Sample records for human gallbladder carcinoma


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    Blaž Trotovšek


    Full Text Available Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times in women and in people over 50 years old (90%. According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most important risk factors for development of gallbladder carcinoma are: bile stones, chronic inflammation and polyps of the gallbladder. Carcinoma of the gallbladder develops in only 2–3% of the patients with bile stones. When discovered, carcinoma has already invaded the liver in 60%, regional lymph nodes in 45% and the other surrounding organs in 40%. Carcinoma is at time of diagnosis already disseminated in distant organs in 20%. Only in 10% of the patients it is confined to the gallbladder wall. Before the routine use of the ultrasound, computed tomography and tumour markers the disease was discovered preoperatively in 10% versus 90% today. Diagnostic percutaneous biopsy is not recommended. TNM classification and staging of the disease is important for the decision of the modality of treatment.Conclusions. For TNM stage I gallbladder carcinoma, simple cholecystectomy is sufficient. When stage II-IVa is discovered, »en block« resection of gallbladder, liver segments 4b and 5, common bile duct and thorough lymphadenectomy is recommended. Regional radiotherapy and intraarterial chemotherapy with Mitomycin-C are showing promising results. Longterm outcome in patients with gallbladder carcinoma is improving but it is still disappointing.

  2. Gallbladder carcinoma in Jordan. (United States)

    Al-Qudah, Mohammad S; Daradkeh, S; Sroujieh, Ahmad S; Farah, Ghassan R; Masaad, Jamal


    Despite advances in diagnostic and therapeutic modalities, the prognosis of gallbladder carcinoma is still poor. The purpose of this study is to look for peculiarities of primary gallbladder carcinoma in Jordan regarding its incidence, clinical and pathological aspects. A retrospective study over a period of 19 years comprising 66 patients was reviewed; only patients treated primarily in our hospital were included. There were 40 females and 26 males (ratio of 3:2). The main presenting symptom was abdominal pain in 54 patients (82%); correct preoperative diagnosis was made in only 20% of cases. Cholecystectomy alone was the most commonly performed operation (32 cases), cholecystectomy in combination with biliary bypass and/or hepatic resection (16 cases), biopsy of the gallbladder was performed in 12 cases and bypass with T-tube drainage in 6 cases. Postoperative morbidity and mortality were encountered in 48% and 18% respectively. The incidence and clinicopathological aspects of gallbladder cancer in Jordan seem to resemble that in the west, albeit with a lower age incidence. Diagnosis remains difficult and the outcome is still poor in the majority of cases.

  3. [Primary carcinoma of the gallbladder]. (United States)

    Ghilardi, G; Bortolani, E M; Sgroi, G; Pecis, C


    Primary carcinoma of the gallbladder, while infrequent, is the most representative among the malignant neoplasms of the biliary tract. The diagnosis of carcinoma of the gallbladder was made in 22 out of 1252 operations performed for gallbladder disease (1.8%) since January 1980 through June 1988: only in 9% of the subjects a malignant tumor of the gallbladder was suspected preoperatively. In 21 cases the carcinoma was associated with chronic lithiasic cholecystitis. The 22 cases were assessed according to the classification proposed by Nevin. The operations performed were: 4 routine cholecystectomies (stages I and II) 4 cholecystectomies with lymphadenectomy (stages I and II); 4 cholecystectomies with lymphadenectomy and liver wedge resection of the bed of the gallbladder (stages II, III, IV, V); 7 explorative laparotomies and 3 gastrojejunal anastomoses (stage V). A complete follow-up was available for each of the 22 subjects: cumulative survival rates were calculated according to Kaplan-Meyer. The overall 5-year cumulative survival rate after operation was 19% for the whole group, whereas it reached 76% for the subgroup of 9 patients classified in stages I and II. This analysis reinforces the statement that surgical therapy can achieve excellent results if brought about before cancer overwhelms the muscular layer of the gallbladder wall. Thus, as the preoperative diagnosis of gallbladder carcinoma is extremely difficult and uncertain, any delay in performing cholecystectomy seems to be unwise in all those cases of chronic benign disease of the gallbladder (whether lithiasic in nature or not) that are suspected to be a major risk factor for cancer degeneration because of their frequent association with the carcinoma of the gallbladder.

  4. Incidental gallbladder carcinoma: our experience. (United States)

    Panebianco, A; Volpi, A; Lozito, C; Prestera, A; Ialongo, P; Palasciano, N


    Aim. Gallbladder carcinoma is an uncommon cancer with a poor prognosis. In the era of laparoscopic cholecistectomy for treatment of benign diseases incidental gallbladder carcinoma has dramatically increased and now constitutes the major way patients present with gallbladder cancer and allows to detect cancer at early stages with a better prognosis. In this single-center study we report our experience with gallbladder carcinoma incidentally diagnosed during or after laparoscopic colecistectomy performed for cholelithiasis. Methods. From January 2003 to December 2011 a total of 1193 patients underwent cholecistectomy at General Surgical Unit III of University of Bari. The patients were 458 males and 735 females, mean age was 52 years (range 19-91). In 6 of 1188 patients adenocarcinoma was present in the pathologic specimens (0,5%). Results. Of 1188 patients in whom laparoscopic cholecistectomy was attempted adenocarcinoma was diagnosed histopathologically in 6 cases (0,5%). There was no suspicion of malignancy to any of them. Intraoperatively, gallbladder wall appeared abnormal in one patients and frozen section analysis revealed adenocarcinoma. In the remaining 5 cases routine histopathological studies revealed the diagnosis of gallbladder carcinoma. One patient had T1 tumor, two had T2 and three had T3 tumor. Conclusions. In the present study the rate of incidental gallbladder carcinoma was 0,5%, according to the published English language literature. The risk factors widely related to the gallbladder cancer are advanced age and gallstones disease. The therapeutic approach to gallbladder cancer was applied according to the stage of tumor, but in our study this was possible only in two patients with T2 and T3 tumor since high risk and important comorbidities were the main causes for the refusal of 3 patient out of 5. Only the T1 patient underwent simple cholecystectomy. Similar to other reports in this single-center study the diagnosis of incidental gallbladder

