterine tube in space flight, but also indicate an influence by the housing environment.

  20. Methods to Assess the Direct Interaction of C. jejuni with Mucins.

    PubMed

    Clyne, Marguerite; Duggan, Gina; Naughton, Julie; Bourke, Billy

    2017-01-01

    Studies of the interaction of bacteria with mucus-secreting cells can be complemented at a more mechanistic level by exploring the interaction of bacteria with purified mucins. Here we describe a far Western blotting approach to show how C. jejuni proteins separated by SDS PAGE and transferred to a membrane or slot blotted directly onto a membrane can be probed using biotinylated mucin. In addition we describe the use of novel mucin microarrays to assess bacterial interactions with mucins in a high-throughput manner.

  1. Profile of the intermolecular forces governing the interaction of drugs with mucin.

    PubMed

    Caron, Giulia; Visentin, Sonja; Pontremoli, Carlotta; Ermondi, Giuseppe

    2015-07-05

    The study highlights the balance of the intermolecular forces governing the interaction between drugs and mucin. The interaction strength is expressed as a retention factor k (data retrieved from the literature (Gargano et al., 2014)) obtained by a new bio-affinity chromatographic method in which the stationary phase is based on covalently immobilized mucin (porcine gastric mucin, PGM). A quantitative structure-property relationship (QSPR) between logk and 82 VolSurf+ descriptors was established and mechanistically interpreted. Results evidence that all blocks contribute similarly to the model; moreover, hydrogen bonding donor (HBD) properties of solutes favor the interaction with mucin; and thus, support their detrimental role on drug permeability.

  2. Ocular surface mucins and local inflammation--studies in genetically modified mouse lines.

    PubMed

    Shirai, Kumi; Saika, Shizuya

    2015-12-17

    Mucins locate to the apical surfaces of all wet-surfaced epithelia including ocular surface. The functions of the mucins include anti-adhesive, lubrication, water retention, allergens and pathogen barrier function. Ocular surface pathologies, i.e. dry eye syndrome or allergic conjunctivitis, are reportedly associated with alteration of expression pattern of mucin components. Recent investigations indicated anti-bacterial adhesion or anti-inflammatory effects of members of mucins in non-ocular tissues, i.e., gastrointestinal tracts or airway tissues, by using genetically modified mouse lines that lacks an expression of a mucin member. However, examination of ocular phenotypes of each of mucin gene-ablated mouse lines has not yet fully performed. Muc16-deficient mouse is associated with spontaneous subclinical inflammation in conjunctiva. The article reviews the roles of mucin members in modulation of local inflammation in mucous membrane tissues and phenotype of mouse lines with the loss of a mucin gene. Analysis of ocular surface of mucin-gene related mutant mouse lines are to be further performed.

  3. Mucin-bacterial interactions in the human oral cavity and digestive tract

    PubMed Central

    van Passel, Mark WJ; van de Bovenkamp, Jeroen HB; Schipper, Raymond G; de Vos, Willem M; Dekker, Jan

    2010-01-01

    Mucins are a family of heavily glycosylated proteins that are the major organic components of the mucus layer, the protective layer covering the epithelial cells in many human and animal organs, including the entire gastro-intestinal tract. Microbes that can associate with mucins benefit from this interaction since they can get available nutrients, experience physico-chemical protection and adhere, resulting in increased residence time. Mucin-degrading microorganisms, which often are found in consortia, have not been extensively characterized as mucins are high molecular weight glycoproteins that are hard to study because of their size, complexity and heterogeneity. The purpose of this review is to discuss how advances in mucus and mucin research, and insight in the microbial ecology promoted our understanding of mucin degradation. Recent insight is presented in mucin structure and organization, the microorganisms known to use mucin as growth substrate, with a specific attention on Akkermansia muciniphila, and the molecular basis of microbial mucin degradation owing to availability of genome sequences. PMID:21327032

  4. Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer

    PubMed Central

    Macha, Muzafar A.; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K.; Jain, Maneesh

    2015-01-01

    Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. PMID:25624117

  5. Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure.

    PubMed

    Henderson, Ashley G; Ehre, Camille; Button, Brian; Abdullah, Lubna H; Cai, Li-Heng; Leigh, Margaret W; DeMaria, Genevieve C; Matsui, Hiro; Donaldson, Scott H; Davis, C William; Sheehan, John K; Boucher, Richard C; Kesimer, Mehmet

    2014-07-01

    The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer-dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease.

  6. Mucinous carcinoma of breast with psammomatous calcification: report of a rare case with extensive axillary metastases.

    PubMed

    Bahadur, Shalini; Pujani, Mukta; Jetley, Sujata; Raina, Prabhat Kumar

    2014-01-01

    Pure mucinous carcinoma of the breast accounts for about 2% of all breast carcinomas and is associated with a favourable prognosis due to its lower nuclear grade and infrequent axillary or hematogenous metastases. Micropapillary variant of mucinous carcinoma breast has recently received attention as a unique form of invasive carcinoma of the breast exhibiting dual differentiation towards mucinous as well as micropapillary. The characteristic features for labeling a tumor as mucinous micropapillary carcinoma are micropapillary pattern, nuclear pleomorphism, hobnail cells and psammoma bodies in addition to the predominant mucinous component. Micropapillary mucinous carcinoma (MUMPC) when compared to pure mucinous carcinoma tends to have a higher nuclear grade, axillary lymph node metastases, lymphovascular invasion and overexpression of Her 2, p53 and Ki-67, thereby displaying an aggressive clinical behaviour. We present a rare case of micropapillary mucinous carcinoma to highlight the fact that this being a unique and rare variant of mucinous carcinoma should be recognized and reported as a separate category by the pathologists owing to its aggressive clinical behaviour and its influence on the nature of therapy.

  7. Expression of androgen, estrogen and progesterone receptors in mucinous carcinoma of the breast.

    PubMed

    Cho, Li-Chen; Hsu, Yung-Hsiang

    2008-05-01

    Hormone receptors play important roles in breast cancer. We investigated the expression of hormone receptors in breast cancer to evaluate the importance of hormone receptors in the clinicopathology of breast cancer. Androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PR) expression characteristics were evaluated using immunohistochemistry stain, comparing patient age, tumor size and axillary lymph node status for 23 pure mucinous and 105 non-mucinous infiltrating ductal carcinomas in the human female breast. Mucinous carcinoma with axillary lymph node metastasis occurred less frequently than non-mucinous carcinoma (11.8% vs. 55.2%; p = 0.01). Compared with the non-mucinous type, mucinous carcinoma specimens showed less AR expression (21.7% vs. 51.4%; p = 0.01) but more ER expression (78.3% vs. 52.4%; p = 0.02). In addition, AR expression was also associated with ER and/or PR coexpression (37/74, 50%) in infiltrating ductal carcinoma. But only three of 20 (15%) mucinous carcinoma specimens with AR expression had associated ER and/or PR coexpression. Our findings revealed that mucinous carcinoma samples from the breast show distinct clinicopathologic and hormone receptor expression features compared to non-mucinous carcinoma.

  8. Cysteamine and prostaglandin F2 beta stimulate rat gastric mucin release

    SciTech Connect

    Lamont, J.T.; Ventola, A.S.; Maull, E.A.; Szabo, S.

    1983-02-01

    Gastric mucin glycoproteins form an adherent gel over the surface epithelium that is thought to protect the stomach against chemical and physical damage. The purpose of this study was to measure the release of mucin glycoproteins from rat stomach after treatment with cysteamine and prostaglandin F2 beta, two structurally unrelated drugs that have been shown to protect the stomach against the noxious effects of alcohol and other damaging agents. Gastric mucin was separated into soluble (washout) and insoluble (adherent) phases before colorimetric quantitation of total mucin, protein-bound hexose, and sialic acid. Cysteamine produced a dose-dependent increase in release of soluble and gel mucin. Prostaglandin F2 beta caused a dose-dependent release of hexose-containing mucin but had no effect on sialic acid-containing glycoproteins. Sepharose 4B chromatography of both the soluble and adherent mucus revealed that greater than 90% was a high molecular weight glycoprotein fraction. N-Ethylmaleimide, a known inhibitor of cytoprotection by cysteamine, had no effect on mucin secretion. Similarly, indomethacin inhibited mucin secretion by cysteamine but did not significantly influence cytoprotection. Thus the secretion of mucin by cytoprotective agents is unlikely by itself to explain the ability of the stomach to resist chemical or physical damage.

  9. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  10. High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-10-18

    Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma

  11. Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis: cross-sectional imaging evaluation.

    PubMed

    Lee, Nam Kyung; Kim, Suk; Kim, Hyun Sung; Jeon, Tae Yong; Kim, Gwang Ha; Kim, Dong Uk; Park, Do Youn; Kim, Tae Un; Kang, Dae Hwan

    2011-11-21

    Various mucin-producing neoplasms originate in different abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appearance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also generally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Imaging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to water on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appropriate treatment.

  12. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine.

    PubMed

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L

    2015-10-20

    Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin.

  13. PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature.

    PubMed

    Ates Ozdemir, D; Usubutun, A

    2016-07-01

    Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.

  14. Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores

    PubMed Central

    Doyle, Sean P.; Nguyen, Kristine; Ribeiro, Carla M. P.; Vasquez, Paula A.; Forest, M. Gregory; Lethem, Michael I.; Dickey, Burton F.; Davis, C. William

    2015-01-01

    Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5–2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin

  15. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine

    PubMed Central

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L.

    2015-01-01

    Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin. PMID:26436698

  16. Pathologic classification of adenocarcinoma of lung.

    PubMed

    Van Schil, Paul E; Sihoe, Alan D L; Travis, William D

    2013-10-01

    Recently, the 1999/2004 World Health Organization (WHO) classification of adenocarcinoma became less useful from a clinical standpoint as most adenocarcinomas belonged to the mixed subtype and the term bronchioloalveolar carcinoma (BAC) gave rise to much confusion among clinicians. For these reasons a new adenocarcinoma classification was introduced in 2011 by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This represents an international, multidisciplinary effort joining pathologists, molecular biologists, pulmonary physicians, thoracic oncologists, radiologists, and thoracic surgeons. Currently, a distinction is made between pre-invasive lesions, minimally invasive and invasive lesions. The confusing term BAC is not used anymore and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Several aspects of this classification are discussed with main emphasis on its correlation with imaging techniques and its impact on diagnosis, treatment and prognosis. On chest computed tomography (CT) a distinction is made between solid and subsolid nodules, the latter comprising ground glass opacities (GGO), and partly solid lesions. Several studies incorporating CT and positron emission tomographic (PET) data show a good imaging-pathologic correlation. With the implementation of screening programs early lung cancer has become a hotly debated topic and sublobar resection is currently reconsidered for early lesions without lymph node involvement. This new classification will also have an impact on the TNM classification. Thoracic surgeons will continue to play a major role in the application, evaluation and further refinement of this new adenocarcinoma classification.

  17. Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.

    PubMed

    Lacroix-Triki, Magali; Suarez, Paula H; MacKay, Alan; Lambros, Maryou B; Natrajan, Rachael; Savage, Kay; Geyer, Felipe C; Weigelt, Britta; Ashworth, Alan; Reis-Filho, Jorge S

    2010-11-01

    Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the

  18. Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides.

    PubMed

    Kreda, Silvia M; Seminario-Vidal, Lucia; van Heusden, Catharina A; O'Neal, Wanda; Jones, Lisa; Boucher, Richard C; Lazarowski, Eduardo R

    2010-06-15

    Purinergic regulation of airway innate defence activities is in part achieved by the release of nucleotides from epithelial cells. However, the mechanisms of airway epithelial nucleotide release are poorly understood. We have previously demonstrated that ATP is released from ionomycin-stimulated airway epithelial goblet cells coordinately with mucin exocytosis, suggesting that ATP is released as a co-cargo molecule from mucin-containing granules. We now demonstrate that protease-activated-receptor (PAR) agonists also stimulate the simultaneous release of mucins and ATP from airway epithelial cells. PAR-mediated mucin and ATP release were dependent on intracellular Ca(2+) and actin cytoskeleton reorganization since BAPTA AM, cytochalasin D, and inhibitors of Rho and myosin light chain kinases blocked both responses. To test the hypothesis that ATP is co-released with mucin from mucin granules, we measured the nucleotide composition of isolated mucin granules purified based on their MUC5AC and VAMP-8 content by density gradients. Mucin granules contained ATP, but the levels of ADP and AMP within granules exceeded by nearly 10-fold that of ATP. Consistent with this finding, apical secretions from PAR-stimulated cells contained relatively high levels of ADP/AMP, which could not be accounted for solely based on ATP release and hydrolysis. Thus, mucin granules contribute to ATP release and also are a source of extracellular ADP and AMP. Direct release of ADP/AMP from mucin granules is likely to provide a major source of airway surface adenosine to signal in a paracrine faction ciliated cell A(2b) receptors to activate ion/water secretion and appropriately hydrate goblet cell-released mucins.

  19. Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides

    PubMed Central

    Kreda, Silvia M; Seminario-Vidal, Lucia; van Heusden, Catharina A; O’Neal, Wanda; Jones, Lisa; Boucher, Richard C; Lazarowski, Eduardo R

    2010-01-01

    Purinergic regulation of airway innate defence activities is in part achieved by the release of nucleotides from epithelial cells. However, the mechanisms of airway epithelial nucleotide release are poorly understood. We have previously demonstrated that ATP is released from ionomycin-stimulated airway epithelial goblet cells coordinately with mucin exocytosis, suggesting that ATP is released as a co-cargo molecule from mucin-containing granules. We now demonstrate that protease-activated-receptor (PAR) agonists also stimulate the simultaneous release of mucins and ATP from airway epithelial cells. PAR-mediated mucin and ATP release were dependent on intracellular Ca2+ and actin cytoskeleton reorganization since BAPTA AM, cytochalasin D, and inhibitors of Rho and myosin light chain kinases blocked both responses. To test the hypothesis that ATP is co-released with mucin from mucin granules, we measured the nucleotide composition of isolated mucin granules purified based on their MUC5AC and VAMP-8 content by density gradients. Mucin granules contained ATP, but the levels of ADP and AMP within granules exceeded by nearly 10-fold that of ATP. Consistent with this finding, apical secretions from PAR-stimulated cells contained relatively high levels of ADP/AMP, which could not be accounted for solely based on ATP release and hydrolysis. Thus, mucin granules contribute to ATP release and also are a source of extracellular ADP and AMP. Direct release of ADP/AMP from mucin granules is likely to provide a major source of airway surface adenosine to signal in a paracrine faction ciliated cell A2b receptors to activate ion/water secretion and appropriately hydrate goblet cell-released mucins. PMID:20421285

  20. Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis.

    PubMed

    Parvanescu, Alina; Cros, Jérôme; Ronot, Maxime; Hentic, Olivia; Grybek, Virginie; Couvelard, Anne; Levy, Philippe; Chanson, Philippe; Ruszniewski, Philippe; Sauvanet, Alain; Gaujoux, Sebastien

    2014-08-01

    GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.

  1. Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

    PubMed

    Matsuzaka, Suguru; Karasaki, Hidenori; Ono, Yusuke; Ogata, Munehiko; Oikawa, Kensuke; Tamakawa, Susumu; Chiba, Shin-Ichi; Muraki, Miho; Yokochi, Tomoki; Funakoshi, Hiroshi; Kono, Toru; Nagashima, Kazuo; Mizukami, Yusuke

    2016-07-01

    Adenosquamous carcinoma (ASC) is an uncommon variant of pancreatic neoplasm. We sought to trace the mode of tumor progression using specimens of ASC associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. A resected specimen of the primary pancreatic ASC, developed in a 72-year-old man, was subjected to mutation profiling using amplicon-targeted sequencing and digital polymerase chain reaction. DNA was isolated from each histological compartment including noninvasive IPMN, squamous cell carcinoma (SCC), and adenocarcinoma (AC). Histologically, an IPMN with a large mural nodule was identified. The invasive tumor predominantly consisted of SCC, and a smaller AC was found around the lesion. Squamous metaplasias were sporadically distributed within benign IPMNs. Mutation alleles KRAS and GNAS were identified in all specimens of IPMN including the areas of squamous metaplasia. In addition, these mutations were found in SCC and AC. Clear transition from flat/low-papillary IPMN to SCC indicated a potent invasion front, and the SCC compartment was genetically unique, because the area has a higher frequency of mutation KRAS. The invasive tumors with distinct histological appearances shared the form of noninvasive IPMN as a common precursor, rather than de novo cancer, suggesting the significance of a genetic profiling scheme of tumors associated with IPMN.

  2. K-Ras and cyclooxygenase-2 coactivation augments intraductal papillary mucinous neoplasm and Notch1 mimicking human pancreas lesions

    PubMed Central

    Chiblak, Sara; Steinbauer, Brigitte; Pohl-Arnold, Andrea; Kucher, Dagmar; Abdollahi, Amir; Schwager, Christian; Höft, Birgit; Esposito, Irene; Müller-Decker, Karin

    2016-01-01

    Mutational activation of K-Ras is an initiating event of pancreatic ductal adenocarcinomas (PDAC) that may develop either from pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasms (IPMN). Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is causally related to pancreatic carcinogenesis. Here, we deciphered the impact of COX-2, a key modulator of inflammation, in concert with active mutant K-RasG12D on tumor burden and gene expression signature using compound mutant mouse lines. Concomitant activation of COX-2 and K-RasG12D accelerated the progression of pancreatic intraepithelial lesions predominantly with a cystic papillary phenotype resembling human IPMN. Transcriptomes derived from laser capture microdissected preneoplastic lesions of single and compound mutants revealed a signature that was significantly enriched in Notch1 signaling components. In vitro, Notch1 signaling was COX-2-dependent. In line with these findings, human IPMN stratified into intestinal, gastric and pancreatobillary types displayed Notch1 immunosignals with high prevalence, especially in the gastric lesions. In conclusion, a yet unknown link between activated Ras, protumorigenic COX-2 and Notch1 in IPMN onset was unraveled. PMID:27381829

  3. Giant congenital melanocytic nevus*

    PubMed Central

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion. PMID:24474093

  4. Giant congenital melanocytic nevus.

    PubMed

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.

  5. Mixed Mucinous and Infiltrating Carcinoma Occurring in Male Breast- Study of Clinico-Pathological Features: A Rare Case Report.

    PubMed

    Gupta, Kavita; Sharma, Swati; Kudva, Ranjini; Kumar, Sandeep

    2015-06-01

    Mucinous carcinoma is a less common histologic variant of breast cancer. Cases of mucinous carcinomas in male breast are extremely rare. Here, we describe a case of mixed mucinous carcinoma i.e. mucinous carcinoma with infiltrating ductal carcinoma component and showing apocrine differentiation in a 73-year-old man. This uncommon tumour entity has dismal prognosis and treatment depends largely on the tumour type, size, lymph node involvement and hormonal status.

  6. Mucin aggregation from a rod-like meso-scale model

    NASA Astrophysics Data System (ADS)

    Moreno, Nicolas; Perilla, Jairo E.; Colina, Coray M.; Lísal, Martin

    2015-05-01

    Dissipative particle dynamics, a meso-scale particle-based model, was used to study the aggregation of mucins in aqueous solutions. Concentration, strength of the mucin-water interactions, as well as the effects of size, shape, and composition of the model molecules were studied. Model proteins were represented as rod-like objects formed by coarse-grained beads. In the first model, only one type of beads formed the mucin. It was found that all the surfaces were available to form aggregates and the conformation of the aggregates was a function of the strength of the mucin-water interaction. With this model, the number of aggregates was unaffected by the initial position of the mucins in the simulation box, except for the lowest mucin concentration. In a more refined mucin model, two kinds of beads were used in the molecule in order to represent the existence of cysteine-like terminal groups in the actual molecule. With this new scheme, aggregation took place by the interaction of the terminal groups between model molecules. The kinetic analysis of the evolution of the number of aggregates with time was also studied for both mucin models.

  7. Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide: effect of sulglycotide.

    PubMed

    Piotrowski, J; Majka, J; Murty, V L; Czajkowski, A; Slomiany, A; Slomiany, B L

    1994-09-01

    1. A receptor for mucin was isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin. 2. The receptor protein displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surfaces. The optimum for mucin binding occurred at 60-100 micrograms/ml, while the values for the receptor were 2.0-3.1 micrograms/ml. 3. The mucin binding to the receptor was susceptible to Helicobacter pylori lipopolysaccharide which caused maximum inhibition of 91% at 30 mu/ml. This inhibitory effect of the lipopolysaccharide was abolished by a gastroprotective agent, sulglycotide. 4. The effect of sulglycotide was dose dependent and at 50 micrograms/ml produced a 94% restoration in receptor-mucin binding. Furthermore, sulglycotide was also capable of enhancing (97%) the mucin binding to its receptor in the absence of the lipopolysaccharide. 5. The results demonstrate that H. pylori through its lipopolysaccharide interferes in the interaction of mucin with gastric epithelial surfaces and that a gastroprotective agent, sulglycotide, counteracts this effect, and hence is capable of preventing the loss of mucin coat continuity occurring with H. pylori infection.

  8. Effect of reserpine on the histochemical and biochemical properties of rat intestinal mucin

    SciTech Connect

    Forstner, J.; Roomi, N.; Khorasani, R.; Kuhns, W.; Forstner, G. )

    1991-04-01

    Biochemical and histochemical parameters of intestinal mucins were examined in control and reserpine-treated rats. An assay for intestinal mucin sulfotransferase was developed and the activity shown to increase 3.4 times over control levels in rats given intraperitonal reserpine (0.5 mg/kg body wt) daily for 7 days. Histochemical staining of intestinal sections revealed an increase in sulfomucins in goblet cells of reserpine-treated rats. The effects were prominent as early as 1 day following injection, particularly in the distal third of the small intestine, and during the next 6 days these changes spread progressively to the middle and proximal thirds. After 3 days of treatment mucins were purified from each intestinal segment and compared to control mucins with respect to composition and (35S)NaSO{sub 4} incorporation. Although individual amino acid and carbohydrate molar ratios were unchanged, the total carbohydrate and sulfate content of mucins in treated animals was elevated (two to three times above control) in the middle and distal thirds of the intestine. In vivo ({sup 35}S)SO{sub 4} incorporation into these mucins was also proportionaltely elevated, and was targetted to O-linked oligosaccharide side chains. These findings are consistent with an action of reserpine causing an increased production of mucin which is enriched in glycoprotein components bearing sulfated oligosaccharide chains. The relevance of these findings to the production of hypersulfated and hyperglycosylated mucins in cystic fibrosis is discussed.

  9. Cytomorphologic features of advanced lung adenocarcinomas tested for EGFR and KRAS mutations: a retrospective review of 50 cases.

    PubMed

    Marotti, Jonathan D; Schwab, Mary C; McNulty, Nancy J; Rigas, James R; DeLong, Peter A; Memoli, Vincent A; Tsongalis, Gregory J; Padmanabhan, Vijayalakshmi

    2013-01-01

    Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI), mucin, necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation. DNA was extracted from a paraffin-embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real-time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in codon 12 and one mutation in codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on paraffin block (P = 0.039) correlated with the presence of EGFR mutations. The presence of necrosis (P = 0.030), squamoid features (P = 0.048), and poorly differentiated tumors (P = 0.025) were more likely to be identified in the KRAS positive group.

  10. Mucins and Their Sugars. Critical Mediators of Hyperreactivity and Inflammation

    PubMed Central

    Raclawska, Dorota S.; Ttofali, Fani; Fletcher, Ashley A.; Harper, Daniel N.; Bochner, Bruce S.; Janssen, William J.

    2016-01-01

    Excessive mucus causes severe airflow obstruction in fatal asthma. It is also present in mild to moderate disease, but is poorly understood and treated. Mucus overproduction is associated with dysregulated expression of the mucins MUC5AC and MUC5B. Whereas increased MUC5AC is a consistent finding, MUC5B varies—remaining stably produced in some patients but strongly repressed in others (>90%). Patients with lower MUC5B display worsened asthma phenotypes including airway hyperreactivity (AHR) to methacholine (MCh) and eosinophilic inflammation. To better understand the roles of mucins in asthma, we generated Muc5ac and Muc5b knockout (−/−) mice. AHR to MCh was abolished in antigen-challenged Muc5ac−/− mice, due to prevention of heterogeneous mucous plugging that occurred in allergic wild-type mice during MCh-induced bronchoconstriction. Thus, in addition to the established role of smooth muscle–mediated airway narrowing, Muc5ac is an essential noncontractile AHR component. We also found that, unlike Muc5ac−/− mice, Muc5b-deficient mice were not protected from asthma phenotypes. Furthermore, whereas inflammation was unaffected by Muc5ac deficiency, it was exaggerated in the absence of Muc5b. On the basis of these differential effects, we are now determining how asthma phenotypes are regulated by mucin isoform specificity. Glycosylation is dramatically different: Muc5ac is heavily fucosylated whereas Muc5b is mainly sialylated. Fucosylation increases mucus viscoelasticity, and FUT2, the enzyme that catalyzes mucin α1,2-fucosylation, is associated with severe asthma exacerbation risk. Sialylation is required for binding to siglec (sialic acid–binding immunoglobulin-like lectin) receptors on leukocytes. Eosinophils express Siglec-F (mouse) or Siglec-8 (human). Engagement by sialoside ligands induces eosinophil apoptosis, and Muc5b via sialylated termini that require the α2,3-sialyltransferase ST3Gal3 for synthesis binds Siglec-F and induces apoptosis

  11. Mucinous subtype of invasive ductal carcinoma arising within a fibroadenoma.

    PubMed

    Monsefi, Nahid; Nikpour, Hossein; Safavi, Moienadin; Lashkarizadeh, Mohammad Reza; Dabiri, Shahriar

    2013-06-01

    Fibroadenoma is a common benign tumor observed during the second and third decades of life. Malignancy transformation in the epithelial component of a fibroadenoma is rare and can occur 20 years after its diagnosis. Mammographic findings in this phenomenon include indistinct margins and microcalcifications. Here we present a 58-year-old woman with a mobile, lateral upper quadrant mass that was rather firm when palpated. The mammography showed a lobulated mass without calcification suggestive of a benign process, most probably fibroadenoma. However the excisional biopsy contained both an intracanalicular fibroadenoma and invasive ductal carcinoma with mucinous components.

  12. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

    PubMed Central

    2012-01-01

    Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found

  13. Mucin can enhance growth, biofilm formation, and survival of Streptococcus mutans.

    PubMed

    Mothey, Deepa; Buttaro, Bettina A; Piggot, Patrick J

    2014-01-01

    Streptococcus mutans is a member of the dental plaque and is the primary causative agent of dental caries. It can survive extended periods of starvation, which may occur in different niches within the oral cavity. We have found that mucin compensated for the absence of amino acids to promote exponential growth and biofilm formation of S. mutans in minimal medium supplemented with glucose and sucrose, respectively. Mucin extended survival in conditions where there was no net growth provided the operon encoding the pyruvate dehydrogenase complex was intact. Mucin extended survival in conditions of amino acid sufficiency provided the tagatose pathway for galactose utilization was intact, suggesting that S. mutans can scavenge sufficient galactose from mucin to enhance survival, although not to serve as a primary carbon and energy source. The results suggest that mucin has a metabolic role in promoting survival of S. mutans.

  14. Repression of flagella motility in enterohemorrhagic Escherichia coli O157:H7 by mucin components.

    PubMed

    Kim, Jong Chul; Yoon, Jang W; Kim, Cheorl-Ho; Park, Mi-Sun; Cho, Seung-Hak

    2012-07-13

    Whole genome-scale transcriptome analysis of enterohemorrhagic Escherichia coli (EHEC) O157:H7 EDL933 was performed to investigate the influence of mucin components on the EHEC gene expression. Here we report that the 732 candidate genes were differentially expressed by the presence of 0.5% porcine stomach mucin, including the 8 flagella-related genes. Quantitative real-time PCR analyses revealed that the transcription expression of the flg genes (encoding the structural components for flagella basal body) was down-regulated by the mucin components. Indeed, bacterial swarming motility was drastically reduced when grown on 0.3% trypton agar plates containing the mucin. These results imply that gastrointestinal (GI) mucin is a possible environmental signal which negatively regulates the flagellation of EHEC O157:H7 in the GI tract.

  15. Residual mucin and response after neoadjuvant chemotherapy (NAC) in breast cancer.

    PubMed

    Jove, Maria; Verghese, Eldo; Sharma, Nisha; Lane, Sally

    2016-05-06

    Neoadjuvant chemotherapy (NAC) is the standard of care for patients with breast cancer with inoperable disease or smaller tumours who might benefit from a conservative surgery after downstaging of their disease. Nevertheless, evidence shows that preoperative and postoperative chemotherapy are equivalent in terms of long-term survival. Response and histological changes after NAC have been widely studied in invasive ductal carcinoma not otherwise specified, but there is a paucity of characterisation of patterns of response to chemotherapy in less frequent histological types. We report extensive residual mucin deposits after chemotherapy in a woman with locally advanced breast cancer and a prominent mucinous component at diagnosis. Interestingly, residual mucin was co-located with the initial tumour, in the breast as well as in the axillary lymph nodes. The distribution of mucin may be a valuable marker of the extent of mucinous carcinomas prior to NAC.