  5. Realtime ultrasonographic findings in gallbladder carcinoma

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    Ko, Y. T.; Woo, S. K.; Suh, I. J.; Lim, J. H.; Kim, H. K.; Kim, S. Y.; Ahn, C. Y. [Kyung Hee University Hospital, Seoul (Korea, Republic of)


    It is well known that realtime ultrasonography is the primary diagnostic modality to evaluate gallbladder diseases. The authors studied ultrasonographic findings of 10 pathologically proven gallbladder carcinoma patients, and it was compared with the findings of 4 cases of ERCP and 2 cases of CT which were performed at the same period. The results were as follows: 1. They were 6 males and 4 females with over 50 years of age except a 41 year old female. 2. The ultrasonographic classifications of the cases were 4 of fungating mass types, 3 of mass filling gallbladder types, 2 wall thickening types and 1 of mixed type, wall thickening and fungating mass. 3. Seven cases of cholecystitis, 6 cases of intrahepatic biliary duct dilatation, 5 cases of gallstone, 4 cases of common bile duct dilatation, 4 cases of sludge bile, 2 cases of gallbladder dilatation, 1 case of right sub phrenic and pericholecystic abscess due to perforated gallbladder. 4. Five cases of mesenteric infiltrations, 3 cases of hepatic infiltration adjacent to gallbladder, 2 cases of lymphatic metastasis to right lobe of liver and 2 cases of pericholedochal and pericaval lymph node metastasis. 5. The indistinct margin between gallbladder and surrounding organ adjacent to gallbladder mass or gallbladder wall thickening suggest cancer infiltration to adjacent organ such as liver or omentum. 6. If gallstone is engulfed in thickened gallbladder wall, the wall thickening suggests gallbladder carcinoma. 7. The differentiation between fungating mass and sludge bile, and the determination of mass could be done by positional change. 8. The preoperative ultrasonic diagnositc accuracy was in 9 out of 10 cases (90%). 9. Because of the frequent cystic duct obstruction by associated inflammation, the diagnostic accuracy of ERCP for gallbladder carcinoma was low.

  6. [Gallbladder carcinoma in Iceland 2004-2013]. (United States)

    Baldvinsdottir, Bryndis; Hauksson, Haraldur; Haraldsdóttir, Kristin Huld


    Gallbladder carcinoma is about 0.5% of all cancer. The outcome of patients with gallbladder carcinoma is overall bad and the only potentially curative treatment is surgery. The aim of this study was to determine the disease's prevalence in Iceland and outcome of the patients diagnosed in the study period. This was a retrospective study of all diagnosed patients with gallbladder carcinoma during the years 2004-2013. A list of patients was obtained from the Icelandic Cancer Registry. Information was gathered from the patient's charts in Landspitali University Hospital and the Hospital in Akureyri. Descriptive statistics was used to analyze the results. Median follow-up time was 6 years. Twenty-four patients were diagnosed with gallbladder carci-noma in Iceland during the study period, 16 women and 8 men. Eighteen patients were diagnosed in Landspitali and six in the Hospital in Akureyri. The average age at diagnosis was 73 years. Eighteen patients have died, on average 5 months after the time of diagnosis. Adenocarcinoma was the most common cancer type (n=19). Three patients (3/24, 12.5%) underwent extended operation following the diagnosis of the gallbladder carcinoma. Nine patients (9/24, 37.5%) had advanced disease at the time of diagnosis and died within two months after being diagnosed with gallbladder carcinoma. Gallbladder carcinoma is a rare cancer type in Iceland and has a bad prognosis. One third of the patients had no connection with Landspitali University Hospital following the diagnosis. Extended surgery following the diagnosis was seldom performed. Key words: gallbladder carcinoma, gastrointestinal cancer, adenocarcinoma, extended cholecystectomy. Correspondence: Kristin Huld Haraldsdottir,

  7. Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma

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    Giang Tran H


    Full Text Available Abstract Background Carcinoma of the gallbladder (GBC clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC. Methods We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5 with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC. Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract. Results These cases illustrate seven potential pitfalls which can be encountered. These include: 1 mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis, 2 misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis, 3 differentiating between primary NEC of gallbladder and metastasis, 4 confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5 confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6 undersampling early, grossly occult disease, and 7 misinterpreting extracellular mucin pools. Conclusions Clinical history and a high index of suspicion are

  8. Leptomeningeal carcinomatosis in a patient with gallbladder carcinoma

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    Nisha Jose


    Full Text Available Carcinomatous meningitis is a rare manifestation of malignancy. It is increasingly being recognized in lung carcinoma, breast carcinoma, melanomas, gastrointestinal malignancies, lymphomas, and leukemia and it is almost never seen in gallbladder malignancies. We present a case whose primary presentation was as a carcinomatous meningitis that was subsequently found to be secondary to a gallbladder primary.

  9. Gallbladder carcinoma: role of radiation therapy

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    Houry, S.; Schlienger, M.; Huguier, M.; Lacaine, F.; Penne, F.; Laugier, A. (Hopital Tenon, 75 - Paris (France))


    Since 1977 we have treated 20 patients with gallbladder carcinoma with postoperative radiotherapy. In four patients all the tumour was resected with the intent of cure. In 12 patients, the lesion was partially resected and in four patients no resection was performed. Seven patients in whom the tumour was partially resected or not resected also had chemotherapy. Our evaluation was retrospective and we compared our results with historical control groups comparable with respect to surgical procedures and pathological staging. In patients operated on for cure, one patient is alive at 84 months, the others died at 7, 8 and 33 months. In patients in whom the tumour was partially resected the mean survival time was 8.1 months and two patients are still alIve 7.0 months after treatment. According to the Nevin classification the mean survival time in stage IV and V patients was respectively 9.2 and 7.2 months. There was no difference in survival between patients treated or not treated with chemotherapy. This experience is the largest published and suggests that radiotherapy may increase survival after no resection or palliative resection of gallbladder carcinoma. (author).

  10. A Case Report of Squamous Cell Carcinoma of Gallbladder

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    A. Dehghan


    Full Text Available Introduction : Epithelial cell carcinoma is the most common malignant neoplasm of gallbladder , but squamous cell carcinoma (SCC is rare.Case Report: Following the diagnosis of hydropsy of gallbladder in a sonography of a 60 years-old woman, cholesistectomy was performed. On macroscopic pathological examination, brownish deformed gallbladder was seen. After opening, on mucosal surface there was a cream, elastic polypoid tumoral lesion (2×1×0.5 cm. On microscopic evaluation, a pattern of pure and differentiated invasive Squamous Cell Carcinoma was diagnosed. Conclusion: During the last twenty-two years, this has been the first report of SCC of gallbladder from province of Hamadan with incidence of 2.8% in Iran. This case can be used in hystogenesis of SCC of gallbladder.

  11. Characterization of cancer stem-like cells derived from a side population of a human gallbladder carcinoma cell line, SGC-996. (United States)

    Li, Xin-xing; Wang, Jian; Wang, Hao-lu; Wang, Wei; Yin, Xiao-bin; Li, Qi-wei; Chen, Yu-ying; Yi, Jing


    The cancer stem cell (CSC) hypothesis proposes that CSCs, which can renew themselves proliferate infinitely, and escape chemotherapy, become the root of recurrence and metastasis. Previous studies have verified that side population (SP) cells, characterized by their ability to efflux lipophilic substrate Hoechst 33342, to share many characteristics of CSCs in multiplying solid tumors. The purpose of this study was to sort SP cells from a human gallbladder carcinoma cell line, SGC-996 and to preliminarily identify the biological characteristics of SP cells from the cell line. Using flow cytometry we effectively sorted SP cells from the cell line SGC-996. SP cells not only displayed higher proliferative, stronger clonal-generating, more migratory and more invasive capacities, but showed stronger resistance. Furthermore, our experiments demonstrated that SP cells were more tumorigenic than non-SP counterparts in vivo. Real-time PCR analysis and immunocytochemistry showed that the expression of ATP-binding cassette subfamily G member 2 (ABCG2) was significantly higher in SP cells. Hence, these results collectively suggest that SP cells are progenitor/stem-like cells and ABCG2 might be a candidate marker for SP cells in human gallbladder cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. The role of the gallbladder in humans

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    J.L. Turumin


    Full Text Available The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid, thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the “gastric chyme” moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans.

  13. The role of the gallbladder in humans. (United States)

    Turumin, J L; Shanturov, V A; Turumina, H E


    The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the "gastric chyme" moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  14. Ovarian metastasis of primary biliary and gallbladder carcinomas. (United States)

    Ayhan, A; Guney, I; Saygan-Karamursel, B; Taskiran, C


    The ovary is a frequent site of metastasis from a wide variety of malignant neoplasias, with the majority originating in the GI tract. The best known tumor of this type is signet ring cell adenocarcinoma (Krukenberg tumor). The gallbladder and bile ducts are rare sources of these metastases. We are reporting two such cases in which the patients presented with no hepatic symptoms and vague gastrointestinal complaints. The gallbladder and bile duct carcinomas were incidental findings during exploratory laparatomy for an ovarian mass.