  16. An Innocent Giant

    PubMed Central

    Solanki, Lakhan Singh; Dhingra, Mandeep; Raghubanshi, Gunjan; Thami, Gurvinder Pal

    2014-01-01

    A cutaneous horn (cornu cutaneum) is a protrusion from the skin composed of a cornified material. It may be associated with a benign, premalignant, or malignant lesion at the base, masking numerous dermatoses. In a 24-year-old female, a giant cutaneous horn arising from a seborrheic keratosis located on the leg is presented. This case has been reported to emphasize that a giant cutaneous horn may also occur in young patients, even in photoprotected areas, and are not always associated with malignancy. PMID:25484426

  17. Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

    SciTech Connect

    Oberholzer, Katja; Menig, Matthias; Kreft, Andreas; Schneider, Astrid; Junginger, Theodor; Heintz, Achim; Kreitner, Karl-Friedrich; Hoetker, Andreas M.; Hansen, Torsten; Dueber, Christoph; Schmidberger, Heinz

    2012-02-01

    Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

  18. Regulation of mucous differentiation and mucin gene expression in the tracheobronchial epithelium.

    PubMed

    Gray, T; Koo, J S; Nettesheim, P

    2001-03-07

    The goal of our studies is to elucidate mechanisms that control and modulate mucous differentiation and mucin gene expression in the conducting airways. We used cultures of normal human tracheobronchial epithelial (NHTBE) cells that were shown to secrete two major airway mucins, namely MUC5AC and MUC5B as well as several other secretory products. Mucous differentiation and expression of MUC2, MUC5AC, MUC5B and MUC7, but not MUCi, MUC4, and MUC8 mucin genes, were shown to be retinoic acid- (RA) or retinol-dependent. We found that RA control of mucin genes was mediated by the retinoid acid receptors RAR alpha and, to a lesser extent, by RAR gamma. Our studies also showed that other important bioregulators such as thyroid hormone (T3) and epidermal growth factor (EGF) modulate basal expression of mucin genes, interacting with RA in a concentration-dependent manner. T3, which binds to thyroid receptors (TRs) belonging to the same superfamily of steroid hormone nuclear receptors as the RARs, inhibits mucin gene expression, particularly MUC5AC. One possible mechanism of this T3 effect is downregulation of RAR proteins, which are critical for mucin gene expression. However, we also found that T3 inhibits MUC5AC transcription.EGF, which had previously been shown to stimulate mucin expression and mucin secretion in cultured rat tracheal epithelial (RTE) cells, inhibited mucin secretion in human bronchial epithelial cell cultures. This effect was EGF concentration- and time-dependent and was progressively abolished by increasing the RA concentration. Subsequent studies suggested that the inhibitory effects of high concentrations of EGF may result from selective reduction of MUC5AC expression. These studies thus point to potentially important species differences in the mechanisms regulating mucous production, and they also confirm previous findings indicating differential regulation of MUC5AC and MUC5B gene expression.

  19. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    SciTech Connect

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho . E-mail: keesh@korea.ac.kr

    2005-08-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear {beta}-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear {beta}-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3{beta} activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death.

  20. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  1. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  2. Small angle neutron scattering (SANS) study of gastric mucin solutions

    NASA Astrophysics Data System (ADS)

    Hong, Z.; Bansil, R.; Waigh, T.; Turner, B.; Bhaskar, K. R.; Afdhal, N.; Lal, J.

    2002-03-01

    We report the first results from a SANS study of purified porcine gastric mucin solutions in D2O. The ability of this glycoprotein to protect the stomach epithelium from acid damage, may be due to a pH dependent conformational transition which leads to gelation at low pH Cao et. al. (Biophysical. J. 76, 1250, 1999). SANS measurements were made over the concentration range of 1 -15 mg/ml at pH 7, 4 and 2. The data indicate that at pH 7 the excluded volume exponent is 1.7, characteristic of swollen chains whereas at pH 2 this exponent increases to 2, indicating theta or poor solvent conditions, consistent with the hydrophobic interactions increasing at lower pH. From a Guinier analysis of the 1mg/ml data at low q's (0.003- 0.007 Å-1) we estimate the cross section radius of the effective cylinder to be 23nm and its length as 96nm in an unbuffered sample, i.e. close to pH 7. In the intermediate q-range (0.01 -0.1Å-1) at pH 7 a fit to the Debye chain gives radius of gyration Rg of 16nm. Mucin is best modelled as an elongated micelle with a cylindrical or worm-like chain to represent the protein core and the sugar chains forming the corona. Results of such calculations will be presented.

  3. Hepatocellular carcinoma with characteristic mucin production: a case report

    PubMed Central

    Lee, Kyung Hwa; Kim, Young Bog; Cho, Sung Bum; Lee, Min Cheol; Park, Chang Soo

    2009-01-01

    We present a unique case of hepatocellular carcinoma with mucin-producing gland formation. A 53-year-old man with hepatitis B infection presented with weight loss for the past month. Computed tomography demonstrated a 10 × 9.8 cm mass in the right hepatic lobe accompanied by cirrhotic changes in the hepatic parenchyma. Right hepatectomy was performed, and the tumor cut surface showed a poorly-circumscribed, white to pink tumor with numerous nodules and extensive necrosis. Microscopically, the tumor was composed of thick trabeculae and large, irregularly-shaped islands, both of which were filled with pleomorphic eosinophilic hepatoid cells or gland-forming columnar cells with mucin production. Those cells were immunoreactive for cytokeratin 19 in both the trabeculae and the glands. In some tumor cells, limited immunoreactivity for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen was noted. The cells forming thick trabeculae were focally positive for hepatocyte paraffin 1 and alpha-fetoprotein. We suggest that this tumor shows bidirectional differentiation into hepatocytes and cholangiocytes, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells which can imply divergent differentiation. PMID:19918544

  4. Viscoelastic Properties and Dynamics of Porcine Gastric Mucin

    SciTech Connect

    Celli,J.; Gregor, B.; Turner, B.; Afdhal, N.; Bansil, R.; Erramilli, S.

    2005-01-01

    Gastric mucin is a glycoprotein known to undergo a pH-dependent sol-gel transition that is crucial to the protective function of the gastric mucus layer in mammalian stomachs. We present microscope-based dynamic light scattering data on porcine gastric mucin at pH 6 (solution) and pH 2 (gel) with and without the presence of tracer particles. The data provide a measurement of the microscale viscosity and the shear elastic modulus as well as an estimate of the mesh size of the gel formed at pH 2. We observe that the microscale viscosity in the gel is about 100-fold lower than its macroscopic viscosity, suggesting that large pores open up in the gel reducing frictional effects. The data presented here help to characterize physiologically relevant viscoelastic properties of an important biological macromolecule and may also serve to shed light on diffusive motion of small particles in the complex heterogeneous environment of a polymer gel network.

  5. Middle ear adenoma. A tumor displaying mucinous and neuroendocrine differentiation.

    PubMed

    Wassef, M; Kanavaros, P; Polivka, M; Nemeth, J; Monteil, J P; Frachet, B; Tran Ba Huy, P

    1989-10-01

    Middle ear adenoma (MEA) is a distinctive, rare entity that appears to be derived from the lining epithelium of the middle ear mucosa. We report four cases of MEA displaying the typical histologic growth pattern. Two distinct tumor cell immunophenotypes were identified in all cases; the first type exhibited positivity with anti-epithelial membrane antigen and anti-keratin antibodies, and the second type showed immunoreactivity with anti-keratin, anti-vimentin, and anti-neuron-specific enolase antibodies. Ultrastructural studies revealed bidirectional mucinous and neuroendocrine differentiation, demonstrated by the presence of two distinct cell types containing apically located mucous granules and basally concentrated neuroendocrine granules, respectively. The presence of neuroendocrine differentiation was supported by the immunohistochemical detection of vasoactive intestinal polypeptide in the tumor cells in one case and neuron-specific enolase in three cases. These findings suggest that the potential for mixed mucinous/neuroendocrine differentiation described in other endodermally derived tumors also exists in middle ear mucosa. We also believe that the rare lesions diagnosed as primary carcinoid tumors of the middle ear might in fact be MEA with predominant or only neuroendocrine differentiation. The clinical course of our four cases and our review of the pertinent literature confirm the benign nature of MEA and indicate that these tumors should be treated by complete local excision without additional therapy.

  6. Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

    PubMed Central

    Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo

    2014-01-01

    Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management. PMID:25110429

  7. Giant scrotal elephantiasis.

    PubMed

    Kuepper, Daniel

    2005-02-01

    How much can a man carry? Penoscrotal elephantiasis is a debilitating syndrome. This is a case report of a patient with giant genital elephantiasis secondary to long-standing lymphogranuloma venereum infection in Ethiopia. Complete surgical resection of the pathologic tissue and penile reconstruction was undertaken with good cosmetic and functional results.

  8. Electroluminescence of Giant Stretchability.

    PubMed

    Yang, Can Hui; Chen, Baohong; Zhou, Jinxiong; Chen, Yong Mei; Suo, Zhigang

    2016-06-01

    A new type of electroluminescent device achieves giant stretchability by integrating electronic and ionic components. The device uses phosphor powders as electroluminescent materials, and hydrogels as stretchable and transparent ionic conductors. Subject to cyclic voltage, the phosphor powders luminesce, but the ionic conductors do not electrolyze. The device produces constant luminance when stretched up to an area strain of 1500%.

  9. Identification of the mucin-binding adhesin of Pseudomonas cepacia isolated from patients with cystic fibrosis.

    PubMed Central

    Sajjan, S U; Forstner, J F

    1992-01-01

    In previous experiments, we have shown that isolates of Pseudomonas cepacia from sputa of patients with cystic fibrosis (CF), particularly those with severe lung infection, exhibited specific binding to purified respiratory or intestinal mucins (U. Sajjan, M. Corey, M. Karmali, and J. Forstner, J. Clin. Invest. 89:648-656, 1992). The present report describes the identification of the adhesin as a protein located on fimbriae of mucin-binding P. cepacia. From a total of 53 isolates available (from 22 patients with CF), we used three mucin-binding and three non-mucin-binding isolates for our experiments. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude P. cepacia homogenates was performed, the separated proteins were blotted onto nitrocellulose and overlaid with purified mucin, and mucin-binding components were detected with an antimucin antibody and then a second-antibody-alkaline phosphatase conjugate system. Only mucin-binding isolates exhibited a positively stained band at an Mr of 22,000. The 22-kDa protein was purified, and a polyclonal antibody specific for it was developed in rabbits. By electron microscopy and immunogold labelling, both the antibody and mucin (separately) were localized to pili present over the entire surface of the bacterial cells. Non-mucin-binding isolates did not have (or had very few) pili and did not stain with either mucin or the antibody to the 22-kDa protein. The purified 22-kDa protein and its antibody were each able to inhibit piliated P. cepacia binding to mucin. The amino acid composition of the 22-kDa protein was dissimilar to those of the major pilin proteins of Escherichia coli (type 1 pilus) and P. aeruginosa (PAK and PAO1 strains). Both the pili of P. aeruginosa PAK and PAO1 and antibodies to these pili failed to inhibit P. cepacia binding to mucin. Thus, P. cepacia adhesion to mucin is mediated by a pilin-associated 22-kDa protein which differs from epithelial-cell-binding pilin proteins of P. aeruginosa

  10. Adenocarcinoma of Meckel's cave: case report.

    PubMed

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L

    1995-12-01

    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  11. Natural history of intraductal papillary mucinous neoplasms (IPMN): current evidence and implications for management.

    PubMed

    Bassi, Claudio; Sarr, Michael G; Lillemoe, Keith D; Reber, Howard A

    2008-04-01

    Intraductal papillary mucinous neoplasms (IPMNs) show varying degrees of dysplasia throughout the neoplasm that can range from adenoma to invasive carcinoma, with dysplastic changes of borderline neoplasms and carcinoma in situ in between. An understanding of the natural history, and especially the required time to transform into either carcinoma in situ or an invasive adenocarcinoma, is critically important for management policy. This topic serves as the rationale for the present analysis. At the beginning of February 2007, using the key word "IPMN" in PubMed, we initially selected 119 publications using the principal criteria as defined by the WHO classification. We identified 20 appropriate original reports and one consensus paper. Neither randomized control trials (RCT) or systematic reviews of RCTs (level 1 evidence) nor cohort studies or reviews of cohort studies (level 2 evidence) have been published. Only one report fit the criteria for level 3 evidence (case control study). Nineteen papers satisfied criteria for level 4 (cases series) and two for level 5 (expert opinion publication). After additional review and analysis, we considered only six reports to be "cornerstone papers" of merit for the final review. Clues to the natural history of IPMNs can be gained by using several methods to examine the articles: (a) to verify different prognoses between main and side branch duct subtypes; (b) to compare the average age of patients with benign vs. malignant IPMNs; (c) to summarize the findings of nonoperative, observational studies based on follow up by clinical, biochemical, and imaging techniques without operative resection; (d) to determine the prognostic importance of the status of the resection margin; and (e) to follow patients clinically after surgical resection. Although important aspects of the natural history of IPMN are still unknown, the following conclusions can be drawn: (1) Branch-duct IPMNs are less aggressive than main-duct IPMNs. (2

  12. Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion

    PubMed Central

    Dawson, Paul A.; Lourie, Rohan; Hutson, Peter; Tong, Hui; Grencis, Richard K.

    2017-01-01

    Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by TH2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong TH2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection. PMID:28192541

  13. Candida albicans Shed Msb2 and Host Mucins Affect the Candidacidal Activity of Salivary Hst 5

    PubMed Central

    Puri, Sumant; Friedman, Justin; Saraswat, Darpan; Kumar, Rohitashw; Li, Rui; Ruszaj, Donna; Edgerton, Mira

    2015-01-01

    Salivary Histatin 5 (Hst 5) is an antimicrobial peptide that exhibits potent antifungal activity towards Candida albicans, the causative agent of oral candidiasis. However, it exhibits limited activity in vivo, largely due to inactivation by salivary components of both host and pathogen origin. Proteins secreted by C. albicans during infection such as secreted aspartyl proteases (Saps) and shed mucin Msb2 can reduce Hst 5 activity; and human salivary mucins, while suggested to protect Hst 5 from proteolytic degradation, can entrap peptides into mucin gels, thereby reducing bioavailability. We show here that Sap6 that is secreted during hyphal growth reduces Hst 5 activity, most likely a result of proteolytic degradation of Hst 5 since this effect is abrogated with heat inactivated Sap 6. We further show that just like C. albicans shedding Msb2, mammalian mucins, fetuin and porcine gut mucin (that is related to salivary mucins), also reduce Hst 5 activity. However, we identify mucin-like protein-induced changes in C. albicans cell morphology and aggregation patterns, suggesting that the effect of such proteins on Hst 5 cannot be interpreted independently of their effect on yeast cells. PMID:26529023

  14. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    PubMed

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2013-08-01

    Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.

  15. Analysis of mucin composition in gastric juices of chronic rheumatic patients with upper gastrointestinal damage.

    PubMed

    Ikezawa, Tomoaki; Ichikawa, Takafumi; Adachi, Ken; Sugano, Satoshi; Ojima, Tatsuya; Nakamura, Youko; Watanabe, Yukio; Ishihara, Kazuhiko

    2005-08-01

    Assessment of the mucin subclasses in the gastric juices of severe chronic rheumatoid arthritis (RA) patients was compared with non-RA cases which received the eradication treatment of Helicobacter pylori (H. pylori). Gastric juice samples were obtained from 8 RA patients (5 for H. pylori-negative and 3 for H. pylori-positive) and 5 control subjects in which we confirmed the successful eradication of H. pylori. The gastric luminal mucins were extracted and isolated by the ethanol precipitation method. These mucin solutions were digested with chymotrypsin, dialyzed, lyophilized, and redissolved. The obtained specimen was applied to an ion exchange column containing DEAE-Sepharose CL-6B and eluted with a discontinuous salt gradient in three salt steps. The gastric luminal mucins were divided into three fractions based on the distinctive sialic acid content. The proportion of acidic mucin rich in sialic acid from the gastric juice of RA patients without the H. pylori infection was significantly lower than those RA patients with H. pylori or the control subjects. A decrease in the acidic mucin content after eradication of H. pylori was commonly observed in all the control subjects. Our investigation raises the possibility that the gastric mucosae of RA patients have resistance against H. pylori infection. And the analysis of the composition in the gastric luminal mucin may be a very useful tool for the evaluation of gastric homeostasis in RA patients.

  16. The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome

    PubMed Central

    Ford, Amina A.; Wang, Tiffany; Li, Lily; Kesimer, Mehmet

    2016-01-01

    Summary Chronic lung diseases such as cystic fibrosis, chronic bronchitis and asthma, are characterized by hypersecretion and poor clearance of mucus, which are associated with poor prognosis and mortality. Little is known about the relationship between the biophysical properties of mucus and its molecular composition. The mucins MUC5B and MUC5AC are traditionally believed to generate the characteristic biophysical properties of airway mucus. However, the contribution of hundreds of globular proteins to the biophysical properties of mucus is not clear. Approximately one-third of the total mucus proteome comprises distinct, multi-protein complexes centered around airway mucins. These complexes constitute a discrete entity we call the “mucin interactome”. The data suggest that while the majority of these proteins interact with mucins via electrostatic and weak interactions, some interact through very strong hydrophobic and/or covalent interactions. Using reagents that interfere with protein-protein interactions, the complexes can be disassembled, and mucus rheology can be dramatically altered. Using MUC5B-glutathione S-transferase (GST) and MUC5B-galectin-3 as a representative of these interactions, we provide evidence that individual mucin protein interactions can alter the biophysical properties of mucus and modulate the biological function of the protein. We propose that the key mechano- and bio-active functions of mucus depend on the dynamic interactions between mucins and globular proteins. These observations challenge the paradigm that mucins are the only molecules that confer biophysical properties of mucus. These observations may ultimately lead to a greater understanding of the system and guide the development of strategies for more effective interventions using better therapeutic agents. PMID:27072609

  17. High risk of acute pancreatitis after endoscopic ultrasound-guided fine needle aspiration of side branch intraductal papillary mucinous neoplasms

    PubMed Central

    Siddiqui, Ali A.; Shahid, Haroon; Shah, Apeksha; Khurana, Tanvi; Huntington, William; Ghumman, Saad S.; Loren, David E.; Kowalski, Thomas E.; Laique, Sobia; Hayat, Umar; Eloubeidi, Mohamad A.

    2015-01-01

    Background and Objectives: Data on the risk of acute pancreatitis following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions are limited. The aim of our study was to evaluate the frequency of acute pancreatitis after EUS-FNA of pancreatic cysts and solid lesions, and determine whether there was a difference in pancreatitis risk in patients with side branch intraductal papillary mucinous neoplasms (SB-IPMN). Patients and Methods: A retrospective review of patients who underwent EUS-FNA of pancreatic cysts and solid lesions was performed. The primary outcome measure was development of acute pancreatitis after EUS-FNA. Factors associated with acute pancreatitis were examined by statistical analysis to determine independent predictors of acute pancreatitis. Statistical significance was determined at a P ≤ 0.05. Results: We identified 186 patients with pancreatic cystic lesions and 557 with solid lesions in which EUS-FNA was performed. The median size of the cysts was 19 mm (range: 10-66 mm). There were 37 IPMNs, 33 mucinous cystic neoplasms, 58 serous cysts and 46 pseudocysts and 12 solid-cystic ductal carcinomas. The majority of patients (75%) with solid lesions were diagnosed with adenocarcinoma. Patients with pancreatic cysts had a statistically greater frequency of developing pancreatitis after EUS-FNA when compared to those with solid lesions (2.6% vs. 0.36% respectively; P = 0.13). In patients with cysts, there were no statistically significant differences between the two groups (with and without pancreatitis) with regard to a cyst location, size of the cyst, and number of needle passes or trainee involvement. Patients with SB-IPMN had a statistically higher frequency of pancreatitis after EUS-FNA compared to those with other cyst types (8% vs. 1.3% respectively; odds ratio = 6.4, 95% confidence intervals = 1.0-40.3, P = 0.05). Discussion: Patients with SB-IPMN are at a higher risk of developing acute pancreatitis after

  18. Changes in Saliva Rheological Properties and Mucin Glycosylation in Dry Mouth.

    PubMed

    Chaudhury, N M A; Shirlaw, P; Pramanik, R; Carpenter, G H; Proctor, G B

    2015-12-01

    Saliva is vital for the maintenance of normal oral physiology and mucosal health. The loss of salivary function can have far-reaching consequences, as observed with dry mouth, which is associated with increased orodental disease, speech impairment, dysphagia, and a significant negative effect on quality of life. The timely diagnosis of oral dryness is vital for the management of orodental disease and any associated often-undiagnosed systemic disease (e.g., Sjögren syndrome). Our aim was to investigate differences in mucin glycoproteins and saliva rheological properties between sufferers and nonsufferers of dry mouth in order to understand the relationship between saliva composition, rheological properties, and dryness perception and provide additional potential diagnostic markers. All patients exhibited objective and subjective oral dryness, irrespective of etiology. Over half of the patients (n = 20, 58.8%) had a saliva secretion rate above the gland dysfunction cutoff of 0.1 mL/min. Mucin (MUC5B and MUC7) concentrations were generally similar or higher in patients. Despite the abundance of these moisture-retaining proteins, patients exhibited reduced mucosal hydration (wetness) and significantly lower saliva spinnbarkeit (stringiness), suggesting a loss of the lubricating and retention/adhesion properties of saliva, which, at least partially, are associated with mucin glycoproteins. Over 90% of patients with dry mouth (DMPs) consistently had unstimulated whole mouth saliva (UWMS) spinnbarkeit below the proposed normal cutoff (10 mm). Further analysis of mucins revealed the reduced glycosylation of mucins in DMPs compared to healthy controls. Our data indicate that UWMS mucin concentrations are not reduced in dry mouth but that the mucin structure (glycosylation) is altered. UWMS from DMPs had reduced spinnbarkeit, the assessment of which, in conjunction with sialometry, could improve sensitivity for the diagnosis of dry mouth. Additionally, it may be useful to

  19. Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

    PubMed Central

    Flynn, Jeffrey M.; Niccum, David; Dunitz, Jordan M.

    2016-01-01

    Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

  20. A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

    PubMed Central

    Sinha, Jessica; Cao, Zheng; Dai, Jianliang; Tang, Huiyuan; Partyka, Katie; Hostetter, Galen; Simeone, Diane M.; Feng, Ziding; Allen, Peter J.; Brand, Randall E.; Haab, Brian B.

    2016-01-01

    Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts. PMID:27992432

  1. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction.

    PubMed

    Schroeder, Bradley W; Verhaeghe, Catherine; Park, Sung-Woo; Nguyenvu, Louis T; Huang, Xiaozhu; Zhen, Guohua; Erle, David J

    2012-08-01

    Mucins are gel-forming proteins that are responsible for the characteristic viscoelastic properties of mucus. Mucin overproduction is a hallmark of asthma, but the cellular requirements for airway mucin production are poorly understood. The endoplasmic reticulum (ER) protein anterior gradient homolog 2 (AGR2) is required for production of the intestinal mucin MUC2, but its role in the production of the airway mucins MUC5AC and MUC5B is not established. Microarray data were analyzed to examine the relationship between AGR2 and MUC5AC expression in asthma. Immunofluorescence was used to localize AGR2 in airway cells. Coimmunoprecipitation was used to identify AGR2-immature MUC5AC complexes. Agr2(-/-) mice were used to determine the role of AGR2 in allergic airway disease. AGR2 localized to the ER of MUC5AC- and MUC5B-producing airway cells and formed a complex with immature MUC5AC. AGR2 expression increased together with MUC5AC expression in airway epithelium from "Th2-high" asthmatics. Allergen-challenged Agr2(-/-) mice had greater than 50% reductions in MUC5AC and MUC5B proteins compared with allergen-challenged wild-type mice. Impaired mucin production in Agr2(-/-) mice was accompanied by an increase in the proportion of mucins contained within the ER and by evidence of ER stress in airway epithelium. This study shows that AGR2 increases with mucin overproduction in individuals with asthma and in mouse models of allergic airway disease. AGR2 interacts with immature mucin in the ER and loss of AGR2 impairs allergen-induced MUC5AC and MUC5B overproduction.

  2. Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells

    PubMed Central

    Kreda, Silvia M; Okada, Seiko F; van Heusden, Catharina A; O'Neal, Wanda; Gabriel, Sherif; Abdullah, Lubna; Davis, C William; Boucher, Richard C; Lazarowski, Eduardo R

    2007-01-01

    The efficiency of the mucociliary clearance (MCC) process that removes noxious materials from airway surfaces depends on the balance between mucin secretion, airway surface liquid (ASL) volume, and ciliary beating. Effective mucin dispersion into ASL requires salt and water secretion onto the mucosal surface, but how mucin secretion rate is coordinated with ion and, ultimately, water transport rates is poorly understood. Several components of MCC, including electrolyte and water transport, are regulated by nucleotides in the ASL interacting with purinergic receptors. Using polarized monolayers of airway epithelial Calu-3 cells, we investigated whether mucin secretion was accompanied by nucleotide release. Electron microscopic analyses of Calu-3 cells identified subapical granules that resembled goblet cell mucin granules. Real-time confocal microscopic analyses revealed that subapical granules, labelled with FM 1-43 or quinacrine, were competent for Ca2+-regulated exocytosis. Granules containing MUC5AC were apically secreted via Ca2+-regulated exocytosis as demonstrated by combined immunolocalization and slot blot analyses. In addition, Calu-3 cells exhibited Ca2+-regulated apical release of ATP and UDP-glucose, a substrate of glycosylation reactions within the secretory pathway. Neither mucin secretion nor ATP release from Calu-3 cells were affected by activation or inhibition of the cystic fibrosis transmembrane conductance regulator. In SPOC1 cells, an airway goblet cell model, purinergic P2Y2 receptor-stimulated increase of cytosolic Ca2+ concentration resulted in secretion of both mucins and nucleotides. Our data suggest that nucleotide release is a mechanism by which mucin-secreting goblet cells produce paracrine signals for mucin hydration within the ASL. PMID:17656429

  3. Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells.

    PubMed

    Kreda, Silvia M; Okada, Seiko F; van Heusden, Catharina A; O'Neal, Wanda; Gabriel, Sherif; Abdullah, Lubna; Davis, C William; Boucher, Richard C; Lazarowski, Eduardo R

    2007-10-01

    The efficiency of the mucociliary clearance (MCC) process that removes noxious materials from airway surfaces depends on the balance between mucin secretion, airway surface liquid (ASL) volume, and ciliary beating. Effective mucin dispersion into ASL requires salt and water secretion onto the mucosal surface, but how mucin secretion rate is coordinated with ion and, ultimately, water transport rates is poorly understood. Several components of MCC, including electrolyte and water transport, are regulated by nucleotides in the ASL interacting with purinergic receptors. Using polarized monolayers of airway epithelial Calu-3 cells, we investigated whether mucin secretion was accompanied by nucleotide release. Electron microscopic analyses of Calu-3 cells identified subapical granules that resembled goblet cell mucin granules. Real-time confocal microscopic analyses revealed that subapical granules, labelled with FM 1-43 or quinacrine, were competent for Ca(2+)-regulated exocytosis. Granules containing MUC5AC were apically secreted via Ca(2+)-regulated exocytosis as demonstrated by combined immunolocalization and slot blot analyses. In addition, Calu-3 cells exhibited Ca(2+)-regulated apical release of ATP and UDP-glucose, a substrate of glycosylation reactions within the secretory pathway. Neither mucin secretion nor ATP release from Calu-3 cells were affected by activation or inhibition of the cystic fibrosis transmembrane conductance regulator. In SPOC1 cells, an airway goblet cell model, purinergic P2Y(2) receptor-stimulated increase of cytosolic Ca(2+) concentration resulted in secretion of both mucins and nucleotides. Our data suggest that nucleotide release is a mechanism by which mucin-secreting goblet cells produce paracrine signals for mucin hydration within the ASL.

  4. Analysis of mucosal mucins separated by SDS-urea agarose polyacrylamide composite gel electrophoresis.

    PubMed

    Issa, Samah M A; Schulz, Benjamin L; Packer, Nicolle H; Karlsson, Niclas G

    2011-12-01

    Efficient separation of mucins (200 kDa-2 MDa) was demonstrated using gradient SDS agarose/polyacrylamide composite gel electrophoresis (SDS-AgPAGE). Inclusion of urea (SDS-UAgPAGE) in the gels casting were shown to have no effect on the migration of mucins in the gel and allowed casting of gel at room temperature. This simplified the procedure for multiple casting of agarose polyacrylamide gradients and increased reproducibility of these gels. Hence, the implementation of urea makes the technique applicable for high throughput isolation and screening of mucin oligosaccharides by LC-MS after releasing the oligosaccharides from isolated, blotted mucin subpopulations. It was also shown that the urea addition had no effect on other supporting applications such as western and lectin blotting. In addition, identification of the mucin protein after tryptic digestion and LC-MS was possible and no protein carbamylation due to the presence of urea in the gel was detected. LC-MS software developed for metabolomic analysis was used for O-linked oligosaccharide detection and differential display of various mucin samples. Using this method, heterogeneous glycosylation of mucins and mucin-type molecules isolated by SDS-AgPAGE and SDS-UAgPAGE was shown to consist of more than 80 different components in a single band, and in the extreme cases, up to 300-500 components (MUC5B/AC from saliva and sputum and). Metabolomic software was also used to show that the migration of mucin isoforms within the gel is due to heterogeneous size distribution of the oligosaccharides, with the slower migrating bands enriched in high-molecular-weight oligosaccharides.