  15. Expression of the RIP-1 Gene and its Role in Growth and Invasion of Human Gallbladder Carcinoma

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    Guangwei Zhu


    Full Text Available Background and Aim: Receptor interacting protein(RIP-1 is thought to have a significant role in inflammation signaling pathways; however, the role of RIP-1 in malignant tumors is largely unknown. Methods: The present study examined the functions and underlying mechanisms of RIP-1 in gallbladder cancer in vitro and in vivo. In this study we determined the expression and role of RIP-1 in 60 clinical specimens from patients with gallbladder cancer and 3 gallbladder cancer cell lines. Using siRNA targeting RIP-1, plasmid vectors (phU6-EGFP-puro/siRIP-1 were constructed and transfected into the gallbladder cells to characterize the biological effect of RIP-1. Results: In vitro experiments indicated that silencing of RIP-1 in NOZ cells significantly suppressed growth and invasion. Furthermore, silencing of RIP-1 affected the RIP1-NF-κB/c-jun(AP-1-VEGF-C pathways in NOZ cells. Silencing of RIP-1 in vivo inhibited tumor growth in a NOZ cell subcutaneous xenograft model. Immunohistochemstry analysis of the tumor in thesubcutaneous xenograft model also suggested that RIP-1 mediates the expression of VEGF-C. Conclusion: We have elucidated therelationship between RIP-1 overexpression and the growth and invasion of gallbladder cancer from clinical specimens using a xenograft model. We provide evidence that a reduction in the expression of RIP-1 in gallbladder cancer cells can exert inhibitory effects on the ability of cells to grow and invade in vitro. Thus, targeting RIP-1may be useful in the treatment of gallbladder cancer.

  16. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

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    Paolo Aiello


    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  17. Gallbladder metastases from ductal papillary carcinoma of the breast. (United States)

    Murguia, Eduardo; Quiroga, Daniel; Canteros, Geraldine; Sanmartino, Cesar; Barreiro, Mariano; Herrera, Jose


    Breast cancer occurs primarily in women aged 25 years or older. Breast carcinoma has the potential for widespread dissemination, such as metastasis to axillary lymph nodes, bone, lung, pleura, brain, and soft tissues. Liver, gastrointestinal, and biliary tract involvement are infrequent. We report a patient, a 62-year-old woman, with symptomatic cholelithiasis. The patient proceeded to laparoscopic cholecystectomy. She had a previous history of mastectomy with axillary lymphadenectomy, performed for a breast ductal papillary carcinoma, 10 years prior to the cholecystectomy. The gallbladder was hydropic; the wall was thickened, with a focal broad-based lesion on the mesenteric face of the body. Histopathological evaluation of the focal broad-based lesion of the gallbladder revealed poorly differentiated adenocarcinoma infiltration, without mucosal involvement. Subsequent immunohistochemical examination showed the lesion to be cytokeratin 7(CK7)-positive and cytokeratin 20 (CK20)-negative. Estrogen receptor (ER) and progesterone receptor (PgR) were positive. The final pathological diagnosis was breast ductal papillary carcinoma metastases to the gallbladder. Mammography of the other breast was normal. Computed tomography (CT) scan of the brain, chest, abdomen, and pelvis was performed, without any pathological findings. Bone Tc-99 scintigraphy was normal. Six months after the surgery positron emission tomography (PET) showed no evidence of metastatic disease. Two years after the surgery, the patient died, in the absence of recurrence. A literature review revealed only a few more cases of metastasic breast carcinoma to the gallbladder.

  18. Human gallbladder pressure and volume

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    Borly, L; Højgaard, L; Grønvall, S


    Increased gallbladder (GB) pressure is probably a part of the pathogenesis of acute cholecystitis, and measurements of GB pressure might therefore be of interest. The aim of this study was to validate a microtip pressure transducer for intraluminal GB pressure measurements. In vitro precision and...

  19. Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma cells


    Weng, Hao; Tan, Zhu-Jun; Hu, Yun-Ping; Shu, Yi-Jun; Bao, Run-Fa; Jiang, Lin; Wu, Xiang-Song; Li, Mao-Lan; Ding, Qian; Wang, Xu-An; Xiang, Shan-Shan; Li, Huai-Feng; Cao, Yang; Tao, Feng; Liu, Ying-Bin


    Background Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro. Methods The anti-tumor activity of UA against GBC-SD and SGC-996 cells was assessed using MTT and col...

  20. Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions

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    Parwani, Anil V.; Geradts, Joseph; Caspers, Eric; Offerhaus, G. Johan; Yeo, Charles J.; Cameron, John L.; Klimstra, David S.; Maitra, Anirban; Hruban, Ralph H.; Argani, Pedram


    Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing hi neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6

  1. Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines. (United States)

    Wang, Shihang; Liu, Chao; Liu, Xinjiang; He, Yanxin; Shen, Dongfang; Luo, Qiankun; Dong, Yuxi; Dong, Haifeng; Pang, Zhigang


    Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

  2. Carcinoma of the gallbladder. The Roswell Park experience. (United States)

    Silk, Y N; Douglass, H O; Nava, H R; Driscoll, D L; Tartarian, G


    The median survival, from diagnosis, of patients with cancer of the gallbladder is 6 months. Our purpose in reviewing our experience was to identify factors, either in patient characteristics or treatment, that influence this statistic. In 22 years 71 cases of gallbladder carcinoma were referred to Roswell Park Memorial Institute in Buffalo, New York. Most had a cholecystectomy that revealed an unsuspected neoplasm, before referral. Mean age was 62 years and 75% were female. Symptoms, signs, and laboratory and imaging studies were uniformly unhelpful in determining the diagnosis. Early diagnosis at a stage amenable to surgical excision remains the sole salvation. Patients who receive chemotherapy did better than those who did not, but this is probably a reflection of patient selection. Newer treatment modalities are urgently needed.

  3. Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma

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    Bardeesy Nabeel


    Full Text Available Abstract Background The genetics of advanced biliary tract cancers (BTC, which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%. KRAS mutations were identified in 3 (13% intra-hepatic cholangiocarcinomas and 1 (33% perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.

  4. MiR-138 Suppresses Cell Proliferation by Targeting Bag-1 in Gallbladder Carcinoma (United States)

    Gong, Wei; Weng, Mingzhe; Quan, Zhiwei


    Background MiR-138 is frequently downregulated in different cancer types and is thought to be involved in the progression of tumorigenesis. However, the molecular mechanism of miR-138 involvement in gallbladder carcinoma still remains unknown. Methods The expression of miR-138 in 49 gallbladder carcinoma samples and paired normal gallbladder samples was analyzed using quantitative reverse transcription–polymerase chain reaction. The biological functions of miR-138 and Bag-1 (Bcl-2-associated athanogene-1) on cell proliferation were examined using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and apoptosis assays. Targets of miR-138 were predicted using bioinformatics and validated using luciferase reporter and Western blot analyses. The in vivo effects of miR-138 were examined using subcutaneous inoculation of gallbladder carcinoma cells in Balb/c nude mice. Results Compared with their paired normal gallbladder samples, the gallbladder carcinoma samples had decreased expression of miR-138 and increased expression of Bag-1. Overexpression of miR-138 inhibited the proliferation of gallbladder carcinoma cells. Bag-1 was defined as a novel target of miR-138. Both the inhibition of Bag-1 by miR-138 and the silencing of Bag-1 by siRNA led to alterations of apoptosis-related proteins such as Bcl-2 and Bax. Restoring expression of Bag-1 eliminates the effects of miR-138 on cell proliferation and apoptosis. Furthermore, overexpression of miR-138 markedly inhibited the growth of tumors in the gallbladder carcinoma xenograft model in nude mice. Conclusions Expression of miR-138 is frequently reduced in gallbladder carcinoma when compared to normal cells. Overexpression of miR-138 inhibited cell proliferation by directly suppressing the expression of Bag-1. These results suggest that miR-138 plays an important role in inhibiting the growth of gallbladder carcinoma. PMID:25962180

  5. A clinicopathological study of nine cases of gallbladder carcinoma in 1122 cholecystectomies in Johor, Malaysia. (United States)

    Khoo, Joon Joon; Nurul, Akmar Misron


    An audit of 1122 cholecystectomies for a 6-year period from 2000 to 2005 was done to review cases of primary carcinoma of gallbladder. There were nine cases of primary carcinoma of gallbladder. Six were females and 3 males. Their ages ranged from 27 to 81 years. Pre-operatively, only 2 (11.1%) were clinically suspected of carcinoma while 3 were diagnosed as cholecystitis, two as cholelithiasis and one case each of ovarian cyst and intestinal obstruction. Intra-operatively, an additional four cases were suspected as gallbladder carcinoma with the remaining three cases diagnosed as only having gallstones. Altogether only 5 (55.6%) cases were associated with gallstones. Six (66.67%) cases of gallbladder carcinoma had abnormal macroscopical lesions noted; either papillary lesions or polypoid masses. The remaining 3 cases had thickening of the wall, consistent with chronic cholecystitis. Seven cases were found histologically to be adenocarcinoma. Of these, two were papillary carcinoma and one signet ring cell type adenocarcinoma. One case of squamous cell carcinoma and one case of adenosquamous carcinoma were noted. This study highlights the importance of careful macroscopical and microscopical evaluation of a routine pathological examination of gallbladder removed for cholecystitis or cholelithiasis. It provides the incidence of gallbladder carcinoma in patients who underwent cholecystectomies in a government hospital in Johor, Malaysia.

  6. Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells

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    Xu-An Wang


    Full Text Available Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8 and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells. Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI double-staining assay, and the mitochondrial membrane potential (ΔΨm decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

  7. Biliary Dyskinesia as a Rare Presentation of Metastatic Breast Carcinoma of the Gallbladder: A Case Report

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    A. Markelov


    Full Text Available Background. Breast carcinoma is the most common malignancy in women worldwide. It is most commonly associated with metastases to the liver, lung, bone, and the brain. Invasive lobular carcinoma is a less common pathology with slightly higher metastases to the upper gastrointestinal tract. Invasive lobular carcinoma metastasis to the gallbladder is extremely rare. Method. In this paper we are presenting a case of a 67-year-old female with metastases of invasive lobular breast cancer to the gallbladder six years after her therapy. Conclusion. This case clearly signifies the nature of the micrometastatic foci of the invasive lobular carcinoma even many years after a successful treatment.

  8. Mechanism of resveratrol-induced relaxation in the human gallbladder. (United States)

    Tsai, Ching-Chung; Lee, Ming-Che; Tey, Shu-Leei; Liu, Ching-Wen; Huang, Shih-Che


    Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips. We studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker). The present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways. This study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of biliary

  9. A gallbladder tumor revealing metastatic clear cell renal carcinoma: report of case and review of literature

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    Ghaouti Merieme


    Full Text Available Abstract Metastatic renal cell carcinoma in the gallbladder is extremely rare, with reported frequencies of less than 0.6% in large autopsy reviews. Only 40 cases were reported in the literature. We report a first case of gallbladder polypoid tumor revealing metastatic clear cell renal cell carcinoma, which demonstrates the importance of radiological tests, histology and immunohistochemistry when making a definitive diagnosis. These examinations also allow differentiating metastatic clear cell renal cell carcinoma from other polypoid lesions in the gallbladder with clear cell morphology. Cholecystectomy should be performed to obtain a definitive diagnosis and to improve survival in case of solitary metastatic renal cell carcinoma. Virtual slides The virtual slides’ for this article can be found here:

  10. Measurement of the mechanical properties of the human gallbladder. (United States)

    Karimi, Alireza; Shojaei, Ahmad; Tehrani, Pedram


    Gallbladder is a small organ of the body which is located in the right side of the liver. It is responsible of storing the bile and releasing it to the intestine. The gallbladder can subject to the mechanical deformation/loading as a result of the cholecystitis, cholesterolosis of the gallbladder, etc. However, so far the mechanical properties of the human gallbladder have not been measured. This study was aimed at conducting an experimental study to measure the mechanical properties of the human gallbladder under the axial and transversal tensile loadings. To do that, the gallbladder tissue of 16 male individuals was excised during the autopsy and subjected to a series of axial and transversal loadings under the strain rate of 5 mm/min. The amount of elastic modulus as well as the maximum/failure stress of the tissues were calculated via the resulted stress-strain diagrams and reported. The results revealed that the axial and transversal elastic modulus were 641.20 ± 28.12 (mean ± SD) and 255 ± 24.55 kPa, respectively. The amount of maximum stresses was also 1240 ± 99.94 and 348 ± 66.75 kPa under the axial and transversal loadings, respectively. The results revealed a significantly higher axial stiffness (p mechanical properties of the human gallbladder tissue, but also for providing a diagnosis tool for the doctors to have a suitable threshold value of the healthy gallbladder tissue.

  11. Primary Pure Squamous Cell Carcinoma of Gallbladder Presenting as Acute Cholecystitis

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    Massood Hosseinzadeh


    Full Text Available Squamous cell carcinoma of the gallbladder is rare and constitutes only 0.5-3% of all malignancies of this organ. Most of the reported cases have had a component of adenocarcinoma. We report a 70-year-old man who presented with acute onset right upper quadrant pain. He operated on based on a presumptive diagnosis of acute cholecystitis according to clinical and ultrasonographic findings. Histopathological examination of the infiltrating mass of the gallbladder revealed well differentiated keratinized squamous cell carcinoma invading full wall thickness. Thorough evaluations revealed no other primary site for the tumor. Pure primary squamous cell carcinoma of the gallbladder is rarely reported. Clinicians and pathologists must be aware of its vague clinical presentations.

  12. Laparoscopic Cholecystectomy: Incidental Carcinoma of the Gallbladder with Abdominal Wall and Axillary Node Metastasis

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    Richard C. Johnson


    Full Text Available A case report is presented of intra-mural gallbladder carcinoma discovered incidentally after laparoscopic cholecystectomy who subsequently developed abdominal wall recurrence at the epigastric exit port, and axillary lymph node metastases. Possible preventative steps for tumour dissemination and a management plan if incidental carcinoma is diagnosed is discussed. The use of a non-porous retrieval bag, early recognition of the carcinoma and excision of the exit wound are advocated.

  13. [Etiopathogenic hypothesis on carcinoma of the gallbladder: our study]. (United States)

    Rizzo, A G; Barbuscia, M; Sanò, M; Cancellieri, A; Nicotina, P; Stassi, G; Lemma, G; Lemma, F


    The authors are interested in determining causes of gallbladder cancer (GBC). By this intention, they theorize a correlation between genetic modifications (which are responsible of malignant transformation of biliary epithelium) and some intestinal infections. From 1999 to 2004 they observed 15 GBC and all 15 gallbladder have been analyzed histologically and from microbiological aspect; by these means from 1999 till 2004 they have studied also 30 persons with colelithiasis. The authors noticed that bile of both groups contained, in three cases in the first and in 8 cases in the second, a germ named Escherichia Coli which normally lives in intestine, while in 10 operated gallbladders of the first group and 12 of the second there was a positive for k-ras. They are studying to confirm their theories.

  14. Ovarian metastasis following gallbladder carcinoma: a case report. (United States)

    Carlomagno, C; Insabato, L; Bifulco, G; De Placido, S; Lauria, R


    Mucinous ovarian cancer raises problems of differential diagnoses because it is often difficult to distinguish the primary from the metastatic form. Most metastatic ovarian tumors originate from the gastrointestinal tract, mainly colorectal, gastric, pancreatic; the gallbladder is a very rare source of ovarian metastases. We report a case of ovarian metastases from a gallbladder cancer, incidentally diagnosed more than 2.5 years earlier during a laparoscopic intervention for biliary lithiasis. The interest of this case lies in the long progression-free survival, the venous thromboembolism syndrome that preceded by a few months the diagnosis of the ovarian mass and the discrepancy between the radiologic and the laparoscopic stage assessment.

  15. A case report of the clear cell variant of gallbladder carcinoma

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    Ravi Maharaj


    Conclusion: In these cases, clinical case management should be personalized for increased survival with the possible incorporation of next generation sequencing approaches to guide therapeutic algorithms. We discuss this exceedingly rare case of the clear cell variant of gallbladder carcinoma in detail, highlighting some of the diagnostic, and clinical challenges.

  16. Combined extrahepatic bile duct resection for locally advanced gallbladder carcinoma: does it work? (United States)

    Igami, Tsuyoshi; Ebata, Tomoki; Yokoyama, Yukihiro; Sugawara, Gen; Mizuno, Takashi; Yamaguchi, Junpei; Shimoyama, Yoshie; Nagino, Masato


    Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion.