  5. The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting.

    PubMed

    Jonckheere, Nicolas; Vasseur, Romain; Van Seuningen, Isabelle

    2017-03-01

    RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence. In this review, we discuss the central role of K-RAS mutations and their tremendous diversity of biological properties by the interconnected regulation of signaling pathways (MAPKs, NF-κB, PI3K, Ral…). In pancreatic ductal adenocarcinoma, transcriptome analysis and preclinical animal models showed that K-RAS mutation alters biological behavior of PDAC cells (promoting proliferation, migration and invasion, evading growth suppressors, regulating mucin pattern, and miRNA expression). K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming. Finally we discuss therapeutic targeting strategies of K-RAS that have been developed without significant clinical success so far. As K-RAS is considered as the undruggable target, targeting its multiple effectors and target genes should be considered as potential alternatives.

  6. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    PubMed Central

    Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  7. Refractory Jaundice From Intraductal Papillary Mucinous Neoplasm Treated With Cholangioscopy-Guided Radiofrequency Ablation.

    PubMed

    Brown, Nicholas G; Camilo, Joel; McCarter, Martin; Shah, Raj J

    2016-04-01

    Intraductal papillary mucinous neoplasms (IPMNs) are epithelial neoplasms treated with surgical resection when appropriate. We present a 79-year-old man with jandice refractory to endoscopic stenting. Biliary radiofrequency ablation (RFA) with cholangioscopy was used as palliation of obstructive jaundice due to a mucin-producing pancreatic IPMN with fistulous biliary communication. Clinical improvement permitted surgery, and he returned to pre-illness status at 17 months. The use of cholangioscopy in the setting of mucinous filling defects can guide over-the-wire RFA for palliation and may be a bridge to surgery.

  8. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  9. Adenocarcinoma - chest x-ray (image)

    MedlinePlus

    This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung (left side ... density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and ...

  10. Aeromonas salmonicida Binds Differentially to Mucins Isolated from Skin and Intestinal Regions of Atlantic Salmon in an N-Acetylneuraminic Acid-Dependent Manner

    PubMed Central

    Padra, János T.; Sundh, Henrik; Jin, Chunsheng; Karlsson, Niclas G.; Sundell, Kristina

    2014-01-01

    Aeromonas salmonicida subsp. salmonicida infection, also known as furunculosis disease, is associated with high morbidity and mortality in salmonid aquaculture. The first line of defense the pathogen encounters is the mucus layer, which is predominantly comprised of secreted mucins. Here we isolated and characterized mucins from the skin and intestinal tract of healthy Atlantic salmon and studied how A. salmonicida bound to them. The mucins from the skin, pyloric ceca, and proximal and distal intestine mainly consisted of mucins soluble in chaotropic agents. The mucin density and mucin glycan chain length from the skin were lower than were seen with mucin from the intestinal tract. A. salmonicida bound to the mucins isolated from the intestinal tract to a greater extent than to the skin mucins. The mucins from the intestinal regions had higher levels of sialylation than the skin mucins. Desialylating intestinal mucins decreased A. salmonicida binding, whereas desialylation of skin mucins resulted in complete loss of binding. In line with this, A. salmonicida also bound better to mammalian mucins with high levels of sialylation, and N-acetylneuraminic acid appeared to be the sialic acid whose presence was imperative for binding. Thus, sialylated structures are important for A. salmonicida binding, suggesting a pivotal role for sialylation in mucosal defense. The marked differences in sialylation as well as A. salmonicida binding between the skin and intestinal tract suggest interorgan differences in the host-pathogen interaction and in the mucin defense against A. salmonicida. PMID:25287918

  11. Ice Giant Exploration

    NASA Astrophysics Data System (ADS)

    Rymer, A. M.; Arridge, C. S.; Masters, A.; Turtle, E. P.; Simon, A. A.; Hofstadter, M. D.; Turrini, D.; Politi, R.

    2015-12-01

    The Ice Giants in our solar system, Uranus and Neptune, are fundamentally different from their Gas Giant siblings Jupiter and Saturn, from the different proportions of rock and ice to the configuration of their planetary magnetic fields. Kepler space telescope discoveries of exo-planets indicate that planets of this type are among the most ubiquitous universally and therefore a future mission to explore the nature of the Ice Giants in our own solar system will provide insights into the nature of extra-solar system objects in general. Uranus has the smallest self- luminosity of all the planets, potentially related to catastrophic events early in the planet's history, which also may explain Uranus' large obliquity. Uranus' atmosphere is subject to extreme seasonal forcing making it unique in the Solar System. Neptune is also unique in a number of ways, notably its large moon Triton which is likely a captured Kuiper Belt Object and one of only two moons in the solar system with a robustly collisional atmosphere. Similar to Uranus, the angle between the solar wind and the magnetic dipole axis is subject to large-amplitude variations on both diurnal and seasonal timescales, but peculiarly it has one of the quietest magnetospheres of the solar system, at least according to Voyager 2, the only spacecraft to encounter Neptune to date. A comprehensive mission, as advocated in the Decadal Survey, would provide enormous science return but is also challenging and expensive. In this presentation we will discuss mission scenarios and suggest how collaboration between disciplines and internationally can help us to pursue a mission that includes Ice Giant exploration.

  12. Giant cell arteritis

    PubMed Central

    Calvo-Romero, J

    2003-01-01

    Giant cell arteritis (GCA), temporal arteritis or Horton's arteritis, is a systemic vasculitis which involves large and medium sized vessels, especially the extracranial branches of the carotid arteries, in persons usually older than 50 years. Permanent visual loss, ischaemic strokes, and thoracic and abdominal aortic aneurysms are feared complications of GCA. The treatment consists of high dose steroids. Mortality, with a correct treatment, in patients with GCA seems to be similar that of controls. PMID:13679546

  13. Giant Cell Arteritis.

    PubMed

    Hoffman, Gary S

    2016-11-01

    This issue provides a clinical overview of giant cell arteritis, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  14. Mucin-like peptides from Echinococcus granulosus induce antitumor activity.

    PubMed

    Noya, Verónica; Bay, Sylvie; Festari, María Florencia; García, Enrique P; Rodriguez, Ernesto; Chiale, Carolina; Ganneau, Christelle; Baleux, Françoise; Astrada, Soledad; Bollati-Fogolín, Mariela; Osinaga, Eduardo; Freire, Teresa

    2013-09-01

    There is substantial evidence suggesting that certain parasites can have antitumor properties. We evaluated mucin peptides derived from the helminth Echinococcus granulosus (denominated Egmuc) as potential inducers of antitumor activity. We present data showing that Egmuc peptides were capable of inducing an increase of activated NK cells in the spleen of immunized mice, a fact that was correlated with the capacity of splenocytes to mediate killing of tumor cells. We demonstrated that Egmuc peptides enhance LPS-induced maturation of dendritic cells in vitro by increasing the production of IL-12p40p70 and IL-6 and that Egmuc-treated DCs may activate NK cells, as judged by an increased expression of CD69. This evidence may contribute to the design of tumor vaccines and open new horizons in the use of parasite-derived molecules in the fight against cancer.

  15. Optimal design for studying mucoadhesive polymers interaction with gastric mucin using a quartz crystal microbalance with dissipation (QCM-D): Comparison of two different mucin origins.

    PubMed

    Oh, Sejin; Wilcox, Matthew; Pearson, Jeffrey P; Borrós, Salvador

    2015-10-01

    The objective of this present study was to develop an efficient and simple method, based on the use of a quartz crystal microbalance with dissipation (QCM-D), to evaluate the mucoadhesive characteristics of cationic polymers; chitosan, thiolated chitosan (chitosan-SH), and polyallylamine hydrochloride (PAH), and anionic polymers; hyaluronic acid (HA) and thiolated hyaluronic acid (HA-SH). The experiments were carried out at pH 4 to assess the interaction between mucoadhesive polymers and a mucin-coated gold surface. A key point in the QCM-D protocol development was to evaluate two sources of mucin: native porcine gastric mucin (NPGM) and commercially available porcine gastric mucin (CPGM). QCM-D has shown its potential as a highly sensitive technique that provides information about the interaction of mucoadhesive polymers with gastric mucin. The technique would allow the classification of these polymers in order to further assess their application as base materials for nanocarriers, designed to interact with the mucosal barrier which represents a stumbling block for drug adsorption.

  16. Structures of sulfated oligosaccharides in human trachea mucin glycoproteins.

    PubMed

    Sangadala, S; Bhat, U R; Mendicino, J

    1993-09-08

    The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. Only one in about every 10 repeating units contained sulfate esters. Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains.

  17. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    ClinicalTrials.gov

    2017-04-10

    Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bladder Adenocarcinoma; Bronchioloalveolar Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Dermoid Cyst; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm

  18. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.

    PubMed

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni; Roslind, Anne; Giese, Nathalia; Horn, Thomas; Wøjdemann, Morten; Johansen, Julia S

    2012-12-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic

  19. Strategies for screening for pancreatic adenocarcinoma in high-risk patients.

    PubMed

    Canto, Marcia Irene

    2007-08-01

    Identification of high-risk individuals, genetic counseling, and informed consent are important components of a screening program for familial pancreatic cancer. Screening high-risk individuals with imaging tests, such endoscopic ultrasound (EUS) and computed tomography (CT), can lead to the detection and treatment of predominantly asymptomatic early pancreatic neoplasms, as well as extra-pancreatic tumors. These pancreatic neoplasms consist of resectable, mostly branch-type non-invasive intraductal papillary mucinous neoplasms (IPMNs). EUS can visualize these very early IPMNs as focal duct ectasias or cysts. EUS features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to multifocal pancreatic intraepithelial neoplasia (PanIN). No one molecular marker is ready for "prime time" screening of high-risk individuals. Translational studies are underway to discover novel biomarkers for IPMNs, PanIN-3 lesions, or microinvasive adenocarcinoma, which are likely to be cured by timely intervention. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic neoplasia and timely intervention results in decreased pancreatic cancer incidence and mortality in high-risk individuals.

  20. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition.

    PubMed

    Mukherjee, Pinku; Basu, Gargi D; Tinder, Teresa L; Subramani, Durai B; Bradley, Judy M; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2009-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E(2) and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.

  1. MUC13 Interaction with Receptor Tyrosine Kinase HER2 Drives Pancreatic Ductal Adenocarcinoma Progression

    PubMed Central

    Khan, Sheema; Sikander, Mohammed; Ebeling, Mara C.; Ganju, Aditya; Kumari, Sonam; Yallapu, Murali M.; Hafeez, Bilal Bin; Ise, Tomoko; Nagata, Satoshi; Zafar, Nadeem; Behrman, Stephen W.; Wan, Jim Y.; Ghimire, Hemendra M.; Sahay, Peeyush; Pradhan, Prabhakar; Chauhan, Subhash C.; Jaggi, Meena

    2016-01-01

    Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade including, ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility and invasion of PDAC cells - all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC. PMID:27321183

  2. Nanomaterial-protein interactions: the case of pristine and functionalized carbon nanotubes and porcine gastric mucin

    NASA Astrophysics Data System (ADS)

    Barbero, Nadia; Marenchino, Marco; Campos-Olivas, Ramón; Oliaro-Bosso, Simonetta; Bonandini, Luca; Boskovic, Jasminka; Viscardi, Guido; Visentin, Sonja

    2016-04-01

    Mucus represents a serious obstacle that prevents the penetration of drug carrier's transport across the mucus barrier. This study highlights the interaction between mucin glycoprotein, mucin from porcine stomach Type III (PGM) and different pristine and functionalized single-wall and multi-wall carbon nanotubes (CNTs), under physiological conditions, in order to investigate the affinity of different CNTs to mucin. This aspect could be of the utmost importance for the use of CNTs for biomedical purposes. The interaction between CNTs and PGM was investigated by using different techniques like fluorescence steady-state spectroscopy, thermogravimetric analysis (TGA), dynamic light scattering (DLS), circular dichroism (CD), electrophoresis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). We demonstrated that mucin has impressive capabilities for binding CNTs in physiological solutions. Moreover, we proved that the nanomaterial-protein interaction is influenced by the different natures of the tubes (SW and MW) and by their different functionalizations (pristine and oxidized CNTs).

  3. Subunit structure of deglycosylated human and swine trachea and Cowper's gland mucin glycoproteins.

    PubMed

    Sangadala, S; Kim, D; Brewer, J M; Mendicino, J

    1991-03-27

    The oligosaccharide chains in human and swine trachea and Cowper's gland mucin glycoproteins were completely removed in order to examine the subunit structure and properties of the polypeptide chains of these glycoproteins. The carbohydrate, which constitutes more than 70% of these glycoproteins, was removed by two treatments with trifluoromethanesulfonic acid for 3 h at 3 degrees and periodate oxidation by a modified Smith degradation. All of the sialic acid, fucose, galactose, N-acetylglucosamine and N-acetylgalactosamine present in these glycoproteins was removed by these procedures. The deglycosylated polypeptide chains were purified and characterized. The size of the monomeric forms of all three polypeptide chains were very similar. Data obtained by gel filtration, release of amino acids during hydrolysis with carboxypeptidase B and gel electrophoresis in the presence of 0.1% dodecyl sulfate showed that a major fraction from each of the three mucin glycoproteins had a molecular size of about 67 kDa. All of the deglycosylated chains had a tendency to aggregate. Digestion with carboxypeptidases showed that human and swine trachea mucin glycoproteins had identical carboxyl terminal sequences, -Val-Ala-Phe-Tyr-Leu-Lys-Arg-COOH. Cowper's gland mucin glycoprotein had a similar carboxyl terminal sequence, -Val-Ala-Tyr-Leu-Phe-Arg-Arg-COOH. The yield of amino acids after long periods of hydrolysis with carboxypeptidases showed that at least 85% of the polypeptide chains in each of the deglycosylated preparations have these sequences. These results suggested that the polypeptide chains in these deglycosylated mucin glycoprotein preparations were relatively homogeneous. The deglycosylated polypeptide chains as well as the intact mucin glycoproteins had blocked amino terminii. The purified polypeptide chains were digested with trypsin-TCPK, and S. aureus V8 protease and the resulting peptides were isolated by gel electrophoresis in the presence of 0.1% dodecyl sulfate

  4. Precursor lesions of mucinous carcinoma of the breast: analysis of 130 cases.

    PubMed

    Kryvenko, Oleksandr N; Chitale, Dhananjay A; Yoon, Jiyoon; Arias-Stella, Javier; Meier, Frederick A; Lee, Min W

    2013-07-01

    Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P<0.05). In summary, mucinous DCIS is a precursor to MC with distinctive features that link patterns of DCIS with aggressive MC phenotypes. The 2 observed transitions between mucinous DCIS and MC suggest that

  5. A huge ovarian mucinous cystadenoma causing virilization, preterm labor, and persistent supine hypotensive syndrome during pregnancy

    PubMed Central

    Acar, Canan; Temizkan, Osman; Ozagari, Aysim; Gozukara, Ilay; Akyol, Atif

    2016-01-01

    Mucinous cystadenoma (MC) of the ovary is an unilateral, multilocular cystic benign epithelial tumor. Supposed to be hormone responsive, MC reaches huge sizes during pregnancy. Aortocaval compression is common during pregnancy, especially when the pregnant woman is in the supine position. However, the compression recovers with a change in position. The authors report the first case of a huge mucinous cystadenoma of the ovary complicating pregnancy and causing virilization, premature labor, and persistent supine hypotensive syndrome. PMID:27547742

  6. Single molecule study of heterotypic interactions between mucins possessing the Tn cancer antigen

    PubMed Central

    Haugstad, Kristin E; Stokke, Bjørn T; Brewer, C Fred; Gerken, Thomas A; Sletmoen, Marit

    2015-01-01

    Mucins are linear, heavily O-glycosylated proteins with physiological roles that include cell signaling, cell adhesion, inflammation, immune response and tumorgenesis. Cancer-associated mucins often differ from normal mucins by presenting truncated carbohydrate chains. Characterization of the binding properties of mucins with truncated carbohydrate side chains could thus prove relevant for understanding their role in cancer mechanisms such as metastasis and recognition by the immune system. In this work, heterotypic interactions of model mucins that possess the Tn (GalNAcαThr/Ser) and T (Galβ1–3GalNAcαThr/Ser) cancer antigens derived from porcine submaxillary mucin (PSM) were studied using atomic force microscopy. PSM possessing only the Tn antigen (Tn-PSM) was found to bind to PSM analogs possessing a combination of T, Tn and STn antigens as well as biosynthetic analogs of the core 1 blood group A tetrasaccharide (GalNAcα1–3[Fucα1–2] Galβ1–3GalNAcαSer/Thr). The rupture forces for the heterotypic interactions ranged from 18– to 31 pN at a force-loading rate of ∼0.5 nN/s. The thermally averaged distance from the bound complex to the transition state (xβ) was estimated to be in the range 0.37–0.87 nm for the first barrier of the Bell Evans analysis and within 0.34–0.64 nm based on a lifetime analysis. These findings reveal that the binding strength and energy landscape for heterotypic interactions of Tn-PSM with the above mucins, resemble homotypic interactions of Tn-PSM. This suggests common carbohydrate epitope interactions for the Tn cancer antigen with the above mucin analogs, a finding that may be important to the role of the Tn antigen in cancer cells. PMID:25527429

  7. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  8. Biochemical characterization of rat colonic mucins secreted in response to Entamoeba histolytica.

    PubMed

    Tse, S K; Chadee, K

    1992-04-01

    Invasion of the colonic mucosa by Entamoeba histolytica trophozoites is preceded by colonic mucus depletion. The aim of our studies was to determine whether E. histolytica caused a differential secretion of mucin species in a rat colonic loop model. Mucus secretion in response to amoebae was followed by release of acid-precipitable 3H-glucosamine metabolically labelled glycoproteins and in vitro labelling of glycoprotein secretion with NaB3H4. The secretory response consisted of high-Mr goblet cell mucins and an increase in the secretion of low-Mr nonmucin glycoproteins as determined by Sepharose 4B column chromatography. High-Mr mucins subfractionated by Cellex-E (ECTEOLA) ion-exchange chromatography demonstrated a minor neutral and a major acidic mucin (greater than 98%) species. Marked differences between the neutral and acidic mucin species were indicated by immunogenicity and amino acid compositions. Thin-section histochemistry of rat colons confirmed secretion of neutral and acidic mucins in response to E. histolytica and demonstrated secretory activity from goblet cells from both the crypts and interglandular epithelium. E. histolytica mucus secretagogue activity was generalized and may function to deplete the host's protective mucus layer, facilitating invasion by the parasites.

  9. Tensile bond strength of a polymeric intra-buccal bioadhesive: the mucin role.

    PubMed

    Pedrazzi, V; Lara, E H; Dal Ciampo, J O; Panzeri, H

    2001-01-01

    The intra-bucal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose have been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934TM/magnesium stearate (HPMC/Cp/StMg), was developed with the sodium fluoride as an active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile strength. Swine buccal mucosa extracted immediately after animals' sacrifice was employed as a substrate for the physical trials to obtain 16 test bodies. Artificial saliva with or without mucin was used to involve the substrate/bioadhesive system sets during the trials. Artificial salivas viscosity were determined by means of Brookfield viscometer, and they showed 10.0 cP artificial saliva with mucin, and 7.5 cP artificial saliva without mucin. The tensile strength assays showed the following averages: 12.89 Pa for the group "artificial saliva with mucin", and 12.35 Pa for the group "without mucin". Statistical analysis showed no significant difference between the assays for both artificial salivas, and we can conclude that the variable mucin did not interfere with the bioadhesion process for the polymeric devices.

  10. Analysis of the Distribution of Mucins in Adult Human Gastric Mucosa and Its Functional Significance

    PubMed Central

    2016-01-01

    Introduction Mucins are complex composition of carbohydrates seen in the epithelial cells lining the gastrointestinal tract (GIT). Normal distribution of such mucins in different part of the GIT and its alteration in various inflammatory, benign and malignant lesions of GIT has aroused interest in the field of histochemistry. Aim By applying variety of histochemical techniques an attempt has been made to draw a map of mucin secretion by the different epithelial cell types in different parts of the stomach. Materials and Methods Fifty samples were taken each from different parts of the stomach like fundus, body and pylorus, from dissected fresh specimens (total of 150 specimens). Tissue samples were subjected for routine process and studied for histological and different histochemical staining. Results Mucin pattern in adult predominantly secretes neutral mucosubstances. Surface epithelium shows predominant neutral mucin while cardiac and gastric glands with foveolar cells show moderate amount. Sialomucin is present in a few cells of the surface epithelium, foveolar cells and in most of the mucous neck cells. Small amount of sialomucin and sulphomucin are found in surface epithelial foveolar cells while traces of sulphomucin are found in deep foveolar cells. Mucous neck cells secrete both sulphomucin and sialomucin. Conclusion Normal gastric mucosa adjacent to gastric ulcers and malignant tumours of stomach secretes mucins which differ histochemically and biochemically from that of normal. Early recognition of such changes could be useful in recognizing the different type of carcinomas and their prognosis. PMID:27042436

  11. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas.

    PubMed

    Matsumoto, Yuri; Miyamoto, Hiroshi; Fukuya, Akira; Nakamura, Fumika; Goji, Takahiro; Kitamura, Shinji; Kimura, Tetsuo; Okamoto, Koichi; Sogabe, Masahiro; Muguruma, Naoki; Shimada, Mitsuo; Bando, Yoshimi; Takayama, Tetsuji

    2017-04-01

    Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.

  12. Effect of hydration on structural and thermodynamic properties of pig gastric and bovine submaxillary gland mucins.

    PubMed

    Znamenskaya, Yana; Sotres, Javier; Engblom, Johan; Arnebrant, Thomas; Kocherbitov, Vitaly

    2012-04-26

    One of the essential functions of mucous gel is protection of tissues against dehydration. The effect of hydration on the structural and thermodynamic properties of pig gastric mucin (PGM) and bovine submaxillary gland mucin (BSM) have been studied using atomic force microscopy (AFM), sorption, and differential scanning calorimetry (DSC). The analysis of sorption isotherms shows the higher water sorption capacity of PGM compared to BSM at RH levels lower than about 78%. The value of the hydration enthalpy at zero water content at 25 °C for both biopolymers is about -20 kJ/mol. Glass transitions of BSM and PGM occur at RH levels between 60 and 70% for both mucins. AFM indicates the presence of a dumbbell structure as well as a fiber-like structure in PGM samples. The experimental volume of the dry dumbbell molecule obtained by AFM is 3140 ± 340 nm(3). Using DSC data, the amount of nonfreezing water was calculated to be about 0.51 g/g of PGM. The phase diagram of PGM demonstrates two regions of different Tg: dependent and independent of hydration levels. In particular, at mucin concentrations from 0 to 67 wt %, the glass transition occurs at a constant temperature of about -15 °C. At higher concentrations of mucin, Tg is increasing with increasing mucin concentrations.

  13. Molecular structure and rheological properties of short-side-chain heavily glycosylated porcine stomach mucin.

    PubMed

    Yakubov, Gleb E; Papagiannopoulos, Aristeidis; Rat, Elodie; Easton, Richard L; Waigh, Thomas A

    2007-11-01

    The current accepted model for high-molecular-weight gastric mucins of the MUC family is that they adopt a polydisperse coil conformation in bulk solutions. We develop this model using well-characterized highly purified porcine gastric mucin Orthana that is genetically close to the human MUC6 type. It has short side chains and low levels of sialic acid residues and includes minute amounts of cysteine residues that, if abundant, can be responsible for the self-polymerization of mucin. We have established that the mucin structure in bulk solutions corresponds to a daisy-chain random coil. Dynamic light scattering experiments probe the internal dynamics of globular subunits (individual daisies) at the approximately 9 nm length scale, whereas viscosity and light scattering measurements indicate that the size of the whole mucin chains is much larger, approximately 50 nm. The bulk viscosity (eta) scales with mucin concentration (c) in a manner similar to that found for short-side-chain synthetic comb polyelectrolytes and is characterized by a transition between semidilute (eta approximately c1/2) and entangled (eta approximately c3/2) regimes.

  14. Secreted and membrane-bound mucins and idiopathic peptic ulcer disease.

    PubMed

    Niv, Yaron; Boltin, Doron

    2012-01-01

    The incidence of Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID)-negative peptic ulcer disease has increased over the last two decades, especially in the Western world and in countries with low H. pylori infection rates. Idiopathic peptic ulcer disease is a recently described entity which relates to peptic ulcers not caused by H. pylori, NSAID/aspirin therapy, other ulcerogenic organisms and drugs, or other rare malignant and benign diseases. Structural and secreted mucins create the unstirred gastric mucus layer and maintain a stable pH above the gastric mucosa. This mucous layer prevents enzymatic attack by acid and pepsin. Inhibition of cyclooxygenase by NSAID and aspirin inhibits prostaglandin production, inhibits mucin and bicarbonate secretion, and exposes the mucosa to the toxic effects of acid and intragastric enzymes. There is also a complex relationship between H. pylori and different mucin subtypes which on one hand facilitates mucin invasion but on the other hand protects the gastric mucosa. Genetic and epigenetic changes in the mucin molecule may be responsible for idiopathic peptic ulcer disease, but this hypothesis must be further investigated. Herein, the mucin hypothesis of idiopathic peptic ulcer disease is explored.

  15. RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary.

    PubMed

    Ryland, Georgina L; Hunter, Sally M; Doyle, Maria A; Rowley, Simone M; Christie, Michael; Allan, Prue E; Bowtell, David D L; Gorringe, Kylie L; Campbell, Ian G

    2013-02-01

    Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts.

  16. Non-pancreatic retroperitoneal mucinous neoplasms and a discussion of the differential diagnosis

    PubMed Central

    Cobb, Camilla; Raza, Anwar Sultana

    2016-01-01

    Retroperitoneal mucinous neoplasms are common and have a wide range of differential diagnoses to consider. It is of utmost importance to maintain a multidisciplinary approach when evaluating these lesions. Clinical history, surgical impression and radiographic studies should be obtained and used in conjunction with morphology and immunohistochemistry to help guide the pathologist to the correct diagnosis. We recently encountered a case of a 51-year-old man who presented with an 11.5 cm left-sided retroperitoneal mucinous neoplasm. This lesion was initially diagnosed as a low-grade mucinous carcinoma of probable pancreatic origin at an outside facility, and he was subsequently treated with chemotherapy. One year later he presented to our institution and underwent retroperitoneal en bloc resection of the 7-cm residual multiloculated mucinous neoplasm. When discussed at tumor board additional medical history was obtained, and review of the patient’s chart revealed a remote history of left orchiectomy for a mixed malignant germ cell tumor and metastatic embryonal carcinoma in 2 of 34 retroperitoneal/para-aortic lymph nodes. With no clinical evidence of tumor in the pancreas or extension from it, the predominately para-aortic location of the tumor favors a mucinous carcinoma arising from a rest of mature metastatic/proliferating teratoma that persisted after chemotherapy. This case illustrates the importance of a thorough history, however remote, and correlation with imaging in the development of differential diagnoses, as well as, the need to consider non-pancreaticobiliary sources of retroperitoneal mucinous tumors. PMID:27034817

  17. Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.

    PubMed

    Deng, Yunte; Xue, Debin; Wang, Xiaoyan; Xu, Sanpeng; Ao, Qilin; Hu, Zhiyong; Wang, Guoping

    2012-06-01

    Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.

  18. Mucinous versus nonmucinous solitary pulmonary nodular bronchioloalveolar carcinoma: CT and FDG PET findings and pathologic comparisons.

    PubMed

    Lee, Ho Yun; Lee, Kyung Soo; Han, Joungho; Kim, Byung-Tae; Cho, Young-Seok; Shim, Young Mog; Kim, Jhingook

    2009-08-01

    We aimed to evaluate the CT, PET, and pathologic findings of solitary pulmonary nodular mucinous and nonmucinous bronchioloalveolar carcinomas (BACs). From August 2003 to March 2008, we saw 24 patients with solitary pulmonary nodular mucinous (n=6) or nonmucinous (n=18) BACs that were resected. CT and PET findings of the lesions were assessed in terms of size, solidity, morphologic characteristics, attenuation and maximum standardized uptake value (mSUV). All nonmucinous BACs appeared as a pure ground-glass opacity (GGO) nodule, whereas mucinous BACs appeared as solid (n=4) or part-solid (n=2) nodules. CT attenuation values were significantly higher for mucinous BACs (-21.0 HU+/-4.9) than for nonmucinous BACs (-491.8 HU+/-172.5) (P<.001). Mean mSUVs were 2.3+/-1.9 for mucinous BACs and 0.5+/-0.8 for nonmucinous BACs (P=.007), but mSUVs were not statistically different after size adjustment (r=0.371, P=.081). Mucinous BACs appear as solid or part-solid nodules at CT, whereas nonmucinous BACs present as pure GGO nodules. Both subtypes of tumors show scant FDG uptake at PET.