  17. Carcinoma involving the gallbladder in elderly patients presenting with acute cholecystitis. (United States)

    Liu, K J; Richter, H M; Cho, M J; Jarad, J; Nadimpalli, V; Donahue, P E


    The unexpected intraoperative finding of a cancerous gallbladder has become particularly problematic, because cancer recurs rapidly after laparoscopic cholecystectomy. It would be desirable to identify the patients of greatest risk for gallbladder cancer before operation. After several elderly patients presenting with acute cholecystitis were found to have gallbladder cancer, we performed the following study. Records of patients (60 years of age or older, 1987 to 1995) with an admitting diagnosis of acute cholecystitis and symptoms including right upper quadrant pain, nausea, vomiting, fever, and leukocytosis were reviewed. Eighty patients were included in the study. Carcinoma involving the gallbladder was found in seven patients; six had primary and one had metastatic carcinoma. The 73 patients without cancer underwent cholecystectomy. The differences between the noncancer and cancer patients included age (68 +/- 7 versus 74 +/- 8 years, p < 0.05), total bilirubin (mg/dl, 1.5 +/- 1.5 versus 3.7 +/- 3.4, p < 0.01), alkaline phosphatase (IU/L, 179 +/- 132 versus 369 +/- 226, p < 0.01), and aspartate aminotransferase (IU/L, 77 +/- 93 versus 158 +/- 157, p < 0.05). Additional work-up and open cholecystectomy should be considered in elderly patients presenting with apparent acute cholecystitis, especially when liver functions are abnormal.

  18. Actinomycosis of the Gallbladder Mimicking Carcinoma: a Case Report with US and CT Findings

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    Lee, Young Han; Kim, Seong Hyun; Cho, Mee Yon; Rhoe, Byoung Seon; Kim, Myung Soon [Wonju Christian Hospital, Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)


    Actinomycosis should be included in the differential diagnosis when sonography and computed tomography findings show a mass engulfing the stone in the gallbladder and extensive pericholecystic infiltration with extension to neighboring abdominal wall muscle. A ctinomycosis is a chronic suppurative and granulomatous disease that is characterized by the formation of multiple abscesses, draining sinuses, abundant granulation and dense fibrous tissue. The disease is most frequently caused by Actinomyces israelii. These organisms are gram-positive anaerobic bacteria, and are considered opportunistic pathogens associated with infection, trauma or surgery. These events allow them to cross mucosal barriers as these organisms are normally present in healthy individuals, especially in the oral cavity, gastrointestinal tract, and female genital tract. In abdominopelvic actinomycosis, aggressive perilesional infiltration with a tendency to cross fascial planes or boundaries and extend to the abdominal wall has been well described as an important radiologic finding. Actinomycosis of the gallbladder is an extremely rare disease; only 21 cases have been reported in the English literature. Moreover, a diagnosis of actinomycosis of the gallbladder is difficult because this condition can be confused with carcinoma. We report here on a rare case of actinomycosis of the gallbladder that presented as a mass by sonography and computed tomography (CT)

  19. [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma]. (United States)

    Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji


    A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.

  20. Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma. (United States)

    Itano, Osamu; Oshima, Go; Minagawa, Takuya; Shinoda, Masahiro; Kitago, Minoru; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Ikoma, Naruhiko; Aiko, Satoshi; Kawaida, Miho; Masugi, Yohei; Kameyama, Kaori; Sakamoto, Michiie; Kitagawa, Yuko


    This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach. We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion. None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309 vs. 324 min, p = 0.755) and mean number of dissected lymph nodes (12.6 vs. 10.2, p = 0.361) were not significantly different between the LS and OS groups. The intraoperative blood loss was significantly lower (104 vs. 584 mL, p = 0.002) and the postoperative hospital stay was significantly shorter (9.1 vs. 21.6 days, p = 0.002) for LS patients than for those in the OS group. In the LS group, one patient developed postoperative pneumonia, but all patients survived without recurrence after a mean follow-up of 37 months. Our strategy for suspected T2 gallbladder GBC is safe and useful, avoids unnecessary procedures, and is associated with similar oncologic outcomes as the open method.

  1. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report. (United States)

    Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth


    At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Role of radical resection in patients with gallbladder carcinoma and jaundice. (United States)

    Feng, Fei-ling; Liu, Chen; Li, Bin; Zhang, Bai-he; Jiang, Xiao-qing


    Gallbladder carcinoma (GBC) is a commonly-seen malignancy of the biliary tract characterized by difficult early diagnosis, rapid growth, early metastasis, and poor prognosis. Nearly half of GBC patients also have jaundice, which is a mark of the advanced stage of GBC. The role of radical resection in patients of gallbladder carcinoma with jaundice is still a matter of uncertainty, which we attempted to clarify in this study. Totally, 251 GBC patients who received treatment at the Eastern Hepatobiliary Surgery Hospital (EHBH) from December 2002 to January 2010 were recruited into this study. We divided them into group A (jaundice group, n=117) and group B (non-jaundice group, n=134). Clinical records and follow-up data were collected and retrospectively analyzed in both groups. Compared with group A, patients in group B had a longer median survival time ((6.0±0.5) months vs. (15.0±2.6) months, Pjaundice (n=111), was still longer than that in patients with jaundice (n=116) (Pjaundice patients and non-jaundice patients; (12.0±4.3) months vs. (18.0±3.0) months (P>0.05). GBC with jaundice usually implies advanced stage disease and a poor prognosis for the patients. However, our findings indicate that as long as the patient's condition allows, radical resection is still feasible for GBC patients with jaundice, and may achieve a prognosis close to those GBC patients without jaundice.