  19. Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

    PubMed Central

    Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

    2013-01-01

    Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

  20. Imaging Extrasolar Giant Planets

    NASA Astrophysics Data System (ADS)

    Bowler, Brendan P.

    2016-10-01

    High-contrast adaptive optics (AO) imaging is a powerful technique to probe the architectures of planetary systems from the outside-in and survey the atmospheres of self-luminous giant planets. Direct imaging has rapidly matured over the past decade and especially the last few years with the advent of high-order AO systems, dedicated planet-finding instruments with specialized coronagraphs, and innovative observing and post-processing strategies to suppress speckle noise. This review summarizes recent progress in high-contrast imaging with particular emphasis on observational results, discoveries near and below the deuterium-burning limit, and a practical overview of large-scale surveys and dedicated instruments. I conclude with a statistical meta-analysis of deep imaging surveys in the literature. Based on observations of 384 unique and single young (≈5-300 Myr) stars spanning stellar masses between 0.1 and 3.0 M ⊙, the overall occurrence rate of 5-13 M Jup companions at orbital distances of 30-300 au is {0.6}-0.5+0.7 % assuming hot-start evolutionary models. The most massive giant planets regularly accessible to direct imaging are about as rare as hot Jupiters are around Sun-like stars. Dividing this sample into individual stellar mass bins does not reveal any statistically significant trend in planet frequency with host mass: giant planets are found around {2.8}-2.3+3.7 % of BA stars, <4.1% of FGK stars, and <3.9% of M dwarfs. Looking forward, extreme AO systems and the next generation of ground- and space-based telescopes with smaller inner working angles and deeper detection limits will increase the pace of discovery to ultimately map the demographics, composition, evolution, and origin of planets spanning a broad range of masses and ages.

  1. Pancreatic Adenocarcinoma, Version 2.2012

    PubMed Central

    Tempero, Margaret A.; Arnoletti, J. Pablo; Behrman, Stephen W.; Ben-Josef, Edgar; Benson, Al B.; Casper, Ephraim S.; Cohen, Steven J.; Czito, Brian; Ellenhorn, Joshua D. I.; Hawkins, William G.; Herman, Joseph; Hoffman, John P.; Ko, Andrew; Komanduri, Srinadh; Koong, Albert; Ma, Wen Wee; Malafa, Mokenge P.; Merchant, Nipun B.; Mulvihill, Sean J.; Muscarella, Peter; Nakakura, Eric K.; Obando, Jorge; Pitman, Martha B.; Sasson, Aaron R.; Tally, Anitra; Thayer, Sarah P.; Whiting, Samuel; Wolff, Robert A.; Wolpin, Brian M.; Freedman-Cass, Deborah A.; Shead, Dorothy A.

    2013-01-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. PMID:22679115

  2. A Giant Urethral Calculus.

    PubMed

    Sigdel, G; Agarwal, A; Keshaw, B W

    2014-01-01

    Urethral calculi are rare forms of urolithiasis. Majority of the calculi are migratory from urinary bladder or upper urinary tract. Primary urethral calculi usually occur in presence of urethral stricture or diverticulum. In this article we report a case of a giant posterior urethral calculus measuring 7x3x2 cm in a 47 years old male. Patient presented with acute retention of urine which was preceded by burning micturition and dribbling of urine for one week. The calculus was pushed in to the bladder through the cystoscope and was removed by suprapubic cystolithotomy.

  3. Giant left ventricular pseudoaneurysm.

    PubMed

    Prakash, Sumi; Garg, Nadish; Xie, Gong-Yuan; Dellsperger, Kevin C

    2010-01-01

    Left ventricular (LV) pseudoaneurysm (PS) is an uncommon, often fatal complication associated with myocardial infarction, cardiothoracic surgery, trauma, and, rarely, infective endocarditis. A 28-year-old man with prior history of bioprosthetic mitral valve replacement presented with congestive heart failure and bacteremia with Abiotrophia granulitica. Transesophageal echocardiogram showed bioprosthesis dysfunction, large vegetations, mitral regurgitation, and probable PS. Cardiac and chest CT confirmed a PS communicating with the left ventricle Patient had pulseless electrical activity and died. Autopsy showed a giant PS with layered thrombus and pseudo-endothelialized cavity. Our case highlights the importance of multimodality imaging as an important tool in management of PS.

  4. [Atypical metastatic site of lung adenocarcinoma].

    PubMed

    Sakhri, L; Mennecier, B; Jacqmin, D; Di Marco, A; Schumacher, C; Chenard, M-P; Bergmann, E; Quoix, E

    2011-12-01

    The case concerns a 40 years old smoker male, treated for an adenocarcinoma of the left upper lobe, metastatic in muscle extended to the right femur cortex. The patient had first a surgical excision of the mass of the thigh, an intramedullary femoral nailing, and six courses of chemotherapy (cisplatin-vinorelbine) with concurrent thoracic radiotherapy. This treatment led to disease stability. One year later, hematuria revealed a bladder tumor. Cystoscopy with biopsy concluded to an adenocarcinoma pulmonary origin. The PET-scanner showed an uptake of the bladder mass, a hypermetabolic right adrenal gland and subcutaneous left shoulder nodule. The patient had a partial cystectomy associated with enterocystoplasty and left ureteral reimplantation, plus excision of the subcutaneous nodule located in the left shoulder and a right adrenalectomy during the same time. All of the sites were metastasis from adenocarcinoma of pulmonary origin. A salvage chemotherapy was initiated. In the vast majority of cases, bladder metastasis as primary bladder tumours is revealed by hematuria, cystitis or sometimes vague pelvic pain. Our case is a very unusual bladder metastatic site from lung cancer. We will discuss the different procedures and the therapeutic strategies on the basis of the published data.

  5. Laparoscopy in the management of gastric adenocarcinoma.

    PubMed Central

    Burke, E C; Karpeh, M S; Conlon, K C; Brennan, M F

    1997-01-01

    OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy. Images Figure 4. PMID:9060581

  6. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

    PubMed Central

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-01-01

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. PMID:24084722

  7. Intraoperative molecular imaging to identify lung adenocarcinomas

    PubMed Central

    Newton, Andrew D.; Kennedy, Gregory T.; Predina, Jarrod D.; Low, Philip S.

    2016-01-01

    Intraoperative molecular imaging is a promising new technology with numerous applications in lung cancer surgery. Accurate identification of small nodules and assessment of tumor margins are two challenges in pulmonary resections for cancer, particularly with increasing use of video-assisted thoracoscopic surgery (VATS). One potential solution to these problems is intraoperative use of a fluorescent contrast agent to improve detection of cancer cells. This technology requires both a targeted fluorescent dye that will selectively accumulate in cancer cells and a specialized imaging system to detect the cells. In several studies, we have shown that intraoperative imaging with indocyanine green (ICG) can be used to accurately identify indeterminate pulmonary nodules. The use of a folate-tagged fluorescent molecule targeted to the folate receptor-α (FRα) further improves the sensitivity and specificity of detecting lung adenocarcinomas. We have demonstrated this technology can be used as an “optical biopsy” to differentiate adenocarcinoma versus other histological subtypes of pulmonary nodules. This strategy has potential applications in assessing bronchial stump margins, identifying synchronous or metachronous lesions, and rapidly assessing lymph nodes for lung adenocarcinoma. PMID:28066672

  8. Comprehensive molecular profiling of lung adenocarcinoma

    PubMed Central

    2014-01-01

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. PMID:25079552

  9. Comprehensive molecular profiling of lung adenocarcinoma.

    PubMed

    2014-07-31

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

  10. Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects

    PubMed Central

    2014-01-01

    Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1–2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as

  11. Solitary Psoas Muscle Metastasis of Gastroesphageal Junction Adenocarcinoma

    PubMed Central

    Azadeh, Payam; Yaghobi Joybari, Ali; Sarbaz, Samaneh; Ghiasi, Hosein Ali; Farasatinasab, Maryam

    2016-01-01

    Metastasis of gastroesphageal junction (GEJ) adenocarcinoma in skeletal muscle is rare and primary sites for skeletal muscle metastases are usually lung, renal and colorectal cancer. We have encountered with the first case report of solitary psoas muscle metastasis of GEJ adenocarcinoma. Here we describe a 65 years old man was diagnosed with GEJ adenocarcinoma in Gastroenterology Department, Imam Hussein Hospital, Tehran, Iran in February 2014. We were not able to use PET techniques due to lack of access. Staging CT scans demonstrated a small mass lateral to right psoas muscle. A CT-guided core needle biopsy of right psoas muscle was performed that supported a diagnosis of adenocarcinoma consistent with primary adenocarcinoma of the GEJ. Distant metastasis to skeletal muscle rarely occurs in patients with GEJ adenocarcinoma, but heightened awareness to these soft tissue lesions is warranted. CT or MR imaging could show findings suggestive of metastatic disease, although PET is preferable modality. PMID:26870148

  12. Giant papillary conjunctivitis.

    PubMed Central

    Donshik, P C

    1994-01-01

    Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 11 A FIGURE 11 B FIGURE 11 C FIGURE 11 D PMID:7886881

  13. Giant extragenital Bowen's disease.

    PubMed

    Bakardzhiev, Ilko; Chokoeva, Anastasiya Atanasova; Tchernev, Georgi

    2015-12-01

    Giant extragenital forms of Morbus Bowen are extremely rare. The already described cases in the word literature are most commonly with periungual localization, as well as located on the foot and neck area. The clinical manifestation is presented most commonly by non-specific erythematous to erythematous-squamous plaques or papules, which is confusing to the clinician. From the pathogenic point of view, it is important to be confirmed or rejected the presence of human papilloma viruses (HPVs) in each case of affected patient, as this information is mandatory in respect to the adequate selection of the subsequent regimen. If HPVs are detected, systemic antiviral therapy could be initiated to reduce the size of the lesions before subsequent surgical eradication. A postoperative prevention through vaccination could be also considered additionally. In cases of HPV-negative giant extragenital forms of Morbus Bowen (as in the described patient), the focus should be on local immunomodulation by substances such as imiquimod, which reduce the size of the lesions, thereby creating optimal opportunities for their future surgical eradication. Other possible options described in the literature include topical application of 5-fluorouracil, photodynamic therapy, cryotherapy, and laser therapy (carbon dioxide laser). The choice of the most appropriate regimen should have been an individual decision of the clinician, considering also the location and the extent of the lesion.

  14. Gas Giants Form Quickly

    NASA Technical Reports Server (NTRS)

    2007-01-01

    This is an artist's concept of a hypothetical 10-million-year-old star system. The bright blur at the center is a star much like our sun. The other orb in the image is a gas-giant planet like Jupiter. Wisps of white throughout the image represent traces of gas.

    Astronomers using NASA's Spitzer Space Telescope have found evidence showing that gas-giant planets either form within the first 10 million years of a sun-like star's life, or not at all. The lifespan for sun-like stars is about 10 billion years.

    The scientists came to this conclusion after searching for traces of gas around 15 different sun-like stars, most with ages ranging from 3 million to 30 million years. With the help of Spitzer's Infrared Spectrometer instrument, they were able to search for relatively warm gas in the inner regions of these star systems, an area comparable to the zone between Earth and Jupiter in our own solar system. They also used ground-based radio telescopes to search for cooler gas in the outer regions of these systems, an area comparable to the zone around Saturn and beyond.

  15. Giant Intradiverticular Bladder Tumor

    PubMed Central

    Noh, Mohamad Syafeeq Faeez Md; Aziz, Ahmad Fuad Abdul; Ghani, Khairul Asri Mohd; Siang, Christopher Lee Kheng; Yunus, Rosna; Yusof, Mubarak Mohd

    2017-01-01

    Patient: Male, 74 Final Diagnosis: Giant intradiverticular bladder tumor with metastasis Symptoms: Hematuria Medication:— Clinical Procedure: — Specialty: Urology Objective: Rare disease Background: Intradiverticular bladder tumors are rare. This renders diagnosis of an intradiverticular bladder tumor difficult. Imaging plays a vital role in achieving the diagnosis, and subsequently staging of the disease. Case Report: A 74-year-old male presented to our center with a few months history of constitutional symptoms. Upon further history, he reported hematuria two months prior to presentation, which stopped temporarily, only to recur a few days prior to coming to the hospital. The patient admitted to having lower urinary tract symptoms. However, there was no dysuria, no sandy urine, and no fever. Palpation of his abdomen revealed a vague mass at the suprapubic region, which was non tender. In view of his history and the clinical examination findings, an ultrasound of the abdomen and computed tomography (CT) was arranged. These investigations revealed a giant tumor that seemed to be arising from a bladder diverticulum, with a mass effect and hydronephrosis. He later underwent operative intervention. Conclusions: Intradiverticular bladder tumors may present a challenge to the treating physician in an atypical presentation; thus requiring a high index of suspicion and knowledge of tumor pathophysiology. As illustrated in our case, CT with its wide availability and multiplanar imaging capabilities offers a useful means for diagnosis, disease staging, operative planning, and follow-up. PMID:28246375

  16. Virulent Shigella flexneri Affects Secretion, Expression, and Glycosylation of Gel-Forming Mucins in Mucus-Producing Cells

    PubMed Central

    Sperandio, Brice; Fischer, Natalie; Chevalier-Curt, Marie Joncquel; Rossez, Yannick; Roux, Pascal; Robbe Masselot, Catherine

    2013-01-01

    Mucin glycoproteins are secreted in large amounts by the intestinal epithelium and constitute an efficient component of innate immune defenses to promote homeostasis and protect against enteric pathogens. In this study, our objective was to investigate how the bacterial enteropathogen Shigella flexneri, which causes bacillary dysentery, copes with the mucin defense barrier. We report that upon in vitro infection of mucin-producing polarized human intestinal epithelial cells, virulent S. flexneri manipulates the secretion of gel-forming mucins. This phenomenon, which is triggered only by virulent strains, results in accumulation of mucins at the cell apical surface, leading to the appearance of a gel-like structure that favors access of bacteria to the cell surface and the subsequent invasion process. We identify MUC5AC, a gel-forming mucin, as a component of this structure. Formation of this gel does not depend on modifications of electrolyte concentrations, induction of trefoil factor expression, endoplasmic reticulum stress, or response to unfolded proteins. In addition, transcriptional and biochemical analyses of infected cells reveal modulations of mucin gene expression and modifications of mucin glycosylation patterns, both of which are induced by virulent bacteria in a type III secretion system-dependent manner. Thus, S. flexneri has developed a dedicated strategy to alter the mucus barrier by targeting key elements of the gel-forming capacity of mucins: gene transcription, protein glycosylation, and secretion. PMID:23876800

  17. Reinflating Giant Planets

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-01-01

    Two new, large gas-giant exoplanets have been discovered orbiting close to their host stars. A recent study examining these planets and others like them may help us to better understand what happens to close-in hot Jupiters as their host stars reach the end of their main-sequence lives.OversizedGiantsUnbinned transit light curves for HAT-P-65b. [Adapted from Hartman et al. 2016]The discovery of HAT-P-65b and HAT-P-66b, two new transiting hot Jupiters, is intriguing. These planets have periods of just under 3 days and masses of roughly 0.5 and 0.8 times that of Jupiter, but their sizes are whats really interesting: they have inflated radii of 1.89 and 1.59 times that of Jupiter.These two planets, discovered using the Hungarian-made Automated Telescope Network (HATNet) in Arizona and Hawaii, mark the latest in an ever-growing sample of gas-giant exoplanets with radii larger than expected based on theoretical planetary structure models.What causes this discrepancy? Did the planets just fail to contract to the expected size when they were initially formed, or were they reinflated later in their lifetimes? If the latter, how? These are questions that scientists are only now starting to be able to address using statistics of the sample of close-in, transiting planets.Unbinned transit light curves for HAT-P-66b. [Hartman et al. 2016]Exploring Other PlanetsLed by Joel Hartman (Princeton University), the team that discovered HAT-P-65b and HAT-P-66b has examined these planets observed parameters and those of dozens of other known close-in, transiting exoplanets discovered with a variety of transiting exoplanet missions: HAT, WASP, Kepler, TrES, and KELT. Hartman and collaborators used this sample to draw conclusions about what causes some of these planets to have such large radii.The team found that there is a statistically significant correlation between the radii of close-in giant planets and the fractional ages of their host stars (i.e., the stars age divided by its full

  18. Allometry indicates giant eyes of giant squid are not exceptional

    PubMed Central

    2013-01-01

    Background The eyes of giant and colossal squid are among the largest eyes in the history of life. It was recently proposed that sperm whale predation is the main driver of eye size evolution in giant squid, on the basis of an optical model that suggested optimal performance in detecting large luminous visual targets such as whales in the deep sea. However, it is poorly understood how the eye size of giant and colossal squid compares to that of other aquatic organisms when scaling effects are considered. Results We performed a large-scale comparative study that included 87 squid species and 237 species of acanthomorph fish. While squid have larger eyes than most acanthomorphs, a comparison of relative eye size among squid suggests that giant and colossal squid do not have unusually large eyes. After revising constants used in a previous model we found that large eyes perform equally well in detecting point targets and large luminous targets in the deep sea. Conclusions The eyes of giant and colossal squid do not appear exceptionally large when allometric effects are considered. It is probable that the giant eyes of giant squid result from a phylogenetically conserved developmental pattern manifested in very large animals. Whatever the cause of large eyes, they appear to have several advantages for vision in the reduced light of the deep mesopelagic zone. PMID:23418818

  19. Ductal Adenocarcinoma of the Prostate: A Case Report

    PubMed Central

    Hayashi, Yutaro; Kawahara, Takashi; Iwashita, Hiromichi; Shimokihara, Kota; Tsutsumi, Sohgo; Takamoto, Daiji; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-year-old male was referred to our hospital for the further examination of an elevated prostate-specific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate. PMID:28101029

  20. Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.

    PubMed

    Lee, Sheng-Huang; Chaung, Chen-Rong

    2008-09-01

    Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.

  1. Searching the Evolutionary Origin of Epithelial Mucus Protein Components—Mucins and FCGBP

    PubMed Central

    Lang, Tiange; Klasson, Sofia; Larsson, Erik; Johansson, Malin E. V.; Hansson, Gunnar C.; Samuelsson, Tore

    2016-01-01

    The gel-forming mucins are large glycosylated proteins that are essential components of the mucus layers covering epithelial cells. Using novel methods of identifying mucins based on profile hidden Markov models, we have found a large number of such proteins in Metazoa, aiding in their classification and allowing evolutionary studies. Most vertebrates have 5–6 gel-forming mucin genes and the genomic arrangement of these genes is well conserved throughout vertebrates. An exception is the frog Xenopus tropicalis with an expanded repertoire of at least 26 mucins of this type. Furthermore, we found that the ovomucin protein, originally identified in chicken, is characteristic of reptiles, birds, and amphibians. Muc6 is absent in teleost fish, but we now show that it is present in animals such as ghost sharks, demonstrating an early origin in vertebrate evolution. Public RNA-Seq data were analyzed with respect to mucins in zebrafish, frog, and chicken, thus allowing comparison in regard of tissue and developmental specificity. Analyses of invertebrate proteins reveal that gel-forming-mucin type of proteins is widely distributed also in this group. Their presence in Cnidaria, Porifera, and in Ctenophora (comb jellies) shows that these proteins were present early in metazoan evolution. Finally, we examined the evolution of the FCGBP protein, abundant in mucus and related to gel-forming mucins in terms of structure and localization. We demonstrate that FCGBP, ubiquitous in vertebrates, has a conserved N-terminal domain. Interestingly, this domain is also present as an N-terminal sequence in a number of bacterial proteins. PMID:27189557

  2. Mucin biosynthesis and secretion in tracheal epithelial cells in primary culture.

    PubMed Central

    Svitacheva, N; Davies, J R

    2001-01-01

    Density-gradient centrifugation of bovine tracheal epithelial cell extracts revealed a 'high-density' (1.48 g/ml) sialic-acid-rich population as well as a 'low-density' (1.42 g/ml) one that reacted more strongly with a periodate-Schiff (PAS) assay. The sialic-acid-rich mucins were oligomeric molecules containing disulphide- bond-linked subunits and large glycosylated domains, whereas the PAS-reactive component seemed to be smaller and 'monomeric'. Only the 'high-density' population was secreted from cells cultured for 5 days on plastic or a collagen type 1, Matrigel or Vitrogen substrate. Release was less from cells grown on plastic than from those on a substrate and the amount was unaffected by increasing the thickness of the collagen layer. For cells grown on collagen, the amount of the sialic-acid-rich mucin increased over 10 days, whereas the PAS-reactive component was largely absent after 24 h, which was consistent with an initial release of stored PAS-reactive molecules and synthesis of the sialic-acid-rich mucins de novo. Both [(3)H]proline and [(35)S]sulphate were poorly incorporated into mucins detected with the chemical assays but molecules with a higher buoyant density than that of either of the previously identified species were labelled with [(35)S]sulphate. The [(35)S]sulphate-labelled material yielded large trypsin-resistant fragments and contained O-linked glycans but was not affected by digestion with chondroitin ABC lyase or heparan sulphate lyase, suggesting that it is a mucin rather than a proteoglycan. [(35)S]Sulphate is thus a poor marker for the major oligomeric mucins produced by bovine tracheal epithelial cells but the radiolabel is incorporated into a heavily labelled mucin-like component. PMID:11115395

  3. Characterization of mucin glycoprotein-specific translation products from swine and human trachea, pancreas and colon.

    PubMed

    Sangadala, S; Wallace, P; Mendicino, J

    1991-07-24

    RNA was isolated from cultured swine trachea epithelial cells and mucus-secreting tumor cell lines from human pancreas, lung and colon by extraction with guanidine isothiocyanate. Poly(A)+mRNA rich fractions were purified by repeated chromatography on oligo (dT)-cellulose columns and they were translated in a cell-free rabbit reticulocyte system. Translation products labelled with 35S-methionine were isolated by immunoprecipitation with specific antibodies to the polypeptide chains of mucin glycoproteins and they were analyzed by SDS-PAGE and fluorography. A single principal polypeptide band of 67 kDa was found in all cases when the immunoprecipitates were washed with buffer containing bovine serum albumin and unlabeled deglycosylated mucin glycoprotein. The intensity of the 67 kDa band decreased when unlabeled deglycosylated mucin glycoprotein was added to the translation mixture before immunoprecipitation. Affinity purified monospecific antibodies elicited against chemically deglycosylated polypeptide chains of purified mucin glycoproteins from human and swine trachea and Cowper's gland were all equally effective in immunoprecipitating the 67 kDa translation product. Monospecific antibodies directed against the glycosylated and unglycosylated regions of the polypeptide chain yielded single bands with a molecular size of 67 kDa in each case. Peptide profiles obtained by digestion of the 67 kDa translation product with S. aureus V-8 protease were identical to those obtained with deglycosylated human and swine trachea mucin glycoproteins. These studies clearly demonstrate that the translation product of swine trachea and human lung, colon and pancreatic mucin glycoprotein gene is a single polypeptide chain of 67 kDa. The relative size and properties of the translation products synthesized with poly (A)+RNA isolated from mucus-secreting cells derived from three different tissues are similar to those of mucin glycoproteins purified directly from mucus secretions of

  4. The tyrosine phosphatase, SHP-1, is involved in bronchial mucin production during oxidative stress.

    PubMed

    Jang, Min Kyoung; Kim, Sae-Hoon; Lee, Ki-Young; Kim, Tae-Bum; Moon, Keun Ae; Park, Chan Sun; Bae, Yun Jeong; Zhu, Zhou; Moon, Hee-Bom; Cho, You Sook

    2010-02-26

    Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as asthma and Chronic obstructive pulmonary disease (COPD). Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292 carcinoma cells were transfected with specific siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with hydrogen peroxide (H(2)O(2)), and Mucin 5AC(MUC5AC) gene expression and mucin production were determined. Activation of p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated. N-acetylcysteine (NAC) was employed to determine whether antioxidants could block MUC5AC production. To establish the precise role of p38, mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H(2)O(2), compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of p38 MAPK led to suppression of MUC5AC mRNA expression. Notably, mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway mucin production through regulating oxidative stress.

  5. Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase.

    PubMed Central

    Colina, A R; Aumont, F; Deslauriers, N; Belhumeur, P; de Repentigny, L

    1996-01-01

    A zone of extracellular digestion of the mucin layer around Candida albicans blastoconidia was observed by transmission electron microscopy in the jejunum of mice inoculated intragastrically (G. T. Cole, K. R. Seshan, L. M. Pope, and R. J. Yancey, J. Med. Vet. Mycol. 26:173-185, 1988). This observation prompted the hypothesis that a putative mucinolytic enzyme(s) may contribute to the virulence of C. albicans by facilitating penetration of the mucus barrier and subsequent adherence to and invasion of epithelial cells. Mucinolytic activity was observed as zones of clearing around colonies of C. albicans LAM-1 grown on agarose containing yeast nitrogen base, glucose, and hog gastric mucin. In addition, concentrated culture filtrate obtained after growth for 24 h in yeast nitrogen base, supplemented with glucose and mucin as the sole nitrogen source, contained proteolytic activity against biotin-labelled mucin which was inhibited by pepstatin A. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the culture filtrate revealed two components of 42 and 45 kDa, with pIs of 4.1 and 5.3, respectively. A zymogram showed that mucin was degraded only by the 42-kDa component, which was also recognized by immunoblotting with an anti-secretory aspartyl proteinase (anti-Sap) 2p monoclonal antibody. The N-terminal sequence of the first 20 amino acids matched that reported for Sap2p. These results demonstrate that Sap2p is responsible for proteolysis of mucin by C. albicans in vitro and may be involved as a virulence factor in the breakdown of mucus and penetration of the mucin barrier by C. albicans. PMID:8890200

  6. Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas

    PubMed Central

    Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren II, George

    2017-01-01

    Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas. PMID:28246486

  7. Dynamic force spectroscopy of parallel individual mucin1-antibody bonds

    SciTech Connect

    Sulchek, T A; Friddle, R W; Langry, K; Lau, E; Albrecht, H; Ratto, T; DeNardo, S; Colvin, M E; Noy, A

    2005-05-02

    We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different number of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for mono-, bi-, and tri-valent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for mono and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.

  8. Genome-wide significant risk associations for mucinous ovarian carcinoma

    PubMed Central

    Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  9. L-carbocisteine reduces neutrophil elastase-induced mucin production.

    PubMed

    Yasuo, Masanori; Fujimoto, Keisaku; Imamura, Hitomi; Ushiki, Atsuhito; Kanda, Shintaro; Tsushima, Kenji; Kubo, Hiroshi; Yamaya, Mutsuo; Kubo, Keishi

    2009-06-30

    Human neutrophil elastase (HNE) exists in high concentrations in airway secretions and produces mucus hypersecretion in patients with chronic obstructive pulmonary disease (COPD). L-carbocisteine improves the quality of life and reduces exacerbation in COPD patients. However the precise mechanism is uncertain. We examined the effects of L-carbocisteine on HNE-induced mucus hypersecretion and on the production of reactive oxygen species (ROS) which is associated with mucin production induced by HNE. NCI-H292, a human lung mucoepidermoid carcinoma cell line, was treated with or without HNE and L-carbocisteine. MUC5AC mRNA expression and ROS production in the cells, and MUC5AC protein concentration in supernatants were measured. HNE increased MUC5AC mRNA expression and MUC5AC protein concentration in supernatants in the cells. L-carbocisteine reduces HNE-induced mRNA expression and protein secretion of MUC5AC. L-carbocisteine also reduced ROS production in the cells induced by HNE. Reduction of HNE-induced mucus secretion by L-carbocisteine in the pulmonary epithelial cells may partly relate to the reduction of ROS.

  10. Mucin-Type O-Glycosylation in Invertebrates.

    PubMed

    Staudacher, Erika

    2015-06-09

    O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood. However, the regulation of the processes and the molecular aspects of defects, especially in correlation with cancer or developmental abnormalities, are still under investigation. The knowledge of the correlating invertebrate systems and evolutionary aspects of these highly conserved biosynthetic events may help improve the understanding of the regulatory factors of this pathway. Invertebrates display a broad spectrum of glycosylation varieties, providing an enormous potential for glycan modifications which may be used for the design of new pharmaceutically active substances. Here, overviews of the present knowledge of invertebrate mucin-type O-glycan structures and the currently identified enzymes responsible for the biosynthesis of these oligosaccharides are presented, and the few data dealing with functional aspects of O-glycans are summarised.

  11. Conjunctival mucin deficiency in complete androgen insensitivity syndrome (CAIS).

    PubMed

    Mantelli, Flavio; Moretti, Costanzo; Micera, Alessandra; Bonini, Stefano

    2007-06-01

    Sex steroid hormones are essential for a healthy ocular surface and the androgen receptor impairment found in patients with complete androgen insensitivity syndrome (CAIS) has been described to cause meibomian gland dysfunction and functional dry eye for lipid tear film layer instability. However, it has not been reported if the mucous layer is also affected. A 37-year-old CAIS patient with persistent symptoms of dry eye underwent ophthalmological examination and was evaluated for qualitative and quantitative tear function tests and conjunctival cytology. Samples obtained from the conjunctival epithelium were stained for histology and immunohistochemistry and compared with three age-matched female controls. Western blot and relative real-time RT-PCR for MUC1 and MUC5AC were also performed on these samples. Immunohistochemistry, Western blot and relative real-time RT-PCR showed a decrease in the expression of MUC1 and MUC5AC in CAIS. Changes in the tear film mucous layer were accompanied by a reduction in the tear film break up time test. This is the first report describing mucous layer alteration associated with androgen receptor impairment. Decreased mucin levels contribute in explaining the tear film instability in CAIS and should be considered an additional cause of dry eye in sex steroid hormone pathology.

  12. Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes?

    PubMed Central

    Guyonnet Duperat, V; Audie, J P; Debailleul, V; Laine, A; Buisine, M P; Galiegue-Zouitina, S; Pigny, P; Degand, P; Aubert, J P; Porchet, N

    1995-01-01

    To date five human mucin cDNAs (MUC2, 5A, 5B, 5C and 6) mapped to 11p15.3-15.5, so it appears that this chromosome region might contain several distinct gene loci for mucins. Three of these cDNAs, MUC5A, B and C, were cloned in our laboratory and previously published. A common number, 5, was recommended by the Human Gene Mapping Nomenclature Committee to designate them because of their common provenance from human tracheobronchial mucosa. In order to define whether they are products of the same gene locus or distinct loci, we describe in this paper physical mapping of these cDNAs using the strategy of analysis of CpG islands by pulse-field gel electrophoresis. The data suggest that MUC5A and MUC5C are part of the same gene (called MUC5AC) which is distinct from MUC5B. In the second part of this work, complete sequences of the inserts corresponding to previously described (JER47, JER58) and novel (JER62, JUL32, MAR2, MAR10 and MAR11) cDNAs of the so-called MUC5AC gene are presented and analysed. The data show that in this mucin gene, the tandem repeat domain is interrupted several times with a subdomain encoding a 130 amino acid cysteine-rich peptide in which the TR3A and TR3B peptides previously isolated by Rose et al. [Rose, Kaufman and Martin (1989) J. Biol. Chem., 264, 8193-8199] from airway mucins are found. A consensus peptide sequence for these subdomains involving invariant positions of most of the cysteines is proposed. The consensus nucleotide sequence of this subdomain is also found in the MUC2 gene and in the MUC5B gene, two other mucin genes mapped to 11p15. The functional significance for secreted mucins of these cysteine-rich subdomains and the modular organization of mucin peptides are discussed. Images Figure 3 Figure 4 Figure 5 Figure 8 PMID:7826332

  13. Intestinal mucin distribution in the germ-free rat and in the heteroxenic rat harbouring a human bacterial flora: effect of inulin in the diet.

    PubMed

    Fontaine, N; Meslin, J C; Lory, S; Andrieux, C

    1996-06-01

    A colorimetric method was used on water-soluble mucin extracted from mucosal scrapings and contents of the caecum and the colon of five germ-free (GF) rats and five heteroxenic (HE) rats harbouring a human flora (GF rats associated with a human flora). These rats were fed on a diet containing either 100 g sucrose/kg or 100 g inulin/kg. Histological stains, periodic acid-Schiff, alcian blue pH 2.5 and alcian blue pH 0.5 were used to discriminate between neutral, acidic and acidic sulphated mucins respectively. Spectrocolorimetric assays led to a calculated absorbance value for 1 mg of the initial mucin extract. Each mucin type was compared between treatments. The caecal contents of GF rats contained more acidic mucin than sulphomucin, which was present in the same proportion as neutral mucin. Their colonic contents contained more acidic mucins than sulphomucin, which in turn was more abundant than neutral mucin. Their caecal mucosa mucin distribution differed from that of the contents: very little acidic mucin was present and neutral and sulphomucin proportions were of the same order of magnitude. Inulin increased the amount of neutral mucin in the caecal contents and of sulphated mucins in the colonic contents and increased the amounts of neutral and acidic mucins in the caecal mucosa. Mucin distribution in the HE rats was very different from that in the GF rats: the caecal contents contained a high proportion of acidic mucins and very little sulphomucin. The same distribution of mucins was observed in the colonic contents. The caecal mucosa contained less acidic mucin and more sulphomucin than the caecal contents. Inulin decreased acidic mucins and increased sulphated mucins in the caecal contents and increased neutral and sulphated mucins in the colonic contents. Inulin increased sulphomucin in the caecal mucosa and decreased acidic mucin in the caecal and colonic mucosas. The very low amount of mucin that was recovered in the colonic mucosa suggests that, in the

  14. [Giant esophageal fibrovascular polyp].

    PubMed

    Palacios, Fernando; Contardo, Carlos; Guevara, Jorge; Vera, Augusto; Aguilar, Luis; Huamán, Manuel; Palomino, Américo; Yabar, Alejandro

    2003-01-01

    Fibrovascular polyps are extremely rare benign neoplasias of the esophagus, which usually originate in the lower cricoid area. They do not produce any discomfort in the patient for a long time, however it may make itself evident by the patient's regurgitation of the polyp, producing asphyxia or, more frequently, dysphagia. The case of a 58 year old male patient is presented herein, with a 9 month record of dysphagia, weight loss and intermittent melena. The barium x-ray showed a distended esophagus, with a tumor running from the upper esophageal sphincter to the cardia. The endoscopy confirmed the presence of a pediculated tumor, implanted in the cervical esophagus. Surgeons suspected the potential malignancy of the tumor and performed a transhiatal esophagectomy. The final pathologic diagnosis was giant fibrovascular esophageal polyp.

  15. Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-03-09

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  16. Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-04-13

    Clear Cell Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Mucinous Adenocarcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  17. Complex N-Glycans Are Essential, but Core 1 and 2 Mucin O-Glycans, O-Fucose Glycans, and NOTCH1 Are Dispensable, for Mammalian Spermatogenesis1

    PubMed Central

    Batista, Frank; Lu, Linchao; Williams, Suzannah A.; Stanley, Pamela

    2012-01-01

    ABSTRACT To identify roles in spermatogenesis for major subclasses of N- and O-glycans and Notch signaling, male mice carrying floxed C1galt1, Pofut1, Notch1 or Mgat1 alleles and a testis-specific Cre recombinase transgene were generated. T-synthase (C1GALT1) transfers Gal to generate core 1 and core 2 mucin O-glycans; POFUT1 transfers O-fucose to particular epidermal growth factor-like repeats and is essential for canonical Notch signaling; and MGAT1 (GlcNAcT-I) transfers GlcNAc to initiate hybrid and complex N-glycan synthesis. Cre recombinase transgenes driven by various promoters were investigated, including Stra8-iCre expressed in spermatogonia, Sycp1-Cre expressed in spermatocytes, Prm1-Cre expressed in spermatids, and AMH-Cre expressed in Sertoli cells. All Cre transgenes deleted floxed alleles, but efficiencies varied widely. Stra8-iCre was the most effective, deleting floxed Notch1 and Mgat1 alleles with 100% efficiency and floxed C1galt1 and Pofut1 alleles with ∼80% efficiency, based on transmission of deleted alleles. Removal of C1galt1, Pofut1, or Notch1 in spermatogonia had no effect on testicular weight, histology, or fertility. However, males in which the synthesis of complex N-glycans was blocked by deletion of Mgat1 in spermatogonia did not produce sperm. Spermatogonia, spermatocytes, and spermatids were generated, but most spermatids formed giant multinucleated cells or symplasts, and apoptosis was increased. Therefore, although core 1 and 2 mucin O-glycans, NOTCH1, POFUT1, O-fucose glycans, and Notch signaling are dispensable, MGAT1 and complex N-glycans are essential for spermatogenesis. PMID:22492969

  18. Giant resonances: Progress, new directions, new challenges

    SciTech Connect

    Bertrand, J.R.; Beene, J.R.

    1989-01-01

    A review of some recent developments in the field of giant multipole resonances is presented. Particular emphasis is placed on directions that the authors feel will be followed in this field during the next several years. In particular, the use of high-energy heavy ions to excite the giant resonances is shown to provide exciting new capabilities for giant resonance studies. Among subjects covered are: Coulomb excitation of giant resonances, photon decay of giant resonances, the recent controversy over the identity of the giant monopole resonance, the most recent value for incompressibility of nuclear matter from analysis of giant monopole data, the isospin character of the 63 A/sup /minus/1/3/ GQR, agreement between (e,e/prime/) and (hadron, hadron/prime/) excitation of the giant quadrupole resonance, prospects for multiphonon giant resonance observation, and isolation of the isovector giant quadrupole resonance. 55 refs., 23 figs., 4 tabs.

  19. "Mucin"-secreting papillary renal cell carcinoma: clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases.

    PubMed

    Pivovarcikova, Kristyna; Peckova, Kvetoslava; Martinek, Petr; Montiel, Delia Perez; Kalusova, Kristyna; Pitra, Tomas; Hora, Milan; Skenderi, Faruk; Ulamec, Monika; Daum, Ondrej; Rotterova, Pavla; Ondic, Ondrej; Dubova, Magdalena; Curik, Romuald; Dunatov, Ana; Svoboda, Tomas; Michal, Michal; Hes, Ondrej

    2016-07-01

    Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by

  20. Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon

    PubMed Central

    Barcelo, A; Claustre, J; Moro, F; Chayvialle, J; Cuber, J; Plaisancie, P

    2000-01-01

    BACKGROUND—Mucins play an important protective role in the colonic mucosa. Luminal factors modulating colonic mucus release have been not fully identified.
AIM—To determine the effect of some dietary compounds on mucus discharge in rat colon.
METHODS—An isolated vascularly perfused rat colon model was used. Mucus secretion was induced by a variety of luminal factors administered as a bolus of 1 ml for 30 minutes in the colonic loop. Mucin release was evaluated using a sandwich enzyme linked immunosorbent assay supported by histological analysis.
RESULTS—The three dietary fibres tested in this study (pectin, gum arabic, and cellulose) did not provoke mucus secretion. Luminal administration of sodium alginate (an algal polysaccharide used as a food additive) or ulvan (a sulphated algal polymer) induced a dose dependent increase in mucin discharge over the concentration range 1-25 mg/l (p<0.05 for 25 mg/l alginate and p<0.05 for 10 and 25 mg/l ulvan). Glucuronic acid and galacturonic acid, which are major constituents of a variety of fibres, produced significant mucin secretion (p<0.05). Hydrogen sulphide and mercaptoacetate, two sulphides produced in the colonic lumen by microbial fermentation of sulphated polysaccharides, did not modify mucin secretion. Among the short chain fatty acids, acetate (5-100 mM) induced a dose dependent release of mucus (p<0.05 for 100 mM acetate). Interestingly, butyrate at a concentration of 5 mM produced colonic mucin secretion (p<0.05), but increasing its concentration to 100 mM provoked a gradual decrease in mucus discharge. Propionate (5-100 mM) did not induce mucin release. Several dietary phenolic compounds (quercetin, epicatechin, resveratrol) did not provoke mucus discharge.
CONCLUSIONS—Two algal polysaccharides (alginate and ulvan), two uronic acids (glucuronic acid and galacturonic acid), and the short chain fatty acids acetate and butyrate induce mucin secretion in rat colon. Taken together, these

  1. Giant Hedge-Hogs: Spikes on Giant Gravitons

    SciTech Connect

    Sadri, D

    2004-01-28

    We consider giant gravitons on the maximally supersymmetric plane-wave background of type IIB string theory. Fixing the light-cone gauge, we work out the low energy effective light-cone Hamiltonian of the three-sphere giant graviton. At first order, this is a U(1) gauge theory on R x S{sup 3}. We place sources in this effective gauge theory. Although non-vanishing net electric charge configurations are disallowed by Gauss' law, electric dipoles can be formed. From the string theory point of view these dipoles can be understood as open strings piercing the three-sphere, generalizing the usual BIons to the giant gravitons, BIGGons. Our results can be used to give a two dimensional (worldsheet) description of giant gravitons, similar to Polchinski's description for the usual D-branes, in agreement with the discussions of hep-th/0204196.

  2. Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13

    PubMed Central

    Bucki, Robert; Namiot, Dorota B.; Namiot, Zbigniew; Savage, Paul B.; Janmey, Paul A.

    2008-01-01

    Objectives Cationic antimicrobial peptides (CAPs) are the effector molecules of innate immunity, similar in potency to classic antibiotics that function in the first-line of defence against infectious agents. The purpose of this study was to investigate the effects of negatively charged mucins on the antibacterial activity of the positively charged cathelicidin LL-37 peptide, its synthetic analogue WLBU2 and the antimicrobial cationic steroid CSA-13. Methods Mucin, DNA, F-actin and hCAP-18/LL-37 in saliva samples were evaluated by microscopy or immunoblotting. Bacterial killing assays and determination of MICs were used to determine bactericidal activity. Binding of rhodamine-B-labelled LL-37 peptide to mucin was fluorimetrically assessed. Results Microscopic evaluation of saliva after addition of rhodamine-B-labelled LL-37 showed localization similar to that observed after the addition of a specific mucin-binding lectin. Immunoblotting confirmed the presence of hCAP-18/LL-37 in saliva samples and LL-37 peptide bound to isolated submaxillary gland mucin-coated plates. Mucin/LL-37 binding was partially prevented by treatment of mucin with neuraminidase, indicating involvement of sialic acid moieties. Decreased LL-37 and WLBU2 antibacterial activity was observed in the presence of mucin or dialysed human saliva, whereas CSA-13 antibacterial activity was significantly resistant to inhibition by mucins. Conclusions This study shows that the antibacterial LL-37 peptide and its synthetic analogue WLBU2 are inhibited by salivary mucin and that the cationic steroid CSA-13 retains most of its function in the presence of an equal amount of mucin or saliva. PMID:18456648

  3. A giant Ordovician anomalocaridid.

    PubMed

    Van Roy, Peter; Briggs, Derek E G

    2011-05-26

    Anomalocaridids, giant lightly sclerotized invertebrate predators, occur in a number of exceptionally preserved early and middle Cambrian (542-501 million years ago) biotas and have come to symbolize the unfamiliar morphologies displayed by stem organisms in faunas of the Burgess Shale type. They are characterized by a pair of anterior, segmented appendages, a circlet of plates around the mouth, and an elongate segmented trunk lacking true tergites with a pair of flexible lateral lobes per segment. Disarticulated body parts, such as the anterior appendages and oral circlet, had been assigned to a range of taxonomic groups--but the discovery of complete specimens from the middle Cambrian Burgess Shale showed that these disparate elements all belong to a single kind of animal. Phylogenetic analyses support a position of anomalocaridids in the arthropod stem, as a sister group to the euarthropods. The anomalocaridids were the largest animals in Cambrian communities. The youngest unequivocal examples occur in the middle Cambrian Marjum Formation of Utah but an arthropod retaining some anomalocaridid characteristics is present in the Devonian of Germany. Here we report the post-Cambrian occurrence of anomalocaridids, from the Early Ordovician (488-472 million years ago) Fezouata Biota in southeastern Morocco, including specimens larger than any in Cambrian biotas. These giant animals were an important element of some marine communities for about 30 million years longer than previously realized. The Moroccan specimens confirm the presence of a dorsal array of flexible blades attached to a transverse rachis on the trunk segments; these blades probably functioned as gills.

  4. Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.

    PubMed

    Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B; Tinder, Teresa L; Mason, Hugh S; Walmsley, Amanda M; Gendler, Sandra J; Mukherjee, Pinku

    2010-12-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

  5. Analysis of a Cholera Toxin B Subunit (CTB) and Human Mucin 1 (MUC1) Conjugate Protein in a MUC1 Tolerant Mouse Model

    PubMed Central

    Pinkhasov, Julia; Alvarez, M. Lucrecia; Pathangey, Latha B.; Tinder, Teresa L.; Mason, Hugh S.; Walmsley, Amanda M.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1 tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12), did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. PMID:20824430

  6. Imaging patterns of intraductal papillary mucinous neoplasms of the pancreas: an illustrated discussion of the International Consensus Guidelines for the Management of IPMN.

    PubMed

    Campbell, Naomi M; Katz, Seth S; Escalon, Joanna G; Do, Richard K

    2015-03-01

    Intraductal papillary mucinous neoplasms (IPMN) are being diagnosed with increasing frequency, necessitating an algorithm to help stratify patients into low- and high-risk groups, for follow-up versus more invasive evaluation. New evidence concerning their natural history and overall risk of malignancy has emerged since the 2006 International Association of Pancreatology consensus guidelines, prompting an update in 2012, that distinguishes radiologic 'worrisome features' from 'high-risk stigmata'. The aim of this article is to illustrate, with case examples, the variable imaging patterns of IPMN and how their radiologic features, such as cyst size and mural nodules, are interpreted in the context of the new 2012 guidelines. The 2012 and 2006 guidelines will be compared and discussed with reference to additional studies that have since been published. Despite these guidelines, lingering uncertainty remains about the natural history of IPMN, a source of unease to both radiologists and referring clinicians alike, mandating further refinement of clinical and radiologic parameters predictive of malignancy. Emerging data regarding the risk of extrapancreatic malignancy, as well as synchronous or metachronous pancreatic ductal adenocarcinoma remote in location from a branch duct IPMN are also reviewed. With the expanding research and evolving understanding of this clinicopathologic entity across the globe, radiologists will continue to play an important role in the management of patients with IPMN.

  7. Intraductal papillary mucinous neoplasia (IPMN). Highlights from the "2010 ASCO Gastrointestinal Cancers Symposium". Orlando, FL, USA. January 22-24, 2010.

    PubMed

    Bussom, Scott; Saif, Muhammad Wasif

    2010-03-05

    The diagnosis and treatment of intraductal papillary mucinous tumors (IPMN) of the pancreas has evolved over the last decade. IPMN is a disease of the ductal epithelium and represent a spectrum of disease, ranging from benign to malignant lesions, making the early detection and characterization of these lesions important. As with villous adenomas of the colon, not all IPMNs will develop into adenocarcinoma. Definitive management is surgical resection for appropriate candidates, as benign lesions harbor malignant potential. Growing controversy revolves around issues of natural history, management of small-branch-duct lesions, ability to predict malignancy and/or progression, and surveillance strategies. Given these controversies, novel methods are needed to help in detecting and classifying IPMNs' malignant potential so that appropriate treatment can be administered. The authors review abstracts from the 2010 ASCO Gastrointestinal Cancers Symposium held in January 2010, including biomarkers helping to classify IPMNs: IL-8 and IL-1beta from IPMN cyst aspirates (Abstract #133), and Foxp3/CD4/CD25 cells (Abstract #148) in peripheral blood. Future studies will hopefully provide insight into the many unanswered questions.

  8. MZF-1 and DbpA interact with DNase I hypersensitive sites that correlate with expression of the human MUC1 mucin gene

    SciTech Connect

    Shiraga, Toshiyuki; Winpenny, John P.; Carter, Emma J.; McCarthy, Victoria A.; Hollingsworth, Michael A.; Harris, Ann . E-mail: ann.harris@paediatrics.ox.ac.uk

    2005-08-01

    The MUC1 mucin is a large membrane-tethered glycoprotein that shows differential expression in many adenocarcinomas, where it contributes to their invasive and metastatic properties. We previously identified DNase I hypersensitive sites at -750 and -250 bp in the human MUC1 gene promoter and showed concordance between the -250 site and MUC1 mRNA levels in vivo. Transient expression assays using promoter constructs, in which the core DHS was deleted, to drive reporter gene expression revealed in vivo evidence for their activity. DNase I footprinting using nuclear extracts from HPAF human pancreatic carcinoma cells and MCF7 breast carcinoma cells identified three protein-binding elements in these regions (-250FP1, FP2 and -750FP). Electrophoretic mobility shift assays detected several complexes between HPAF nuclear proteins and labeled FP DNA probes. Southwestern blots and UV cross-linking experiments identified myeloid zinc finger-1 (MZF-1) as a candidate transcription factor among proteins binding to the -250FP1 and FP2 sequences. Another candidate that was identified by screening an HPAF cDNA expression library with the -250FP1 probe is DNA binding protein A (DbpA). Exogenous DbpA expression in COS-7 cells was accompanied by upregulation of MUC1 promoter activity via the -250 DHS, suggesting that DbpA binding to the -250 DHS can influence human MUC1 gene expression.

  9. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

    PubMed Central

    Crost, Emmanuelle H.; Tailford, Louise E.; Le Gall, Gwenaelle; Fons, Michel; Henrissat, Bernard; Juge, Nathalie

    2013-01-01

    Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease. PMID:24204617

  10. Immunochemical characterization of mucins. Polypeptide (M1) and polysaccharide (A and Leb) antigens.

    PubMed Central

    Bara, J; Gautier, R; Le Pendu, J; Oriol, R

    1988-01-01

    Seven monoclonal antibodies (MAbs) reacting with high-molecular-mass components (greater than 20,000 kDa) isolated from an ovarian mucinous cyst of an A Le(a-b+) patient are described. By the use of immunoradiometric methods, these MAbs characterized seven different epitopes associated with components having a density of 1.45 g/ml by CsCl-density-gradient ultracentrifugation, like mucins. Two MAbs reacted with A and Lewis blood-group antigens respectively (polysaccharide epitopes). The five other MAbs characterized five M1 epitopes (called a, b, c, d and e), mainly associated with components of more than 20,000 kDa and 2000 kDa. They were completely destroyed by papain and 2-mercaptoethanol treatment (polypeptide epitopes). Moreover, timed trypsin digestion of native mucin resulted in a progressive loss of M1 activity and degraded these mucins into smaller M1-positive fragments. The a and c epitopes were partially degraded from relatively high-molecular-mass fragments (2000 kDa to 500 kDa) into a 100 kDa fragment. The b and d epitopes were completely degraded into smaller fragments ranging from 100 kDa to 40 kDa. The e epitope was completely destroyed by trypsin. These different pathways of M1 antigen degradation suggest the occurrence of different epitopes located in separate regions of the mucin molecules. Images Fig. 5. Fig. 7. PMID:2460087

  11. Immunological characterization of deglycosylated human and swine trachea and Cowper's gland mucin glycoproteins.

    PubMed

    Sangadala, S; Brewer, J M; Mendicino, J

    1991-04-01

    Antibodies were raised in rabbits against purified swine and human trachea and Cowper's gland mucin glycoproteins and their deglycosylated polypeptide chains. Three monospecific antibody fractions that recognize the carbohydrate, the deglycosylated or unglycosylated regions of the polypeptide chains in these glycoproteins, were isolated by immunoaffinity chromatography. The human and swine trachea mucin glycoproteins showed extensive immunological homology in both their carbohydrate and polypeptide chains. The carbohydrate chains and unglycosylated region of the polypeptide chain in Cowper's gland mucin glycoprotein showed little or no cross-reaction with comparable regions in respiratory mucin glycoproteins. However, the polypeptide chains in the deglycosylated regions of all three mucin glycoproteins showed extensive homology. Five bands with molecular masses ranging from 40 to 46 kDa that differed by a constant molecular mass of approximately 1.5 kDa were detected in hydrolysates of all of the polypeptide chains after treatment with S. aureus V8 protease. Monospecific antibodies to the deglycosylated region of these chains reacted with the peptides, whereas those directed against the unglycosylated region did not. The results suggest that these chains contain tandem repeating sequences of amino acids.

  12. A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei.

    PubMed

    Pillai, Krishna; Akhter, Javed; Chua, Terence C; Morris, David L

    2014-01-15

    Although numerous clinical attempts have been made to disintegrate mucin secreted by pseudomyxoma peritonei (PMP), none are clinically recommended. Through examination of the pharmacologic characteristics of two novel agents, we titrated an optimized combination of bromelain and N-acetyl cysteine (NAC) that demonstrates in vitro and in vivo efficacy in the dissolution of mucinous ascites from PMP. In the in vitro experiments, 1 g of mucin was incubated in varying concentrations of bromelain (0-400 µg/ml) and NAC (0-5%) individually followed by a combination before arriving at a therapeutic combination dose of 300 µg/ml bromelain+4% NAC. This established an effective dose of bromelain 300 µg/ml+4% NAC at pH 7.0, when tested in a rat model implanted with 3 g of mucin intraperitoneally (IP). IP administration of the drug in a rat model of PMP was shown to result in mucin disintegration within 72 hr with no toxicity observed.

  13. Metastatic chordoma of the breast: an extremely rare lesion mimicking mucinous cancer.

    PubMed

    Tot, Tibor

    2006-10-01

    Metastases in the breast are rare, with metastatic chordoma being one of the rarest. To our knowledge, only one such case has previously been published in the literature. We report a case of a 74-year-old woman who presented with a palpable lump in her right breast. The lump was mammographically suggestive of mucinous breast cancer because it was a solitary, small, circular, and moderately dense lesion yielding abundant mucoid aspirate. The tumor resembled mucinous carcinoma upon histologic and immunohistochemical examination: it had a mucinous stroma, and the tumor cells strongly expressed epithelial markers. However, the patient had previously undergone surgery for a recurrent sacral chordoma. In addition to the clinical history, the presence of typical physaliferous cells expressing neither estrogen receptors nor cytokeratin 7, but staining positively for S-100 protein, allowed the proper diagnosis. Although extremely rare, metastatic chordoma may represent a challenge in the differential diagnosis of breast lesions. Discriminating metastases of mucin-producing tumors in the breast from primary mucinous carcinomas is important with regard to the striking difference in prognosis of these lesions.

  14. Phytic acid increases mucin and endogenous amino acid losses from the gastrointestinal tract of chickens.

    PubMed

    Onyango, Edward M; Asem, Elikplimi K; Adeola, Olayiwola

    2009-03-01

    The influence of the form of phytic acid on the regulation of mucin and endogenous losses of amino acids, nitrogen and energy in chickens was investigated. Forty-eight 10-week-old male broilers were grouped by weight into eight blocks of six cages with one bird per cage. Birds received by intubation six dextrose-based combinations of phytic acid and phytase arranged in a 3 x 2 factorial consisting of phytic acid form (no phytic acid, 1.0 g free phytic acid or 1.3 g magnesium-potassium phytate) and phytase (0 or 1000 units). Each bird received the assigned combination added to 25 g dextrose at each of the two feedings on the first day of experimentation. All excreta were collected continuously for 54 h following feeding and frozen until analysed. Frozen excreta were thawed, pooled for each bird, lyophilised, ground, and analysed for DM, energy, nitrogen, amino acids, mucin, and sialic and uric acids. Chickens fed either magnesium-potassium phytate or free phytic acid showed increased (P < 0.05) loss of crude mucin and sialic acid. The amount of crude mucin lost was significantly greater (P < 0.05) with magnesium-potassium phytate than with free phytic acid treatment. Both phytic acid treatments also increased (P < 0.05) endogenous loss of threonine, proline and serine. In conclusion, the form of phytic acid fed to chickens affects the extent of mucin and endogenous amino acid losses from the gastrointestinal tract.

  15. Early colonic dysplasia: comparison of differential mucin staining and tritiated thymidine labeling

    SciTech Connect

    Chabot, J.A.; Colacchio, T.A.

    1985-01-01

    Controversy has arisen regarding the interpretation and significance of histochemical changes in the mucin produced by the globlet cells in colonic mucosa. The shift from sulfomucin to sialomucin, which is readily identified utilizing high iron diamine-alcian blue staining techniques, has been alternately interpreted as a specific, early dysplastic and premalignant change or a nonspecific generalized response to trauma and inflammation, among others. An attempt to clarify this issue was made by comparing mucin changes identified by high iron diamine-alcian blue staining techniques with increases in DNA synthetic activity identified utilizing autoradiographic analysis of tritiated thymidine uptake. Male Holtzman rats were treated with 15 weekly subcutaneous injections of dimethylhydrazine (30 mg/kg per week) (10 rats) or placebo (10 rats). The colons were prepared and fixed, sequential sections were stained with hematoxylin-eosin or high iron diamine-alcian blue, autoradiography was performed. Analyses of labeling index showed no difference in normal background crypts between the control and treatment groups nor in crypts adjacent to those displaying abnormal mucin staining. Crypts with abnormal mucin production (sialomucin dominant) had significantly higher labeling indexes when compared with those of control animals (p less than 0.005). These findings indicate that the shifts in mucin production identified with high iron diamine-alcian blue staining represent crypts with increased and abnormally distributed mitotic activity that is an early dysplastic response to the carcinogenic stimulus.

  16. Probing the interaction of nanoparticles with mucin for drug delivery applications using dynamic light scattering.

    PubMed

    Griffiths, Peter Charles; Cattoz, Beatrice; Ibrahim, Mervat Shafik; Anuonye, Josephine Chibuzor

    2015-11-01

    Drug delivery via the eye, nose, gastrointestinal tract and lung is of great interest as they represent patient-compliant and facile methods to administer drugs. However, for a drug to reach the systemic circulation it must penetrate the "mucus barrier". An understanding of the characteristics of the mucus barrier is therefore important in the design of mucus penetrating drug delivery vehicles e.g. nanoparticles. Here, a range of nanoparticles - silica, aluminium coated silica, poly (lactic-co-glycolic acid) (PLGA) and PEGylated PLGA - each with known but different physicochemical characteristics were examined in the presence of mucin to identify those characteristics that engender nanoparticle/mucin interactions and thus, to define "design rules" for mucus penetrating (nano)particles (MPP), at least in terms of the surface characteristics of charge and hydrophilicity. Dynamic light scattering (DLS) and rheology have been used to assess the interaction between such nanoparticles and mucin. It was found that negatively charged and hydrophilic nanoparticles do not exhibit an interaction with mucin whereas positively charged and hydrophobic nanoparticles show a strong interaction. Surface grafted poly (ethylene glycol) (PEG) chains significantly reduced this interaction. This study clearly demonstrates that the established colloid science techniques of DLS and rheology are very powerful screening tools to probe nanoparticle/mucin interactions.

  17. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  18. Effectiveness of contrast-enhanced endoscopic ultrasound for detecting mural nodules in intraductal papillary mucinous neoplasm of the pancreas and for making therapeutic decisions

    PubMed Central

    Fujita, Mitsuru; Itoi, Takao; Ikeuchi, Nobuhito; Sofuni, Atsushi; Tsuchiya, Takayoshi; Ishii, Kentaro; Kamada, Kentaro; Umeda, Junko; Tanaka, Reina; Tonozuka, Ryosuke; Honjo, Mitsuyoshi; Mukai, Shuntaro; Moriyasu, Fuminori

    2016-01-01

    Background and Objectives: There have been few studies to date evaluating the effectiveness of contrast-enhanced endoscopic ultrasound (CE-EUS) for detecting mural nodules in patients with branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas. We aim to evaluate the effectiveness of CE-EUS for detecting mural nodules in BD-IPMN. Patients and Methods: Of the 427 BD-IPMN patients, 21 patients (4.9%) in whom the presence of mural nodules was suggested by CE computed tomography (CT) or magnetic resonance imaging (MRI), or in whom the presence of nodule-like lesions as shown by fundamental EUS, were examined by CE-EUS. Results: The mean diameter of cystic lesions was 29.8 ± 12.8 mm. The mean diameter of mural nodules was 9.5 ± 5.7 mm. BD-IPMN was detected in the pancreatic head in 16 cases, pancreatic body in 2 cases, and pancreatic tail in 3 cases. The mean follow-up period was 17.2 ± 11.9 months. The detection rates of mural nodule-like lesions in BD-IPMN patients on CT, MRI, and fundamental EUS were 36.8%, 63.2%, and 100%, respectively. The detection rates of true mural nodules in BD-IPMN patients on CT, MRI, and fundamental EUS were 85.7%, 71.4%, and 100%, respectively. The echo levels of mural nodule-like lesions on fundamental EUS were hyperechoic in 6 patients, isoechoic in 9 patients, and hypoechoic in 6 patients. The final diagnosis was mucus lumps in 14 patients and mural nodules in 7 patients. The contrast patterns observed were avascular, isovascular, and hypervascular in 14, 3, and 4 patients, respectively. No patients showed a hypovascular pattern. Fourteen patients showing an avascular pattern were diagnosed as having mucus lumps, and they were able to avoid surgical resection. Of the 7 patients who were diagnosed as having mural nodules, 5 underwent surgical resection. The pathological findings were adenocarcinoma in 2 patients and adenoma in 3 patients. Of the 3 adenoma patients, fundamental EUS demonstrated a hypoechoic

  19. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  20. Eccrine adenocarcinoma of the footpads in 2 cats.

    PubMed Central

    Fuentealba, I C; Illanes, O G; Haines, D M

    2000-01-01

    Adenocarcinoma of sweat glands of the footpads was diagnosed in 2 cats. Clinical signs included lameness and swelling of multiple digits. Pulmonary metastasis was detected in one case. Diagnosis was based on histopathological and immunohistochemical findings. Eccrine adenocarcinoma should be included in the differential diagnosis of footpads lesions in aged cats. Images Figure 1. Figure 2. PMID:10816835

  1. Pharma giants swap research programs.

    PubMed

    2014-07-01

    Pharmaceutical giants Novartis and GlaxoSmithKline (GSK) agreed in late April to swap some assets, with Novartis handing off its vaccine business to GSK and getting most of the British company's cancer portfolio in return.

  2. Theories of Giant Planet Formation

    NASA Technical Reports Server (NTRS)

    Lissauer, Jack J.; Young, Richard E. (Technical Monitor)

    1998-01-01

    An overview of current theories of planetary formation, with emphasis on giant planets, is presented. The most detailed models are based upon observations of our own Solar System and of young stars and their environments. While these models predict that rocky planets should form around most single stars, the frequency of formation of gas giant planets is more difficult to predict theoretically. Terrestrial planets are believed to grow via pairwise accretion until the spacing of planetary orbits becomes large enough that the configuration is stable for the age of the system. Giant planets begin their growth as do terrestrial planets, but they become massive enough that they are able to accumulate substantial amounts of gas before the protoplanetary disk dissipates. Most models for extrasolar giant planets suggest that they formed as did Jupiter and Saturn (in nearly circular orbits, far enough from the star that ice could), and subsequently migrated to their current positions, although some models suggest in situ formation.

  3. Lichens On Galapagos Giant Tortoises.

    PubMed

    Hendrickson, J R; Weber, W A

    1964-06-19

    The association of Physcia picta with the giant Galdpagos tortoise is believed to be the first reported occurrence of lichens on land animals. The habitat is restricted to specific sites on the carapace of male tortoises.

  4. Landscape of the lost giants

    NASA Astrophysics Data System (ADS)

    2013-09-01

    The Pleistocene megafauna extinction erased a group of remarkable animals. Whether humans had a prominent role in the extinction remains controversial, but it is emerging that the disappearance of the giants has markedly affected the environment.

  5. Atmospheres of Extrasolar Giant Planets

    NASA Technical Reports Server (NTRS)

    Marley, Mark

    2006-01-01

    The next decade will almost certainly see the direct imaging of extrasolar giant planets around nearby stars. Unlike purely radial velocity detections, direct imaging will open the door to characterizing the atmosphere and interiors of extrasola planets and ultimately provide clues on their formation and evolution through time. This process has already begun for the transiting planets, placing new constraints on their atmospheric structure, composition, and evolution. Indeed the key to understanding giant planet detectability, interpreting spectra, and constraining effective temperature and hence evolution-is the atmosphere. I will review the universe of extrasolar giant planet models, focusing on what we have already learned from modeling and what we will likely be able to learn from the first generation of direct detection data. In addition to these theoretical considerations, I will review the observations and interpretation of the - transiting hot Jupiters. These objects provide a test of our ability to model exotic atmospheres and challenge our current understanding of giant planet evolution.

  6. Mucin1 expression in focal epidermal dysplasia of actinic keratosis

    PubMed Central

    Carrillo, Luz Marina; Rojas, Héctor; Ramírez, Richard; Reyes, Oscar; Suárez, Ambar; Ortega, Fabiana

    2015-01-01

    Background Actinic keratoses (AKs) are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) in situ and invasive SCC. However, its progression to SCC is still matter of debate. A transmembrane glycoprotein that contributes to the progression of certain premalignant and malignant lesions is mucin1 (MUC1). Nevertheless, their functions in the skin lesions are not yet fully clear. Therefore, the aim of this study is to ascertain whether MUC1 is present in the focal epidermal dysplasia of AK. Methods Fourteen skin biopsies from patients diagnosed with AK were selected. They were classified according to the degree of dysplasia in keratinocyte intraepidermal neoplasia (KIN) I, KIN II, and KIN III. In five biopsies the three degrees were present, in two biopsies both KIN I and KIN II, in four biopsies only KIN I, and in three biopsies only KIN III. The presence of MUC1 was assessed by immunofluorescence staining using confocal laser scanning microscopy. Results Immunostaining revealed that MUC1 was present over the entire cell surface of only a few atypical basal keratinocytes confined to the lower third of the epidermis (KIN I). While in KIN II where atypical keratinocytes occupy the lower two thirds, MUC1 was localized at the apical surface of some atypical keratinocytes and over the entire cell surface of some of them. Interestingly, in KIN III where the atypical keratinocytes extend throughout the full thickness, MUC1 was localized at the apical surface and over the entire cell surface of many of these cells. Conversely, MUC1 expression was not detected in the epidermis of normal skin. Conclusions Our findings suggest that the expression of MUC1 in AK would be induced by alteration of keratinocyte stratification and differentiation and associated to the degree of dysplasia rather than the thickness of the epidermis. PMID:26605291

  7. Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

    ClinicalTrials.gov

    2016-11-07

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  8. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  9. Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

    ClinicalTrials.gov

    2017-01-25

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  10. Irinotecan and Alisertib in Treating Patients With Advanced Solid Tumors or Colorectal Cancer

    ClinicalTrials.gov

    2016-12-20

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  11. Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-05-15

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  12. Mining the “glycocode”—exploring the spatial distribution of glycans in gastrointestinal mucin using force spectroscopy

    PubMed Central

    Gunning, A. Patrick; Kirby, Andrew R.; Fuell, Christine; Pin, Carmen; Tailford, Louise E.; Juge, Nathalie

    2013-01-01

    Mucins are the main components of the gastrointestinal mucus layer. Mucin glycosylation is critical to most intermolecular and intercellular interactions. However, due to the highly complex and heterogeneous mucin glycan structures, the encoded biological information remains largely encrypted. Here we have developed a methodology based on force spectroscopy to identify biologically accessible glycoepitopes in purified porcine gastric mucin (pPGM) and purified porcine jejunal mucin (pPJM). The binding specificity of lectins Ricinus communis agglutinin I (RCA), peanut (Arachis hypogaea) agglutinin (PNA), Maackia amurensis lectin II (MALII), and Ulex europaeus agglutinin I (UEA) was utilized in force spectroscopy measurements to quantify the affinity and spatial distribution of their cognate sugars at the molecular scale. Binding energy of 4, 1.6, and 26 aJ was determined on pPGM for RCA, PNA, and UEA. Binding was abolished by competition with free ligands, demonstrating the validity of the affinity data. The distributions of the nearest binding site separations estimated the number of binding sites in a 200-nm mucin segment to be 4 for RCA, PNA, and UEA, and 1.8 for MALII. Binding site separations were affected by partial defucosylation of pPGM. Furthermore, we showed that this new approach can resolve differences between gastric and jejunum mucins.—Gunning, A. P., Kirby, A. R., Fuell, C., Pin, C., Tailford L. E., Juge, N. Mining the “glycocode”—exploring the spatial distribution of glycans in gastrointestinal mucin using force spectroscopy. PMID:23493619

  13. Bacillus cereus NVH 0500/00 Can Adhere to Mucin but Cannot Produce Enterotoxins during Gastrointestinal Simulation

    PubMed Central

    Tsilia, Varvara; Kerckhof, Frederiek-Maarten; Heyndrickx, Marc

    2015-01-01

    Adhesion to the intestinal epithelium could constitute an essential mechanism of Bacillus cereus pathogenesis. However, the enterocytes are protected by mucus, a secretion composed mainly of mucin glycoproteins. These may serve as nutrients and sites of adhesion for intestinal bacteria. In this study, the food poisoning bacterium B. cereus NVH 0500/00 was exposed in vitro to gastrointestinal hurdles prior to evaluation of its attachment to mucin microcosms and its ability to produce nonhemolytic enterotoxin (Nhe). The persistence of mucin-adherent B. cereus after simulated gut emptying was determined using a mucin adhesion assay. The stability of Nhe toward bile and pancreatin (intestinal components) in the presence of mucin agar was also investigated. B. cereus could grow and simultaneously adhere to mucin during in vitro ileal incubation, despite the adverse effect of prior exposure to a low pH or intestinal components. The final concentration of B. cereus in the simulated lumen at 8 h of incubation was 6.62 ± 0.87 log CFU ml−1. At that point, the percentage of adhesion was approximately 6%. No enterotoxin was detected in the ileum, due to either insufficient bacterial concentrations or Nhe degradation. Nevertheless, mucin appears to retain B. cereus and to supply it to the small intestine after simulated gut emptying. Additionally, mucin may play a role in the protection of enterotoxins from degradation by intestinal components. PMID:26497468

  14. Bacillus cereus NVH 0500/00 Can Adhere to Mucin but Cannot Produce Enterotoxins during Gastrointestinal Simulation.

    PubMed

    Tsilia, Varvara; Kerckhof, Frederiek-Maarten; Rajkovic, Andreja; Heyndrickx, Marc; Van de Wiele, Tom

    2015-10-23

    Adhesion to the intestinal epithelium could constitute an essential mechanism of Bacillus cereus pathogenesis. However, the enterocytes are protected by mucus, a secretion composed mainly of mucin glycoproteins. These may serve as nutrients and sites of adhesion for intestinal bacteria. In this study, the food poisoning bacterium B. cereus NVH 0500/00 was exposed in vitro to gastrointestinal hurdles prior to evaluation of its attachment to mucin microcosms and its ability to produce nonhemolytic enterotoxin (Nhe). The persistence of mucin-adherent B. cereus after simulated gut emptying was determined using a mucin adhesion assay. The stability of Nhe toward bile and pancreatin (intestinal components) in the presence of mucin agar was also investigated. B. cereus could grow and simultaneously adhere to mucin during in vitro ileal incubation, despite the adverse effect of prior exposure to a low pH or intestinal components. The final concentration of B. cereus in the simulated lumen at 8 h of incubation was 6.62 ± 0.87 log CFU ml(-1). At that point, the percentage of adhesion was approximately 6%. No enterotoxin was detected in the ileum, due to either insufficient bacterial concentrations or Nhe degradation. Nevertheless, mucin appears to retain B. cereus and to supply it to the small intestine after simulated gut emptying. Additionally, mucin may play a role in the protection of enterotoxins from degradation by intestinal components.

  15. Chemotherapy-induced mucositis: the role of mucin secretion and regulation, and the enteric nervous system.

    PubMed

    Thorpe, Daniel; Stringer, Andrea; Butler, Ross

    2013-09-01

    Alimentary mucositis is a severe, dose-limiting, toxic side effect of cytotoxic chemotherapy and radiotherapy. Patients with mucositis often have reductions or breaks imposed on cytotoxic therapy, which may lead to reduced survival. Furthermore, there is an increased risk of infection and hospitalization, compounding the cost of treatment. There are currently limited therapeutic options for mucositis, and no effective prevention available. Mucin expression and secretion have been shown to be associated with mucositis. Furthermore, mucins exhibit protective effects on the alimentary tract through reducing mechanical and chemical stress, preventing bacterial overgrowth and penetration, and digestion of the mucosa. Additionally, a number of studies have implicated some key neurotransmitters in both mucositis and mucin secretion, suggesting that the enteric nervous system may also play a key role in the development of mucositis.

  16. Comparative permeability of some acyclovir derivatives through native mucus and crude mucin dispersions.

    PubMed

    Legen; Kristl, A

    2001-08-01

    The permeability of some guanine derivatives (acyclovir [ACV], deoxyacyclovir [DCV], and their N-acetyl congeners) through native porcine mucus and crude porcine mucin dispersions (30% and 50% w/v) was investigated in two-compartment dialysis cells. High correlation between apparent permeability coefficients Papp of tested substances determined in these two models was observed, although the examined compounds permeated faster through the native mucus. It was also established that Papp values decrease with increasing hydrophilicity and molecular mass of the tested substances. Furthermore, the influence of some substances that affect mucus structure (cysteine, N-acetylcysteine [NCY], sodium taurocholate [ST], and sodium chloride) on the permeation rate of the examined compounds through mucus and mucin dispersions was examined. It was shown that the Papp values of guanine derivatives were generally lower after the addition of these substances to the native mucus and mucin dispersions, although the lowering effect was more pronounced in the case of native mucus.

  17. Probing the Mucoadhesive Interactions Between Porcine Gastric Mucin and Some Water-Soluble Polymers.

    PubMed

    Albarkah, Yasser A; Green, Rebecca J; Khutoryanskiy, Vitaliy V

    2015-11-01

    This study investigates the structural features of porcine gastric mucin (PGM) in aqueous dispersions and its interactions with water-soluble polymers (poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(ethylene oxide), and poly(ethylene glycol)) using isothermal titration calorimetry, turbidimetric titration, dynamic light scattering, and transmission electron microscopy. It is established that PAA (450 kDa) and PMAA (100 kDa) exhibit strong specific interactions with PGM causing further aggregation of its particles, while PAA (2 kDa), poly(ethylene oxide) (1 000 kDa), and poly(ethylene glycol) (10 kDa) do not show any detectable effects on mucin. Sonication of mucin dispersions prior to their mixing with PAA (450 kDa) and PMAA (100 kDa) leads to more pronounced intensity of interactions.

  18. Giants in the Local Region

    NASA Astrophysics Data System (ADS)

    Luck, R. Earle; Heiter, Ulrike

    2007-06-01

    We present parameter and abundance data for a sample of 298 nearby giants. The spectroscopic data for this work have a resolution of R~60,000, S/N>150, and spectral coverage from 475 to 685 nm. Overall trends in the Z>10 abundances are dominated by Galactic chemical evolution, while the light-element abundances are influenced by stellar evolution, as well as Galactic evolution. We find several super-Li stars in our sample and confirm that Li abundances in the first giant branch are related to mixing depths. Once astration of lithium on the main sequence along with the overall range of main-sequence lithium abundances are taken into account, the lithium abundances of the giants are not dramatically at odds with the predictions of standard stellar evolution. We find the giants to be carbon-diluted in accord with standard stellar evolution and that the carbon and oxygen abundances determined for the local giants are consistent with those found in local field dwarfs. We find that there is evidence for systematic carbon variations in the red giant clump in the sense that the blue side of the clump is carbon-poor (more diluted) than the red side.

  19. Toxin Synthesis and Mucin Breakdown Are Related to Swarming Phenomenon in Clostridium septicum

    PubMed Central

    Macfarlane, Sandra; Hopkins, Mark J.; Macfarlane, George T.

    2001-01-01

    Clostridium septicum is responsible for several diseases in humans and animals. The bacterium is capable of a simple kind of multicellular behavior known as swarming. In this investigation, environmental and physiologic factors affecting growth and swarm cell formation in C. septicum were studied over a range of dilution rates (D = 0.02 to 0.65 h−1) in glucose-limited, glucose-excess, and mucin-limited chemostats. Cellular differentiation was observed at low specific growth rates, irrespective of the carbon and energy source, showing that swarming occurred in response to nutrient depletion. Differential expression of virulence determinants was detected in swarm cells. Hemolysin was secreted by short motile rods but not swarm cells, whereas in cultures grown with glucose, only swarm cells formed DNase, hyaluronidase, and neuraminidase. However, neuraminidase and, to a lesser degree, hyaluronidase were induced in short motile rods in mucin-limited cultures. Both swarm cells and short rods were cytotoxic to Vero cells. Mucin was chemotaxic to C. septicum, and large amounts of mucin-degrading enzymes (β-galactosidase, N-acetyl β-glucosaminidase, glycosulfatase, and neuraminidase) were produced. Synthesis of these enzymes was catabolite regulated. In chemostat experiments, glycosulfatase secretion occurred only in swarm cells at low dilution rates in mucin-limited cultures. Determinations of oligosaccharide utilization demonstrated that N-acetylglucosamine, galactose, and N-acetylgalactosamine were the main carbon sources for C. septicum in mucin. Neuraminic acid was not assimilated, showing that neuraminidase does not have a direct nutritional function in this pathogen. PMID:11160009

  20. Vanadium pentoxide (V2O5) induced mucin production by airway epithelium

    PubMed Central

    Yu, Dongfang; Walters, Dianne M.; Zhu, Lingxiang; Lee, Pak-Kei

    2011-01-01

    Exposure to environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as chronic obstructive pulmonary disease and asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them, vanadium has been suggested to play an important role in PM-induced mucin production. Vanadium pentoxide (V2O5) is the most common commercial source of vanadium, and it has been associated with occupational chronic bronchitis and asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V2O5. Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V2O5-induced mucin production. Most interestingly, the reactive oxygen species and the classical mucin-inducing epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V2O5-induced mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V2O5-associated occupational diseases but also advance our understanding on the EGFR-independent mucin production in other chronic airway diseases. PMID:21531775

  1. Cervical mucins carry alpha(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis.

    PubMed

    Domino, Steven E; Hurd, Elizabeth A; Thomsson, Kristina A; Karnak, David M; Holmén Larsson, Jessica M; Thomsson, Elisabeth; Bäckström, Malin; Hansson, Gunnar C

    2009-12-01

    Cervical mucins are glycosylated proteins that form a protective cervical mucus. To understand the role of mucin glycans in Candida albicans infection, oligosaccharides from mouse cervical mucins were analyzed by liquid chromatography-mass spectrometry. Cervical mucins carry multiple alpha(1-2)fucosylated glycans, but alpha(1,2)fucosyltransferase Fut2-null mice are devoid of these epitopes. Epithelial cells in vaginal lavages from Fut2-null mice lacked Ulex europaeus agglutinin-1 (UEA-I) staining for alpha(1-2)fucosylated glycans. Hysterectomy to remove cervical mucus eliminated UEA-I and acid mucin staining in vaginal epithelial cells from wild type mice indicating the cervix as the source of UEA-I positive epithelial cells. To assess binding of alpha(1-2) fucosylated glycans on C. albicans infection, an in vitro adhesion assay was performed with vaginal epithelial cells from wild type and Fut2-null mice. Vaginal epithelial cells from Fut2-null mice were found to bind increased numbers of C. albicans compared to vaginal epithelial cells obtained from wild type mice. Hysterectomy lessened the difference between Fut2-null and wild type mice in binding of C. ablicans in vitro and susceptibility to experimental C. albicans vaginitis in vivo. We generated a recombinant fucosylated MUC1 glycanpolymer to test whether the relative protection of wild type mice compared to Fut2-null mice could be mimicked with exogenous mucin. While a small portion of the recombinant MUC1 epitopes displayed alpha(1-2)fucosylated glycans, the predominant epitopes were sialylated due to endogenous sialyltransferases in the cultured cells. Intravaginal instillation of recombinant MUC1 glycanpolymer partially reduced experimental yeast vaginitis suggesting that a large glycanpolymer, with different glycan epitopes, may affect fungal burden.

  2. Increased luminal mucin does not disturb glucose or ovalbumin absorption in rats fed insoluble dietary fiber.

    PubMed

    Morita, Tatsuya; Tanabe, Hiroki; Ito, Hiroyuki; Yuto, Shunsuke; Matsubara, Takeshi; Matsuda, Tsukasa; Sugiyama, Kimio; Kiriyama, Shuhachi

    2006-10-01

    We tested whether increased mucin secretion due to ingestion of insoluble dietary fiber (IDF) affects small intestinal nutrient absorption in rats. Polystyrene foam (PSF) with a true expansion ratio of 54.9 was used as a model for IDF with high bulk-forming properties. In Expt. 1, rats were fed a control diet or diet containing 50 g PSF/kg for 1, 3, 5, or 7 d. Small intestinal mucin fractions were isolated, and O-linked oligosaccharide chains were measured. The luminal mucin content reached a maximum within 5 d after PSF ingestion. In Expt. 2, rats were fed a control diet or diet containing 50 g PSF/kg for 7 d, and then all rats were switched to the control diet for 1, 3, or 5 d. The increased capacity for luminal mucin secretion disappeared within 5 d after ceasing PSF ingestion. In Expt. 3, rats were fed a control diet or diet containing 70 g PSF/kg for 7 d. Glucose (1g/kg) was administered orally after 12 h of food deprivation. The blood glucose concentrations did not differ between the groups. In Expt. 4, rats were fed a control diet or diet containing 90 g PSF/kg for 14 d. At d 7, portal cannulae were installed. A mixed solution of glucose (1g/kg) and ovalbumin (OVA, 250 mg/kg) was orally administered after 12 h of food deprivation, and responses of portal glucose and OVA concentrations were monitored for 120 min. Although luminal mucin contents were almost doubled in the 9% PSF group compared with the control group, neither portal glucose nor OVA concentration differed at any time point. The results suggest that the short-term ingestion of IDF significantly increases the luminal mucin content, but that this does not disturb nutrient absorption.

  3. Recurrent pure mucinous carcinoma of the breast with mediastinal great vessel invasion: HER-2/neu confers aggressiveness.

    PubMed

    Adair, Jamie D; Harvey, Kyle P; Mahmood, Ali; Caralis, James; Gordon, William; Yanish, Gregory

    2008-02-01

    Mucinous carcinoma of the breast, also known as colloid carcinoma, is a less common variant of breast cancer constituting less than five per cent of breast cancers. We report the case of a 42-year-old premenopausal female who presented with a palpable chest wall recurrence 4 years after simple mastectomy, axillary node dissection, and TRAM flap reconstruction for pure mucinous carcinoma. The recurrent neoplasm was a pure mucinous carcinoma and was found to be invading the mediastinum into the great vessels. The tumor was estrogen receptor positive, progesterone receptor negative, and HER-2/neu positive, which is an unusual finding for mucinous carcinoma. The fact that this tumor demonstrated HER-2/neu positivity may explain the uncharacteristic aggressive nature of this normally indolent type of breast tumor. To our knowledge, this is the first reported case of any mucinous breast cancer invading the mediastinal great vessels and its subsequent en-bloc resection.

  4. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  5. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  6. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  7. The Giant Magnetocaloric Effect

    NASA Astrophysics Data System (ADS)

    Pecharsky, Vitalij K.

    1998-03-01

    Since the discovery of the magnetocaloric effect in pure iron by E.Warburg in 1881, it has been measured experimentally on many magnetic metals and compounds. The majority of the materials studied order magnetically undergoing a second order phase transformation. The magnetocaloric effect, typically peaking near the Curie or the Néel temperature, generally ranges from 0.5 to 2 K (in terms of adiabatic temperature change) or at 1 to 4 J/kg K (in terms of isothermal magnetic entropy change) per 1 T magnetic field change. The giant magnetocaloric effect recently discovered in Gd_5(Si_xGe_1-x)4 alloys, where x <= 0.5, is associated with a first order magnetic phase transition and it reaches values of 3 to 4 K and 6 to 10 J/kg K per 1 T field change, respectively. The refrigerant capacity, which is the measure of how much heat can be transferred from a cold to a hot reservoir in one ideal thermodynamic cycle, is larger than that of the best second order phase transition materials by 25 to 100%. When the Gd_5(Si_xGe_1-x)4 alloys are compared with other known materials, which show first order magnetic phase transition, such as Dy, Ho, Er, HoCo_2, NdMn_2Si_2, Fe_0.49Rh_0.51, and (Hf_0.83Ta_0.17)Fe_2+x, only Fe_0.49Rh_0.51 has comparable magnetocaloric properties. However, the first order magnetic phase transition in Fe_0.49Rh_0.51 is irreversible, and the magnetocaloric effect disappears after one magnetizing/demagnetizing cycle. A study of the crystal structure, thermodynamics, and magnetism of the Gd_5(Si_xGe_1-x)4 alloys, where 0 <= x <= 1 allowed us to obtain a qualitative understanding of the basic relations between the composition, the crystal structure, and the change in thermodynamics and magnetocaloric properties, which occur in the Gd_5(Si_xGe_1-x)4 system, and which brings about the giant magnetocaloric effect when x <= 0.5.

  8. Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Shah, Aalok A.; Campbell, Robert B.; Wan, Kai-tak

    2010-12-01

    Uptake of cytotoxic drugs by typical tumor cells is limited by the dense dendritic network of oligosaccharide mucin chains that forms a mechanical barrier. Atomic force microscopy is used to directly measure the force needed to pierce the mucin layer to reach the cell surface. Measurements are analyzed by de Gennes' steric reptation theory. Multidrug resistant ovarian tumor cells shows significantly larger penetration load compared to the wide type. A pool of pancreatic, lung, colorectal, and breast cells are also characterized. The chemotherapeutic agent, benzyl-α-GalNac, for inhibiting glycosylation is shown to be effective in reducing the mechanical barrier.

  9. Glycoprotein Mucin Molecular Brush on Cancer Cells and its Correlation with Resistance Against Drug Delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Shah, Aalok; Campbell, Robert; Wan, Kai-Tak

    2012-02-01

    Uptake of cytotoxic drugs by typical tumor cells is limited by the dense dendritic network of oligosaccharide mucin chains that forms a mechanical barrier. Atomic force microscopy is used to directly measure the force needed to pierce the mucin layer to reach the cell surface. Measurements are analyzed by deGennes' steric reputation theory. Multi-drug resistant ovarian tumor cells shows significantly larger penetration load compared to the wide type. A pool of pancreatic, lung, colorectal, and breast cells are also characterized. The chemotherapeutic agent, benzyl-α-GalNac, for inhibiting glycosylation is shown to be effective in reducing the mechanical barrier.

  10. Rheology of gastric mucin exhibits a pH-dependent sol-gel transition.

    PubMed

    Celli, Jonathan P; Turner, Bradley S; Afdhal, Nezam H; Ewoldt, Randy H; McKinley, Gareth H; Bansil, Rama; Erramilli, Shyamsunder

    2007-05-01

    Gastric mucin, a high molecular weight glycoprotein, is responsible for providing the gel-forming properties and protective function of the gastric mucus layer. Bulk rheology measurements in the linear viscoelastic regime show that gastric mucin undergoes a pH-dependent sol-gel transition from a viscoelastic solution at neutral pH to a soft viscoelastic gel in acidic conditions, with the transition occurring near pH 4. In addition to pH-dependent gelation behavior in this system, further rheological studies under nonlinear deformations reveal shear thinning and an apparent yield stress in this material which are also highly influenced by pH.

  11. [Appendiceal mucocele due to mucinous cystadenoma: case report and review of the literature].

    PubMed

    Bronzino, P; Abbo, L; Bagnasco, F; Barisone, P; Dezzani, C; Genovese, A M; Iannucci, P; Ippoliti, M; Sacchi, M; Aimo, I

    2006-03-01

    Mucinous cystadenomas of the appendix are rare tumours. In this article we describe the case of a young woman who presented with abdominal pain and a clinical pattern likely to a chronic appendicitis. At laparotomy we found a dilatation of the appendix which contained an abundant quantity of mucus. Histological examination showed a mucinous cystadenoma of the appendix. This neoplasm requires a surgical treatment, usually only appendectomy and right hemicolectomy in case of involvement of the caecum. During operation, the surgeon must take care in handling the appendix because of the risk of rupture with consequent dissemination of epithelial cells in the peritoneal cavity (pseudomyxoma peritonei).

  12. Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

    PubMed Central

    Zhu, Jianhui; Wu, Jing; Pei, Xiucong; Tan, Zhijing; Shi, Jiaqi

    2017-01-01

    Annexins are a multigene family of calcium and phospholipid-binding proteins that play important roles in calcium signaling, cell motility, differentiation and proliferation. Our previous mass spectrometry-based proteomics study revealed that annexin A10 (ANXA10) was uniquely overexpressed in pancreatic CD24+ adenocarcinoma cells that were dissected from clinical PDAC tissues but was absent in CD24- adjacent normal cells. The correlation between ANXA10 expression and the progression of pancreatic cancer remains unknown. In this study, we performed an immunostaining assay to evaluate ANXA10 expression in 155 primary human tissue specimens, including normal pancreas, chronic pancreatitis (CP), pancreatic adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN, the most important precursor of PDAC), and intraductal papillary mucinous neoplasm (IPMN). The immunostaining result showed that ANXA10 was significantly overexpressed in PanINs, IPMNs, and PDACs but negative in normal pancreas and the majority of chronic pancreatitis tissues. Statistical analysis revealed that ANXA10 expression was significantly associated with PDAC and its precursor lesions (p<0.0001). Abundant ANXA10 expression was predominantly present in pancreatic ductal epithelial cells of PanINs, IPMNs, and tumor cells of PDACs. Since PDAC develops through a series of PanINs which in turn arise from pancreatic ducts, the consistent overexpression of ANXA10 in ductal epithelial cells in PanINs and PDACs but negative in normal pancreatic ducts suggests that ANXA10 could serve as a potential marker indicating the presence of PDAC at its earliest precancerous stages. Double immunostaining of ANXA10 and CD24 showed that there was a large overlap between these two markers in PDAC and high-grade neoplasia lesions. The statistical analysis showed that the coexpression of ANXA10 and CD24 was significantly correlated with the progression of pancreatic precursor lesions towards PDACs. PMID:28369074

  13. A unique advantage for giant eyes in giant squid.

    PubMed

    Nilsson, Dan-Eric; Warrant, Eric J; Johnsen, Sönke; Hanlon, Roger; Shashar, Nadav

    2012-04-24

    Giant and colossal deep-sea squid (Architeuthis and Mesonychoteuthis) have the largest eyes in the animal kingdom [1, 2], but there is no explanation for why they would need eyes that are nearly three times the diameter of those of any other extant animal. Here we develop a theory for visual detection in pelagic habitats, which predicts that such giant eyes are unlikely to evolve for detecting mates or prey at long distance but are instead uniquely suited for detecting very large predators, such as sperm whales. We also provide photographic documentation of an eyeball of about 27 cm with a 9 cm pupil in a giant squid, and we predict that, below 600 m depth, it would allow detection of sperm whales at distances exceeding 120 m. With this long range of vision, giant squid get an early warning of approaching sperm whales. Because the sonar range of sperm whales exceeds 120 m [3-5], we hypothesize that a well-prepared and powerful evasive response to hunting sperm whales may have driven the evolution of huge dimensions in both eyes and bodies of giant and colossal squid. Our theory also provides insights into the vision of Mesozoic ichthyosaurs with unusually large eyes.

  14. Formation of the giant planets

    NASA Technical Reports Server (NTRS)

    Lissauer, Jack J.

    2006-01-01

    The observed properties of giant planets, models of their evolution and observations of protoplanetary disks provide constraints on the formation of gas giant planets. The four largest planets in our Solar System contain considerable quantities of hydrogen and helium, which could not have condensed into solid planetesimals within the protoplanetary disk. All three (transiting) extrasolar giant planets with well determined masses and radii also must contain substantial amounts of these light gases. Jupiter and Saturn are mostly hydrogen and helium, but have larger abundances of heavier elements than does the Sun. Neptune and Uranus are primarily composed of heavier elements. HD 149026 b, which is slightly more massive than is Saturn, appears to have comparable quantities of light gases and heavy elements. HD 209458 b and TrES-1 are primarily hydrogen and helium, but may contain supersolar abundances of heavy elements. Spacecraft flybys and observations of satellite orbits provide estimates of the gravitational moments of the giant planets in our Solar System, which in turn provide information on the internal distribution of matter within Jupiter, Saturn, Uranus and Neptune. Atmospheric thermal structure and heat flow measurements constrain the interior temperatures of planets. Internal processes may cause giant planets to become more compositionally differentiated or alternatively more homogeneous; high-pressure laboratory .experiments provide data useful for modeling these processes. The preponderance of evidence supports the core nucleated gas accretion model. According to this model, giant planets begin their growth by the accumulation of small solid bodies, as do terrestrial planets. However, unlike terrestrial planets, the growing giant planet cores become massive enough that they are able to accumulate substantial amounts of gas before the protoplanetary disk dissipates. The primary questions regarding the core nucleated growth model is under what conditions

  15. Clump Giants in the Hyades

    NASA Technical Reports Server (NTRS)

    Mushotzky, Richard F. (Technical Monitor); Brickhouse, Nancy

    2003-01-01

    The project is entitled 'Clump Giants in the Hyades.' This observation of one of the late-type Hyades giants (Gamma Tau) has implications for understanding the formation of late-type stellar coronae as a function of the evolutionary state of the star. The Hyades giants are interesting because they are all clump giants in the Helium burning phase, similar to the cool primary of Capella. The Hyades giants show significantly more magnetic activity than expected from their state of evolution (and slowed-down rotation). Thus these systems provide an important clue to dynamo action. The data were obtained by the satellite on 13 March 2001 for a total RGS exposure of 58220 seconds. These data were delivered to the PI on 7 August 2001. The data could not be reprocessed until SAS Version 5.3.3 which became available 7 June 2002. Although the guidelines for assessing background rates suggested that half the data were contaminated, it does not appear that the spectral region of the RGS was adversely affected by unusually high background. The spectra show strong lines of Fe XVII and XVIII, O VII and VIII, Ne IX and X, along with numerous weaker lines. The emission measure distribution is highly reminiscent of Capella; if anything, the emission measure distribution is steeper at 6 million K than for Capella. Gamma Tau is the second brightest of the Hyades clump giants. Pallavicini et al. have shown that the luminosity of the brightest Hyades giant (Theta Tau) is remarkably similar to its luminosity as measured by Einstein. Short-term variability is also modest. We are addressing the variability issue now for Gamma Tau. Initial results were reported at the 2003 Seattle AAS meeting. A paper is in preparation for submission to the Astrophysical Journal.

  16. Correlation of p53 Overexpression with the Clinicopathological Prognostic Factors in Colorectal Adenocarcinoma

    PubMed Central

    Akshatha C; Mysorekar, Vijaya; Arundhathi S; Raj, Adithi; Shetty, Smitha

    2016-01-01

    Introduction Mutation in p53 gene and accumulation of p53 protein is a common genetic event in colorectal carcinomas. p53 mutation can be detected by various techniques such as DNA sequencing, polymerase chain reaction and immunohistochemistry (IHC). However, IHC is simple and is consistent with other techniques. Aim To establish a correlation between overexpression of p53 with the clinical features, tumour histopathology and stage of Colorectal Carcinoma (CRC). Materials and Methods This prospective and retrospective study of clinical, histopathological and IHC features of CRC was conducted on colectomy and abdomino-perineal resection specimens received from January 2008 to June 2013. For each case, the clinical features, tumour morphology and p53 status (by IHC) were evaluated. Results The most common histologic type of CRC was Non-Specific Type (NST) and grade II tumours were seen predominantly (60%). Overall, 67.5% of CRCs showed p53 positivity on IHC. Intense p53 positivity was observed in 37.5% of CRCs of NST type and 33.3% of mucinous adenocarcinomas showed moderate positivity. Grade III tumours showed variable p53 positivity and those with lymph node metastasis showed moderate (55.6%) or intense positivity (53.8%). But there was no statistically significant correlation of p53 status and various clinicopathological prognostic factors. Conclusion As p53 protein overexpression is seen in a relatively high percentage of CRCs, it seems that p53 mutation plays an important role in development of CRC. However, no direct correlation could be established between p53 results and the patients’ age, sex, tumour site, size, histological type, grade, lymph node status, or TNM stage. A prolonged follow up is necessary to conclude whether p53 status has any influence on the long, term prognosis and patient survival. PMID:28208862

  17. Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma.

    PubMed

    Zenali, Maryam; Overman, Michael J; Rashid, Asif; Broaddus, Russell B; Wang, Hua; Katz, Matthew H; Fleming, Jason B; Abbruzzese, James L; Wang, Huamin

    2013-12-01

    Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.

  18. Open questions about giant viruses.

    PubMed

    Claverie, Jean-Michel; Abergel, Chantal

    2013-01-01

    The recent discovery of giant viruses exhibiting double-stranded DNA genomes larger than a million base pairs, encoding more than a thousand proteins and packed in near micron-sized icosahedral particles, opened a new and unexpected chapter in virology. As of today, these giant viruses and their closest relatives of lesser dimensions infect unicellular eukaryotes found in aquatic environments, but belonging to a wide diversity of early branching phyla. This broad phylogenetic distribution of hosts is consistent with the hypothesis that giant viruses originated prior to the radiation of the eukaryotic domain and/or might have been involved in the partition of nuclear versus cytoplasmic functions in ancestral cells. The distinctive features of the known giant viruses, in particular the recurrent presence of components of the translation apparatus in their proteome, raise a number of fundamental questions about their origin, their mode of evolution, and the relationship they may entertain with other dsDNA viruses, the genome size of which exhibits the widest distribution among all biological entities, from less than 5 kb to more than 1.25 Mb (a ratio of 1:250). At a more conceptual level, the convergence between the discovery of increasingly reduced parasitic cellular organisms and that of giant viruses exhibiting a widening array of cellular-like functions may ultimately abolish the historical discontinuity between the viral and the cellular world.

  19. Giant Magellan Telescope: overview

    NASA Astrophysics Data System (ADS)

    Johns, Matt; McCarthy, Patrick; Raybould, Keith; Bouchez, Antonin; Farahani, Arash; Filgueira, Jose; Jacoby, George; Shectman, Steve; Sheehan, Michael

    2012-09-01

    The Giant Magellan Telescope (GMT) is a 25-meter optical/infrared extremely large telescope that is being built by an international consortium of universities and research institutions. It will be located at the Las Campanas Observatory, Chile. The GMT primary mirror consists of seven 8.4-m borosilicate honeycomb mirror segments made at the Steward Observatory Mirror Lab (SOML). Six identical off-axis segments and one on-axis segment are arranged on a single nearly-paraboloidal parent surface having an overall focal ratio of f/0.7. The fabrication, testing and verification procedures required to produce the closely-matched off-axis mirror segments were developed during the production of the first mirror. Production of the second and third off-axis segments is underway. GMT incorporates a seven-segment Gregorian adaptive secondary to implement three modes of adaptive-optics operation: natural-guide star AO, laser-tomography AO, and ground-layer AO. A wide-field corrector/ADC is available for use in seeing-limited mode over a 20-arcmin diameter field of view. Up to seven instruments can be mounted simultaneously on the telescope in a large Gregorian Instrument Rotator. Conceptual design studies were completed for six AO and seeing-limited instruments, plus a multi-object fiber feed, and a roadmap for phased deployment of the GMT instrument suite is being developed. The partner institutions have made firm commitments for approximately 45% of the funds required to build the telescope. Project Office efforts are currently focused on advancing the telescope and enclosure design in preparation for subsystem- and system-level preliminary design reviews which are scheduled to be completed in the first half of 2013.

  20. Abiraterone Acetate and Castration Resistant Ductal Adenocarcinoma of the Prostate

    PubMed Central

    Linden-Castro, Edgar; Pelayo-Nieto, Marcela; Alias-Melgar, Alejandro; Espinosa-Perezgrovas, Daniel; Ramirez-Galindo, Ivan; Catalan-Quinto, Gabriel

    2014-01-01

    Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate. PMID:24891969

  1. Primary Adenocarcinoma of an Ileostomy in Crohn's Disease

    PubMed Central

    Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.

    2016-01-01

    Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature. PMID:27622191

  2. [Secondary neoplasms of the larynx from a colonic adenocarcinoma].

    PubMed

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-26

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was treated with endoscopic surgery and radiation.

  3. Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

    PubMed

    Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

    2014-01-01

    Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening.

  4. Biomarkers in pancreatic adenocarcinoma: current perspectives

    PubMed Central

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

  5. Preclinical models of pancreatic ductal adenocarcinoma.

    PubMed

    Hwang, Chang-Il; Boj, Sylvia F; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA.

  6. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    NASA Astrophysics Data System (ADS)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  7. Comparative proteomic label-free analysis of Campylobacter jejuni NCTC 11168 cultured with porcine mucin.

    PubMed

    Hong, Sahyun; Cha, Injun; Kim, Nan-Ok; Seo, Jong-Bok; Kim, Soo-Young; Kim, Jong-Hyun; Chung, Gyung Tae; Jeon, Byeonghwa; Kang, Yeon-Ho

    2014-03-01

    Campylobacter jejuni is a major gastrointestinal pathogen in humans. Poultry is a primary reservoir for C. jejuni, and C. jejuni appears to be highly adapted to the gastrointestinal tracts of avian species. We determined the protein expression profiles of C. jejuni NCTC 11168 cultured in medium containing porcine mucin. Differentially expressed proteins in the presence and absence of porcine mucin were identified using the label-free method. We identified 52 proteins with expression that was either upregulated (32 proteins) or downregulated (20 proteins) by porcine mucin. These proteins are involved in diverse cellular functions, such as motility, cell wall synthesis, iron transport, energy production, and amino acid metabolism. In particular, the upregulated proteins were involved in chemotaxis (CheV and CetA), motility (FlaA), colonization and adherence (CadF, FrdA, CfrA, MapA, and HydA), and stress tolerance (TrxB and ClpB). These results suggest that C. jejuni changes its protein expression in response to porcine mucin and that this change in expression may contribute to host adaptation of C. jejuni NCTC 11168.

  8. Prebiotic galactooligosaccharides activate mucin and pectic galactan utilization pathways in the human gut symbiont Bacteroides thetaiotaomicron

    PubMed Central

    Lammerts van Bueren, Alicia; Mulder, Marieke; Leeuwen, Sander van; Dijkhuizen, Lubbert

    2017-01-01

    Galactooligosaccharides (GOS) are prebiotic carbohydrates that impart changes in the gut bacterial composition of formula-fed infants to more closely resemble that of breast-fed infants. Consuming human milk oligosaccharides (HMOs) provides specific bacterial strains with an advantage for colonizing the infant intestine. These same effects are seen in infants after GOS consumption, however GOS are very complex mixtures and the underlying molecular mechanisms of how GOS mimic HMOs are relatively unknown. Here we studied the effects of GOS utilization on a prominent gut symbiont, Bacteroides thetaiotaomicron, which has been previously shown to consume HMOs via mucin O-glycan degradation pathways. We show that several pathways for targeting O-mucin glycans are activated in B. thetaiotaomicron by GOS, as well as the galactan utilization sytem. Characterization of the endo-galactanase from this system identified activity on various longer GOS substrates while a subset of GOS compounds were identified as potential activators of mucin glycan metabolism in B. thetaiotaomicron. Our results show that GOS functions as an inducer of mucin-glycan pathways while providing a nutrient source in the form of β-(1 → 4)-galactan. These metabolic features of GOS mixtures may serve to explain the beneficial effects that are seen for GOS supplemented infant formula. PMID:28091546

  9. Specific Glycoforms of MUC5AC and Endorepellin Accurately Distinguish Mucinous from Nonmucinous Pancreatic Cysts*

    PubMed Central

    Cao, Zheng; Maupin, Kevin; Curnutte, Bryan; Fallon, Brian; Feasley, Christa L.; Brouhard, Elizabeth; Kwon, Richard; West, Christopher M.; Cunningham, John; Brand, Randall; Castelli, Paola; Crippa, Stefano; Feng, Ziding; Allen, Peter; Simeone, Diane M.; Haab, Brian B.

    2013-01-01

    Specific protein glycoforms may be uniquely informative about the pathological state of a cyst and may serve as accurate biomarkers. Here we tested that hypothesis using antibody-lectin sandwich arrays in broad screens of protein glycoforms and in targeted studies of candidate markers. We profiled 16 different glycoforms of proteins captured by 72 different antibodies in cyst fluid from mucinous and nonmucinous cysts (n = 22), and we then tested a three-marker panel in 22 addition samples and 22 blinded samples. Glycan alterations were not widespread among the proteins and were mainly confined to MUC5AC and endorepellin. Specific glycoforms of these proteins, defined by reactivity with wheat germ agglutinin and a blood group H antibody, were significantly elevated in mucinous cysts, whereas the core protein levels were not significantly elevated. A three-marker panel based on these glycoforms distinguished mucinous from nonmucinous cysts with 93% accuracy (89% sensitivity, 100% specificity) in a prevalidation sample set (n = 44) and with 91% accuracy (87% sensitivity, 100% specificity) in independent, blinded samples (n = 22). Targeted lectin measurements and mass spectrometry analyses indicated that the higher wheat germ agglutinin and blood group H reactivity was due to oligosaccharides terminating in GlcNAc or N-acetyl-lactosamine with occasional α1,2-linked fucose. The results show that MUC5AC and endorepellin glycoforms may be highly specific and sensitive biomarkers for the differentiation of mucinous from nonmucinous pancreatic cysts. PMID:23836919

  10. Hagfish slime and mucin flow properties and their implications for defense

    NASA Astrophysics Data System (ADS)

    Böni, Lukas; Fischer, Peter; Böcker, Lukas; Kuster, Simon; Rühs, Patrick A.

    2016-07-01

    When hagfish (Myxinidae) are attacked by predators, they form a dilute, elastic, and cohesive defensive slime made of mucins and protein threads. In this study we propose a link between flow behavior and defense mechanism of hagfish slime. Oscillatory rheological measurements reveal that hagfish slime forms viscoelastic networks at low concentrations. Mucins alone did not contribute viscoelasticity, however in shear flow, viscosity was observed. The unidirectional flow, experienced by hagfish slime during suction feeding by predators, was mimicked with extensional rheology. Elongational stresses were found to increase mucin viscosity. The resulting higher resistance to flow could support clogging of the attacker’s gills. Shear flow in contrast decreases the slime viscosity by mucin aggregation and leads to a collapse of the slime network. Hagfish may benefit from this collapse when trapped in their own slime and facing suffocation by tying a sliding knot with their body to shear off the slime. This removal could be facilitated by the apparent shear thinning behavior of the slime. Therefore hagfish slime, thickening in elongation and thinning in shear, presents a sophisticated natural high water content gel with flow properties that may be beneficial for both, defense and escape.

  11. Intestinal metaplasia of appendiceal endometriosis is not uncommon and may mimic appendiceal mucinous neoplasm.

    PubMed

    Vyas, Monika; Wong, Serena; Zhang, Xuchen

    2017-01-01

    Endometriosis of the appendix can be an incidental finding or a cause of appendicitis, intussusception, perforation or retention mucocele. Intestinal metaplasia of appendiceal endometriosis may occur, which can lead to a misdiagnosis of low-grade appendiceal mucinous neoplasm. On a retrospective search of the pathology database from 2001 to 2015, we identified 78 appendiceal endometriosis cases and intestinal metaplasia was present in 10/78 (13%) cases. In most of the cases (90%), the foci of intestinal metaplasia were mainly localized close to the mucosa. Intestinal and endometrial hybrid glands were present in 9/10 (90%) cases. These cases were often associated with marked appendiceal distortion, luminal obliteration and mass formation, causing concern for a mucinous neoplasm clinically and pathologically. Our findings indicate that intestinal metaplasia in appendiceal endometriosis is not an uncommon phenomenon, which can be mistaken for a mucinous neoplasm. Endometriosis should be kept in mind when a diagnosis of appendiceal mucinous neoplasm is made, especially in a young woman with a clinical history of endometriosis.

  12. Niflumic acid inhibits ATP-stimulated exocytosis in a mucin-secreting epithelial cell line.

    PubMed

    Bertrand, C A; Danahay, H; Poll, C T; Laboisse, C; Hopfer, U; Bridges, R J

    2004-02-01

    ATP is an efficacious secretagogue for mucin and chloride in the epithelial cell line HT29-Cl.16E. Mucin release has been measured as [3H]glucosamine-labeled product in extracellular medium and as single-cell membrane capacitance increases indicative of exocytosis-related increases in membrane area. The calcium-activated chloride channel blocker niflumic acid, also reported to modulate secretion, was used to probe for divergence in the purinergic signaling of mucin exocytosis and channel activation. With the use of whole cell patch clamping, ATP stimulated a transient capacitance increase of 15 +/- 4%. Inclusion of niflumic acid significantly reduced the ATP-stimulated capacitance change to 3 +/- 1%, although normalized peak currents were not significantly different. Ratiometric imaging was used to assess intracellular calcium (Cai2+) dynamics during stimulation. In the presence of niflumic acid, the ATP-stimulated peak change in Cai2+ was unaffected, but the initial response and overall time to Cai2+ peak were significantly affected. Excluding external calcium before ATP stimulation or including the capacitative calcium entry blocker LaCl3 during stimulation muted the initial calcium transient similar to that observed with niflumic acid and significantly reduced peak capacitance change, suggesting that a substantial portion of the ATP-stimulated mucin exocytosis in HT29-Cl.16E depends on a rapid, brief calcium influx through the plasma membrane. Niflumic acid interferes with this influx independent of a chloride channel blockade effect.

  13. Pilus-Mediated Adherence of Haemophilus influenzae to Human Respiratory Mucins

    PubMed Central

    Kubiet, Martin; Ramphal, Reuben; Weber, Allan; Smith, Arnold

    2000-01-01

    Haemophilus influenzae, especially the nontypeable strains, are among the most common pathogens encountered in patients with chronic lung disease and otitis media. We and others have demonstrated that respiratory isolates of nontypeable H. influenzae bind to human mucins, but the mechanism of binding is not entirely clear. We have therefore examined the role of pili in the adherence of both type b and nontypeable H. influenzae to human respiratory mucins. We used isogenic H. influenzae strains with a mutation in the structural gene for pilin (hifA), a laboratory H. influenzae strain transformed with a type b pilus gene cluster (from strain C54), antibodies raised against H. influenzae HifA, and Escherichia coli strains carrying a cloned type b pilus gene cluster (from strain AM30) in these studies. All bacteria lacking HifA or the pilus gene cluster had decreased adherence of piliated H. influenzae to mucins, and Fab fragments of anti-HifA antibodies inhibited the adherence. E. coli strains carrying the cloned type b pilus gene cluster were six to seven times more adhesive than strains carrying the vector. The role of other putative adhesins was not examined and thus cannot be excluded, but these studies support a role for pili in the binding of H. influenzae to human respiratory mucins. PMID:10816486

  14. Cleaning of Filtering Facepiece Respirators Contaminated with Mucin and Staphylococcus aureus

    DTIC Science & Technology

    2012-11-01

    two of which contain antimicrobial agents (hypochlorite and benzalkonium chloride (BAC)). Prior to extraction and quantification of the...aerosols of mucin or viable Staphylococcus aureus then cleaned with hypochlorite, benzalkonium chloride , or nonantimicrobial wipes. After cleaning, FFRs...which contain benzalkonium chloride (BAC); Hype Wipes (Current Technologies, Inc, Crawfordsville, IN),16 which contain 0.9% hypochlorite (OCL); and

  15. Hagfish slime and mucin flow properties and their implications for defense

    PubMed Central

    Böni, Lukas; Fischer, Peter; Böcker, Lukas; Kuster, Simon; Rühs, Patrick A.

    2016-01-01

    When hagfish (Myxinidae) are attacked by predators, they form a dilute, elastic, and cohesive defensive slime made of mucins and protein threads. In this study we propose a link between flow behavior and defense mechanism of hagfish slime. Oscillatory rheological measurements reveal that hagfish slime forms viscoelastic networks at low concentrations. Mucins alone did not contribute viscoelasticity, however in shear flow, viscosity was observed. The unidirectional flow, experienced by hagfish slime during suction feeding by predators, was mimicked with extensional rheology. Elongational stresses were found to increase mucin viscosity. The resulting higher resistance to flow could support clogging of the attacker’s gills. Shear flow in contrast decreases the slime viscosity by mucin aggregation and leads to a collapse of the slime network. Hagfish may benefit from this collapse when trapped in their own slime and facing suffocation by tying a sliding knot with their body to shear off the slime. This removal could be facilitated by the apparent shear thinning behavior of the slime. Therefore hagfish slime, thickening in elongation and thinning in shear, presents a sophisticated natural high water content gel with flow properties that may be beneficial for both, defense and escape. PMID:27460842

  16. Histology and mucin histochemistry of the digestive tract of yellow catfish, Pelteobagrus fulvidraco.

    PubMed

    Cao, X J; Wang, W M

    2009-08-01

    The histology and characteristics of mucins secreted by epithelial mucous cells of the digestive tract in yellow catfish, Pelteobagrus fulvidraco were investigated using light microscope and transmission electron microscope. The digestive tract was divided into a pharynx, oesophagus, U-shaped stomach (with a cardiac, fundic and pyloric part) and intestine, composed of anterior intestine, middle intestine and posterior intestine, which consisted of a mucosa (epithelial layer), lamina propria-submucosa, muscularis and serosa. A large number of isolated longitudinal striated muscular bundles were present in the lamina propria-submucosa of pharynx. Goblet cells were observed throughout the digestive tract, except in the stomach. In the cardiac and fundic stomach, a plenty of gastric glands were observed, whereas they were absent in the pyloric part. Numerous mitochondria and endoplasmic reticulum were observed in the columnar epithelial cells of the intestine, especially of the anterior part. The epithelial mucous cells contained neutral or other two mixtures of acid and neutral mucins, the first being the most common. The neutral mucin was the only type of mucins in the stomach, anterior intestine and middle intestine. The results of this study will be helpful for understanding the digestive physiology and diagnosing some gastrointestinal diseases in yellow catfish.

  17. Mucin biosynthesis in the bovine goblet cell induced by Cooperia oncophora infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mucin hypersecretion is considered to be one of the most common components of the immune response to gastrointestinal nematode infection. However, investigations have not been conducted in the Cattle-Cooperia oncophora system to verify the findings largely derived from murine models. In this study, ...

  18. Malonic acid suppresses mucin-type O-glycan degradation during hydrazine treatment of glycoproteins.

    PubMed

    Goso, Yukinobu

    2016-03-01

    Hydrazine treatment is frequently used for releasing mucin-type O-glycans (O-glycans) from glycoproteins because the method provides O-glycans that retain a reducible GalNAc at their reducing end, which is available for fluorescent labeling. However, many O-glycans are degraded by "peeling" during this treatment. In the current study, it was found that malonic acid suppressed O-glycan degradation during hydrazine treatment of bovine fetuin or porcine gastric mucin in both the gas and liquid phases. This is paradoxical because the release of O-glycans from glycoproteins occurs under alkaline conditions. However, malonic acid seems to prevent the degradation through its acidic property given that other weak acids also prevented the degradation. Accordingly, disodium malonate did not suppress O-glycan degradation. Application of this method to rat gastric mucin demonstrated that the majority of the major O-glycans obtained in the presence of malonic acid were intact, whereas those obtained in the absence of malonic acid were degraded. These results suggest that hydrazine treatment in the presence of malonic acid would allow glycomic analysis of native mucin glycoproteins.

  19. Synthesis of oxime-linked mucin mimics containing thetumor-related TN and sialyl TN antigens

    SciTech Connect

    Marcaurelle, Lisa A.; Shin, Youngsook; Goon, Scarlett; Bertozzi,Carolyn R.

    2001-08-21

    The synthesis of oxime-linked mucin mimics was accomplished via the incorporation of multiple ketone residues into a peptide followed by reaction with aminooxy sugars corresponding to the tumor-related T{sub N} and sialyl T{sub N} (ST{sub N}) antigens.

  20. [A Case of Pure Type Mucinous Carcinoma Recurrence after Local Control].

    PubMed

    Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2015-11-01

    The patient was a 44-year-old woman. Mastectomy and sentinel lymph node biopsy had been performed for carcinoma of the left breast approximately 1 year previously. The diagnosis was mucinous carcinoma, T3N0M0, stage ⅡB, ER(+), PgR(+), HER2 score 0, Ki-67 20%. Hormone therapy was administered postoperatively. Four months after the surgery, left axilla lymphadenopathy was observed. Chemotherapy with EC and nab-PTX was started for the postoperative lymph node recurrence. To achieve local control, axillary lymphadenectomy was performed within 1 year postoperatively, and 1 metastatic lesion in the lymph nodes was observed. Hormone therapy was started sequentially, with no subsequent recurrence or metastasis. Mucinous carcinomas are classified as a breast cancer subtype. Mixed type, including breast ductal carcinoma, form a large proportion of mucinous carcinomas and the therapy for breast ductal carcinoma is usually administered in such cases. Conversely, pure type mucinous carcinomas rarely show metastasis and have a good prognosis. In this case, however, metastasis was noted and chemotherapy was not completely effective, and local control was achieved with surgical resection.

  1. Sonographic and pathologic image analysis of pure mucinous carcinoma of the breast.

    PubMed

    Kaoku, Setsuko; Konishi, Eiichi; Fujimoto, Yasuhisa; Tohno, Eriko; Shiina, Tsuyoshi; Kondo, Kengo; Yamazaki, Sanae; Kajihara, Mariko; Shinkura, Nobuhiko; Yanagisawa, Akio

    2013-07-01

    The aims of this study were to elucidate sonographic and histologic features of pure mucinous carcinoma (P-MC) of the breast using quantitative analysis and to evaluate the relationship between quantitative analysis and visual qualitative assessment. Eleven P-MCs (nine patients) were evaluated qualitatively and quantitatively. Three experts assessed these sonographic images using the Breast Imaging Reporting and Data System (BI-RADS) lexicon. For assessment of internal echoes and posterior echoes, quantitative measures were determined using ImageJ software. Histologic thin sections were stained for classification into separate parts of the tumor (stroma, mucin and cancer cells) and were digitized. Internal echoes were isoechoic in 7 of 11 (63.6%) tumors and hypoechoic in 4 of 11 (36.4%); all P-MCs were "enhanced" in qualitative evaluation. As internal echoes increased, the proportion of stroma increased and that of mucin decreased. The high level of internal echoes is correlated with reflection and back-scattering, which are caused mainly by the interface between mucin and stroma.

  2. Pure mucinous carcinoma with axillary lymph node metastasis in a male breast.

    PubMed

    Dragoumis, Dimitrios M; Assimaki, Anthoula S; Tsiftsoglou, Aris P

    2012-10-01

    Pure mucinous carcinoma of the male breast is an extremely uncommon malignant breast neoplasm and usually occurs at advanced age. It is characterized by a higher degree of mucus production, a more benign behavior, a lower incidence of metastatic nodal involvement, and a subsequent higher survival rate. We describe such a case of a 59-year-old male, who displayed a gradually growing retroareolar tumor of the right breast. The tumor was well demarcated and had a soft consistency with a gelatinous appearance. Based on the preoperative clinical identification of right axillary lymphadenopathy, the patient eventually underwent right modified radical mastectomy and right axillary nodal dissection. Regarding histological findings, the neoplasm corresponded to a pure mucinous carcinoma with axillary lymph node metastasis. Although lymph node metastasis of pure mucinous carcinoma of the breast is rare, it is essential to perform careful clinical examination when the primary breast mass is suspicious for mucinous carcinoma, because the presence of axillary lymphadenopathy will subsequently define the proper choice of therapeutic strategy.

  3. Nuclear staining of fgfr-2/stat-5 and runx-2 in mucinous breast cancer.

    PubMed

    May, María; Mosto, Julián; Vazquez, Paula Martinez; Gonzalez, Pedro; Rojas, Paola; Gass, Hugo; Lanari, Claudia; Molinolo, Alfredo A

    2016-02-01

    Mucinous carcinoma (MBC) is a rare subtype of breast cancer characterized by the production of variable amounts of mucin, with a prognosis better than that of non-mucinous carcinomas (NMBC). The aim of this project was to evaluate the expression of STAT-5, RUNX-2, and FGFR-2 in a cohort of MBC and compare it with that of NMBC using standard immunohistochemistry. STAT-5 and RUNX-2 are two transcription factors with cytoplasmic and/or nuclear localization that have been related to FGFR-2, a tyrosine kinase growth factor receptor that can interact with STAT-5 and with PR in the nuclei of breast cancer cells. Membranous, cytoplasmic, and nuclear staining were evaluated and expressed as the percentage of stained cells (0-100%) multiplied by the staining intensity (0-3), thus obtaining an index ranging from 0 to 300. Nuclear and/or cytoplasmic immunoreactivity of the three proteins were detected in a high number of NMBC. Nuclear FGFR-2 staining correlated with nuclear STAT-5 (p<0.05) and nuclear RUNX-2 (p<0.01) in both tumor types; however MBC had a significant higher expression of nuclear FGFR-2 (p<0.01) and RUNX-2 (p<0.05) than that of NMBC, and displayed positive immunoreactivity of the 3 proteins in 70.8% of the cases. These results suggest that these proteins may have a role in the progression of the mucinous phenotype, in which nuclear STAT-5 may inhibit RUNX-2 prometastatic effect.

  4. Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells

    SciTech Connect

    Kuan, S.F.; Byrd, J.C.; Basbaum, C.; Kim, Y.S. )

    1989-11-15

    Specific inhibitors of the glycosylation of O-glycosidically linked glycoproteins have not previously been described. When tested for their effects on mucin glycosylation in a mucin-producing colon cancer cell line, LS174T, benzyl-, phenyl-, and p-nitrophenyl-N-acetyl-alpha-galactosaminide inhibited the formation of fully glycosylated mucin in a dose-dependent manner. Free aryl-oligosaccharides were found in the medium of treated cells labeled with ({sup 3}H)glucosamine, ({sup 3}H)galactose, ({sup 3}H)fucose, ({sup 3}H)mannosamine, or phenyl-alpha-(6-{sup 3}H) N-acetylgalactosamine. UDP-Gal:GalNAc-beta 1,3-galactosyltransferase was inhibited by aryl-N-acetyl-alpha-galactosaminides but not by a number of other aryl-glycosides. Treatment with these inhibitors also causes reversible morphologic changes including formation of intercellular cysts. Aryl-N-acetyl-alpha-galactosaminides can be useful for the structural and functional studies of mucin macromolecules and other O-linked glycoproteins.

  5. Histological and mucin histochemical study of the small intestine of the Persian squirrel (Sciurus anomalus).

    PubMed

    Tootian, Zahra; Sadeghinezhad, Javad; Sheibani, Mohammad Taghi; Fazelipour, Simin; De Sordi, Nadia; Chiocchetti, Roberto

    2013-01-01

    This article describes the histological and mucin histochemical properties of the small intestine of the Persian squirrel (Sciurus anomalus). This species is widely distributed in the Middle East and can be found as a companion animal. The histological studies revealed that the plicae circulares were not visible in the tunica mucosa. The maximum height and width of the villi were observed in the duodenum, which then decreased toward the ileum. The muscularis mucosa was scattered, whereas the tunica submucosa was composed of dense connective tissue. The lymphatic nodules were seen in the submucosa of the distal part of the jejunum and ileum, and Brunner's glands were embedded in the initial portion of the duodenum. The tunica muscularis was significantly thicker in the ileum, and the circular muscle layer was thicker than the longitudinal muscle layer throughout the entire length of the small intestine. The mucin histochemistry, which was examined using the periodic acid-Schiff (PAS) and alcian blue (AB) (pH 1.0 and 2.5) and also PAS-AB (pH 2.5) and aldehyde fuchsin-AB (pH 2.5) techniques coupled with methylation and saponification reaction for some sections, showed that the small intestine mucous content included both carboxylated and sulfated acidic mucins with few neutral mucins. The results of this study contribute to the knowledge of the histological and histochemical characteristics of the gastrointestinal tracts of exotic mammals and provide data for comparison with other mammals.

  6. The Role of Mucin-type O-glycans in Eukaryotic Development

    PubMed Central

    Tabak, Lawrence A.

    2010-01-01

    Newly emerging genetic studies have revealed that a subset of the family of glycosyltransferases responsible for the formation of mucin-type O glycans is essential for normal development. As additional genetic, biochemical and physical tools are developed to interrogate the complex structure and surface location of this under-studied class of carbohydrate, no doubt additional roles will be elucidated. PMID:20144722

  7. Polymyalgia Rheumatica and Giant Cell Arteritis

    MedlinePlus

    ... Clinical Trial Journal Articles Polymyalgia Rheumatica and Giant Cell Arteritis May 2016 Questions and Answers about Polymyalgia Rheumatica and Giant Cell Arteritis This publication contains general information about polymyalgia ...

  8. Adhesive properties, extracellular protein production, and metabolism in the Lactobacillus rhamnosus GG strain when grown in the presence of mucin.

    PubMed

    Sanchez, Borja; Saad, Naima; Schmitter, Jean-Marie; Bressollier, Philippe; Urdaci, Maria C

    2010-06-01

    This paper examines the probiotic bacterium Lactobacillus rhamnosus GG, and how it reacts to the presence of mucin in its extracellular milieu. Parameters studied included cell clustering, adhesion to mucin, extracellular protein production, and formation of final metabolites. L. rhamnosus GG was found to grow efficiently in the presence of glucose, N-acetylglucosamine, or mucin (partially purified or purified) as sole carbon sources. However, it was unable to grow using other mucin constituents, such as fucose or glucuronic acid. Mucin induced noticeable changes in all the parameters studied when compared with growth using glucose, including in the formation of cell clusters, which were easily disorganized with trypsin. Mucin increased adhesion of the bacterium, and modulated the production of extracellular proteins. SDS-PAGE revealed that mucin was not degraded during L. rhamnosus GG growth, suggesting that this bacterium is able to partially use the glucidic moiety of glycoprotein. This study goes some way towards developing an understanding of the metabolic and physiological changes that L. rhamnosus GG undergoes within the human gastrointestinal tract.

  9. Improved method for immunostaining of mucin separated by supported molecular matrix electrophoresis by optimizing the matrix composition and fixation procedure.

    PubMed

    Matsuno, Yu-Ki; Dong, Weijie; Yokoyama, Seiya; Yonezawa, Suguru; Saito, Takuro; Gotoh, Mitsukazu; Narimatsu, Hisashi; Kameyama, Akihiko

    2011-07-01

    Mucins are a family of heavily glycosylated high molecular mass proteins that have great potential as novel clinical biomarkers for the diagnosis of various malignant tumors. Supported molecular matrix electrophoresis (SMME) is a new type of membrane electrophoresis that can be used to characterize mucins. In SMME, mucins migrate in a molecular matrix supported by membrane materials. Here, we have developed an immunostaining method for the identification of SMME-separated mucins. The novel method involves stably fixing the mucins onto the SMME membrane and optimizing the molecular matrix for the fixation process. We applied this technique for the detection of MUC1 produced from three cancer cell lines (T47D, HPAF-II and BxPC3) and also analyzed their O-linked glycans by mass spectrometry. Our results revealed that properties of the MUC1 molecules from the three cell lines are different in terms of migrating position in SMME and glycan profile. The present method allows simple and rapid characterization of mucins in terms of both glycans and core proteins. The method will be a useful tool for the exploration of mucin alterations associated with various diseases such as cancer.

  10. Giant lobelias exemplify convergent evolution

    PubMed Central

    2010-01-01

    Giant lobeliads on tropical mountains in East Africa and Hawaii have highly unusual, giant-rosette growth forms that appear to be convergent on each other and on those of several independently evolved groups of Asteraceae and other families. A recent phylogenetic analysis by Antonelli, based on sequencing the widest selection of lobeliads to date, raises doubts about this paradigmatic example of convergent evolution. Here I address the kinds of evidence needed to test for convergent evolution and argue that the analysis by Antonelli fails on four points. Antonelli's analysis makes several important contributions to our understanding of lobeliad evolution and geographic spread, but his claim regarding convergence appears to be invalid. Giant lobeliads in Hawaii and Africa represent paradigmatic examples of convergent evolution. PMID:20074322

  11. Atmospheres of Extrasolar Giant Planets

    NASA Astrophysics Data System (ADS)

    Marley, M. S.; Fortney, J.; Seager, S.; Barman, T.

    The key to understanding an extrasolar giant planet's spectrum - and hence its detectability and evolution - lies with its atmosphere. Now that direct observations of thermal emission from extrasolar giant planets (EGPs) are in hand, atmosphere models can be used to constrain atmospheric composition, thermal structure, and ultimately the formation and evolution of detected planets. We review the important physical processes that influence the atmospheric structure and evolution of EGPs and consider what has already been learned from the first generation of observations and modeling. We pay particular attention to the roles of cloud structure, metallicity, and atmospheric chemistry in affecting detectable properties through Spitzer Space Telescope observations of the transiting giant planets. Our review stresses the uncertainties that ultimately limit our ability to interpret EGP observations. Finally we will conclude with a look to the future as characterization of multiple individual planets in a single stellar system leads to the study of comparative planetary architectures.

  12. CMB lensing and giant rings

    SciTech Connect

    Rathaus, Ben; Itzhaki, Nissan E-mail: ben.rathaus@gmail.com

    2012-05-01

    We study the CMB lensing signature of a pre-inationary particle (PIP), assuming it is responsible for the giant rings anomaly that was found recently in the WMAP data. Simulating Planck-like data we find that generically the CMB lensing signal to noise ratio associated with such a PIP is quite small and it would be difficult to cross correlate the temperature giant rings with the CMB lensing signal. However, if the pre-inationary particle is also responsible for the bulk flow measured from the local large scale structure, which happens to point roughly at the same direction as the giant rings, then the CMB lensing signal to noise ratio is fairly significant.

  13. Structure of giant muscle proteins

    PubMed Central

    Meyer, Logan C.; Wright, Nathan T.

    2013-01-01

    Giant muscle proteins (e.g., titin, nebulin, and obscurin) play a seminal role in muscle elasticity, stretch response, and sarcomeric organization. Each giant protein consists of multiple tandem structural domains, usually arranged in a modular fashion spanning 500 kDa to 4 MDa. Although many of the domains are similar in structure, subtle differences create a unique function of each domain. Recent high and low resolution structural and dynamic studies now suggest more nuanced overall protein structures than previously realized. These findings show that atomic structure, interactions between tandem domains, and intrasarcomeric environment all influence the shape, motion, and therefore function of giant proteins. In this article we will review the current understanding of titin, obscurin, and nebulin structure, from the atomic level through the molecular level. PMID:24376425

  14. Progression of Pancreatic Adenocarcinoma Is Significantly Impeded with a Combination of Vaccine and COX-2 Inhibition1

    PubMed Central

    Mukherjee, Pinku; Basu, Gargi D.; Tinder, Teresa L.; Subramani, Durai B.; Bradley, Judy M.; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2013-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRASG12D mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E2 and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer. PMID:19109152

  15. In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells.

    PubMed

    Wang, Yuan-Chuen; Huang, Kai-Ming

    2013-03-01

    Infection with Helicobacter pylori causes extensive gastric epithelial cell inflammation which may progress to atrophic gastritis, intestinal metaplasia, and even gastric adenocarcinoma. Apigenin (4',5,7-trihydroxyflavone) is widely distributed in fruits and vegetables, and is a well-known antiinflammatory supplement with low cytotoxicity. In this study, we investigated the anti-inflammatory effects of apigenin in H. pylori-infected MKN45 cells, for which IκBα, cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), interleukin-8 (IL-8), IL-6, IL-1β, and mucin-2 (MUC-2) expressions were examined. Apigenin treatments (9.3-74 μM) significantly increased the IκBα expression, and thus inhibited nuclear factor kappa B (NF-κB) activation, and the inflammatory factor (COX-2, ICAM-1, ROS, IL-6, and IL-8) expressions decreased. The ROS levels decreased partially based on the intrinsic scavenging property of apigenin. In summary, apigenin treatments effectively inhibited NF-κB activation and the related inflammatory factor expressions, as well as increased MUC-2 expression in the H. pylori-infected MKN45 cells. The compound shows great potential as a candidate agent for the inhibition of H. pylori-induced extensive gastric epithelial cell inflammation.

  16. Role of GP82 in the selective binding to gastric mucin during oral infection with Trypanosoma cruzi.

    PubMed

    Staquicini, Daniela I; Martins, Rafael M; Macedo, Silene; Sasso, Gisela R S; Atayde, Vanessa D; Juliano, Maria A; Yoshida, Nobuko

    2010-03-02

    Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases. This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and subsequent systemic infection. Here we addressed that question by performing in vitro and in vivo experiments. A recombinant protein containing the complete gp82 sequence (J18), a construct lacking the gp82 central domain (J18*), and 20-mer synthetic peptides based on the gp82 central domain, were used for gastric mucin binding and HeLa cell invasion assays, or for in vivo experiments. Metacyclic trypomastigotes and J18 bound to gastric mucin whereas J18* failed to bind. Parasite or J18 binding to submaxillary mucin was negligible. HeLa cell invasion by metacyclic forms was not affected by gastric mucin but was inhibited in the presence of submaxillary mucin. Of peptides tested for inhibition of J18 binding to gastric mucin, the inhibitory peptide p7 markedly reduced parasite invasion of HeLa cells in the presence of gastric mucin. Peptide p7*, with the same composition as p7 but with a scrambled sequence, had no effect. Mice fed with peptide p7 before oral infection with metacyclic forms developed lower parasitemias than mice fed with peptide p7*. Our results indicate that selective binding of gp82 to gastric mucin may direct T. cruzi metacyclic trypomastigotes to stomach mucosal epithelium in oral infection.

  17. Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

    PubMed

    Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

    2016-06-15

    Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.

  18. Mucinous breast carcinomas lack PIK3CA and AKT1 mutations.

    PubMed

    Kehr, Elizabeth L; Jorns, Julie M; Ang, Daphne; Warrick, Andrea; Neff, Tanaya; Degnin, Michelle; Lewis, Rebecca; Beadling, Carol; Corless, Christopher L; Troxell, Megan L

    2012-12-01

    Activating point mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are among the most common molecular defects in invasive breast cancer. Point mutations in the downstream kinase AKT1 are seen in a minority of carcinomas. These mutations are found preferentially in estrogen receptor-positive and Her2-positive breast carcinomas; however, special morphologic types of breast cancer have not been well studied. Twenty-nine cases of pure invasive mucinous carcinoma and 9 cases of ductal carcinoma with mucinous differentiation were screened for a panel of point mutations (>321 mutations in 30 genes) using a multiplex polymerase chain reaction panel with mass spectroscopy readout. In addition, associated ductal carcinoma in situ, hyperplasia, or columnar cell lesions were separately tested where available (25 lesions). In 3 invasive cases and 15 ductal carcinoma in situ/proliferative lesions, PIK3CA hotspot mutations were, instead, tested by direct sequencing. No point mutations were identified in invasive mucinous breast carcinoma. This contrasts with the 35% frequency of PIK3CA mutations in a comparative group of invasive ductal carcinomas of no special type. Interestingly, PIK3CA hotspot point mutations were identified in associated ductal carcinoma in situ (3/14) and hyperplasia (atypical ductal hyperplasia [2/3], usual ductal hyperplasia [2/3], columnar cell change [1/5]), suggesting that PIK3CA mutations may play a role in breast epithelial proliferation. This series represents the largest study, to date, of PIK3CA genotyping in mucinous carcinoma and supports the unique pathogenetics of invasive mucinous breast carcinoma.

  19. Giant right atrial thrombi treated with thrombolysis.

    PubMed

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Ramos Cuadra, José Angel; Lara Toral, Juan; Lozano Cabezas, Cristobal; Fernández Guerrero, Juan Carlos

    2008-04-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery.

  20. Giant right atrial thrombi treated with thrombolysis

    PubMed Central

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Cuadra, José Ángel Ramos; Toral, Juan Lara; Cabezas, Cristobal Lozano; Guerrero, Juan Carlos Fernández

    2008-01-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery. PMID:18401474

  1. Cabergoline treatment in invasive giant prolactinoma.

    PubMed

    Alsubaie, Sadeem; Almalki, Mussa H

    2014-01-01

    Patients with invasive giant prolactinoma suffer from a constellation of symptoms including headache, blurred vision, lethargy, and sexual dysfunction. Cabergoline, a potent dopamine agonist, is a known medication prescribed for the treatment of invasive giant prolactinoma. Here, we report a case of invasive giant prolactinoma in a 52-year-old Saudi male with dramatic response to cabergoline treatment clinically, biochemically, and radiologically.

  2. Charting the Giants

    NASA Astrophysics Data System (ADS)

    2004-06-01

    zero expansion asymptotically after an infinite time and has a flat geometry). All three observational tests by means of supernovae (green), the cosmic microwave background (blue) and galaxy clusters converge at a Universe around Ωm ~ 0.3 and ΩΛ ~ 0.7. The dark red region for the galaxy cluster determination corresponds to 95% certainty (2-sigma statistical deviation) when assuming good knowledge of all other cosmological parameters, and the light red region assumes a minimum knowledge. For the supernovae and WMAP results, the inner and outer regions corespond to 68% (1-sigma) and 95% certainty, respectively. References: Schuecker et al. 2003, A&A, 398, 867 (REFLEX); Tonry et al. 2003, ApJ, 594, 1 (supernovae); Riess et al. 2004, ApJ, 607, 665 (supernovae) Galaxy clusters are far from being evenly distributed in the Universe. Instead, they tend to conglomerate into even larger structures, "super-clusters". Thus, from stars which gather in galaxies, galaxies which congregate in clusters and clusters tying together in super-clusters, the Universe shows structuring on all scales, from the smallest to the largest ones. This is a relict of the very early (formation) epoch of the Universe, the so-called "inflationary" period. At that time, only a minuscule fraction of one second after the Big Bang, the tiny density fluctuations were amplified and over the eons, they gave birth to the much larger structures. Because of the link between the first fluctuations and the giant structures now observed, the unique REFLEX catalogue - the largest of its kind - allows astronomers to put considerable constraints on the content of the Universe, and in particular on the amount of dark matter that is believed to pervade it. Rather interestingly, these constraints are totally independent from all other methods so far used to assert the existence of dark matter, such as the study of very distant supernovae (see e.g. ESO PR 21/98) or the analysis of the Cosmic Microwave background (e

  3. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  4. Metachronous Colon Metastases from Gastric Adenocarcinoma: A Case Report

    PubMed Central

    Pace, Ugo; Contino, Gianmarco; Chiappa, Antonio; Bertani, Emilio; Bianchi, Paolo P.; Fazio, Nicola; Renne, Giuseppe; Di Meglio, Giovanni; Andreoni, Bruno

    2009-01-01

    The colon is a very rare metastatic localization. Here we report a case of colonic metastases from gastric adenocarcinoma whose clinical presentation was suggestive of a de novo adenocarcinoma of the ascending colon. The authors discuss that in the presence of a previous history of gastric cancer, immunohistochemical analysis on endoscopic biopsies may help in the definition of a differential diagnosis. Furthermore, this rare metastatic localization might suggest a poor prognosis and a more accurate diagnostic work-up. PMID:20740169

  5. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    PubMed

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain

    2014-04-01

    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  6. Giant Serpentine Aneurysms: Multidisciplinary Management

    PubMed Central

    Anshun, W.; Feng, L.; Daming, W.

    2000-01-01

    Summary Sixty-five cases of intracranial giant serpentine aneurysms (GSΛs), including 61 cases reported in the literature and four additional cases presented in this study were reviewed. The clinical presentation, possible causes, natural history, and especially management of GSAs are discussed with emphasis on the need for aggressive intervention and multidisciplinary management. PMID:20667180

  7. On the Shoulders of Giants...

    DTIC Science & Technology

    2013-01-01

    REFERENCES 1. Newton I. Turnbull HW, ed. Correspondence of Isaac Newton . Vol I: 1661Y1675. Cambridge, United Kingdom: Cambridge University Press; 1959:416...calendar), Sir Isaac Newtonopined to Robert Hooke, ‘‘If I have seen further [than you and Descartes], it is by standing on the shoulders of giants.’’1 That

  8. The giant panda gut microbiome.

    PubMed

    Wei, Fuwen; Wang, Xiao; Wu, Qi

    2015-08-01

    Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed.

  9. Nursery of Giants

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Hidden behind a shroud of dust in the constellation Cygnus is a stellar nursery called DR21, which is giving birth to some of the most massive stars in our galaxy. Visible light images reveal no trace of this interstellar cauldron because of heavy dust obscuration. In fact, visible light is attenuated in DR21 by a factor of more than 10,000,000,000,000,000,000,000,000,000,000,000,000,000 (ten thousand trillion heptillion).

    New images from NASA's Spitzer Space Telescope allow us to peek behind the cosmic veil and pinpoint one of the most massive natal stars yet seen in our Milky Way galaxy. The never-before-seen star is 100,000 times as bright as the Sun. Also revealed for the first time is a powerful outflow of hot gas emanating from this star and bursting through a giant molecular cloud.

    This image is a large-scale mosaic assembled from individual photographs obtained with the InfraRed Array Camera (IRAC) aboard Spitzer. The image covers an area about two times that of a full moon. The mosaic is a composite of images obtained at mid-infrared wavelengths of 3.6 microns (blue), 4.5 microns (green), 5.8 microns (orange) and 8 microns (red). The brightest infrared cloud near the top center corresponds to DR21, which presumably contains a cluster of newly forming stars at a distance of 10,000 light-years.

    Protruding out from DR21 toward the bottom left of the image is a gaseous outflow (green), containing both carbon monoxide and molecular hydrogen. Data from the Spitzer spectrograph, which breaks light into its constituent individual wavelengths, indicate the presence of hot steam formed as the outflow heats the surrounding molecular gas. Outflows are physical signatures of processes that create supersonic beams, or jets, of gas. They are usually accompanied by discs of material around the new star, which likely contain the materials from which future planetary systems are formed. Additional newborn stars, depicted in green, can be seen surrounding the

  10. Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.

    PubMed

    Park, Won Young; Kim, Mi Hyun; Shin, Dong Hoon; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Park, Do Youn; Lee, Chang Hun; Sol, Mee Young

    2012-09-01

    Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.

  11. BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS

    PubMed Central

    Skoog, Emma C.; Padra, Médea; Åberg, Anna; Gideonsson, Pär; Obi, Ikenna; Quintana-Hayashi, Macarena P.; Arnqvist, Anna; Lindén, Sara K.

    2017-01-01

    Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have. Binding of H. pylori to Leb-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Leb. Furthermore, deletion of arsS lead to a decrease in binding to Leb-glycoconjugates and Leb-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Leb-glycoconjugates. Inhibition of proliferation caused by adhesin dependent binding to mucins, and the subsequent aggregation suggests a new role of mucins in the host defense against H. pylori. This aggregating trait of mucins may be useful to incorporate into the design of adhesin inhibitors and other disease intervention molecules. PMID:28106125

  12. Hierarchical Assembly of Model Cell Surfaces: Synthesis of Mucin Mimetic Polymers and their Display on Supported Bilayers

    PubMed Central

    Rabuka, David; Parthasarathy, Raghuveer; Lee, Goo Soo; Chen, Xing; Groves, Jay T.; Bertozzi, Carolyn R.

    2008-01-01

    Molecular level analysis of cell surface phenomena could benefit from model systems comprising structurally-defined components. Here we present the first step toward bottom-up assembly of model cell surfaces – the synthesis of mucin mimetics and their incorporation into artificial membranes. Natural mucins are densely glycosylated O-linked glycoproteins that serve numerous functions on cell surfaces. Their large size and extensive glycosylation makes the synthesis of these biopolymers impractical. We designed synthetically tractable glycosylated polymers that possess rod-like extended conformations similar to natural mucins. The glycosylated polymers were end-functionalized with lipid groups and embedded into supported lipid bilayers where they interact with protein receptors in a structure-dependent manner. Furthermore, their dynamic behavior in synthetic membranes mirrored that of natural biomolecules. This system provides a unique framework with which to study the behavior of mucin-like macromolecules in a controlled, cell surface-mimetic environment. PMID:17425309

  13. Hepatoid adenocarcinoma of the stomach – a different histology for not so different gastric adenocarcinoma: a case report

    PubMed Central

    Gálvez-Muñoz, Elisa; Gallego-Plazas, Javier; Gonzalez-Orozco, Verónica; Menarguez-Pina, Francisco; Ruiz-Maciá, José A; Morcillo, Miguel A

    2009-01-01

    Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describi