  3. CCK1 receptor is involved in the regulation of protein lysine acetylation in GBC-SD cells and gallbladder carcinoma. (United States)

    Wu, W; Ouyang, B; Lu, Z; Liu, H; Tan, Y; Cui, P


    CCK1 (cholecystokinin receptor 1) and protein lysine acetylation were associated with several cancers, respectively. However, whether they are involved in the alternation of gallbladder carcinoma is unknown. This study investigated the characteristics of CCK1 and protein lysine acetylation in GBC-SD cells and carcinoma of gallbladder. The expression and localization of CCK1 were detected by western blot analysis and indirect immunofluorescence. GBC-SD cells were treated with CCK-8 and CCK-8+CCK1 inhibitor. The protein lysine acetylation from cells, as well as tissues of gallbladder carcinoma, was examined by western blotting. CCK1 receptor was expressed and localized in the GBC-SD cells. The synthetic octapeptide of CCK (CCK-8) could accelerate the lysine acetylation of a subset of proteins in dose-dependent manners in GBC-SD cells. Further investigation demonstrated that the specific inhibitor (CR1409) of CCK1 receptor could attenuate the CCK8-induced increase of protein lysine acetylation. In addition, we revealed that the rise of CCK1 receptor expression is associated with the increase of protein lysine acetylation in tissues from carcinoma of gallbladder. CCK might regulate protein lysine acetylation via CCK1 receptor.

  4. CPT-11 for bile-duct and gallbladder carcinoma: a phase II North Central Cancer Treatment Group (NCCTG) study. (United States)

    Alberts, Steven R; Fishkin, Paul A; Burgart, Lawrence J; Cera, Peter J; Mahoney, Michelle R; Morton, Roscoe F; Johnson, Patricia A; Nair, Suresh; Goldberg, Richard M


    Bile-duct and gallbladder carcinomas are rare cancers. Once they have spread beyond the point of surgical resectability, no therapies have shown meaningful long-term benefit. These cancers are typically refractory to standard chemotherapy agents. Based on preclinical work showing activity of CPT-11, we performed a phase II trial to assess its activity in patients with bile-duct or gallbladder carcinomas. Patients with histologic or cytologic evidence of locally advanced or metastatic bile-duct or gallbladder carcinoma were potentially eligible for this study. Patients meeting study eligibility and who signed an informed consent were given CPT-11 125 mg/m2 weekly for 4 wk followed by a 2-wk break from therapy. The starting dose of CPT-11 was later reduced to 100 mg/m2 grade IV toxicity. Patients continued on treatment if they showed evidence of benefit and tolerated therapy. A total of 39 patients were enrolled, and 36 were evaluable. The overall confirmed response rate was 8%. One CR and two PRs were seen. A high frequency of toxicity was seen. However, no unusual or unexpected toxicities occurred. CPT-11 is ineffective therapy for patients with locally advanced or metastatic bile-duct or gallbladder carcinoma.

  5. Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus. (United States)

    Weng, Mingzhe; Zhang, Mingdi; Qin, Yiyu; Gong, Wei; Tang, Zhaohui; Quan, Zhiwei; Wu, Kejin


    Gallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism. We performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery. We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV. This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.

  6. Diagnostic Imaging of Carcinomas of the Gallbladder and the Bile Ducts

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    Oikarinen, H. [Oulu Univ. Hospital (Finland). Dept. of Diagnostic Radiology


    Early diagnosis and accurate staging of carcinomas of the gallbladder and the bile ducts are helpful in improving the prognosis. Ultrasonography (US), a useful initial modality when exploring the background of jaundice or non-specific gastrointestinal complaints, sensitively reveals bile duct obstruction in particular. In unclear cases, or if US suggests a resectable biliary malignancy, computed tomography (CT), magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC) and/or traditional cholangiography often provide additional information, and imaging-guided fine-needle biopsy or an endoscopic brush sample may verify the malignant nature of the tumor. Complementary modalities are usually needed for accurate staging, and traditional cholangiography is often performed for therapeutic purposes as well. Comparative studies of MRI with MRC and multidetector CT in biliary cancers would be welcome.

  7. Six year disease free survival after liver transplantation in a patient with T3 gallbladder carcinoma: case presentation and review of the literature

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    Martinez Oscar


    Full Text Available Abstract Background The incidence of gallbladder carcinoma in cirrhotics is unknown. Known risk factors are primary sclerosing cholangitis and polypoid masses. Case presentation A sixty year old with primary sclerosing cholangitis, cirrhosis, and gallbladder polyps underwent liver transplantation. A polypoid lesion measuring 1.5 × 0.5 cm was found on the fundus of the gallbladder. Histological examination revealed moderately differentiated adenocarcinoma with full thickness penetration of the gallbladder encroaching liver parenchyma. Angiolymphatic invasion was noted. The lymph nodes, the cystic duct and the common duct were free of tumor (T3N0M0. Extensive evaluation did not demonstrate metastasis. No chemotherapy was given. He is currently six years post procedure and free of disease. Conclusion "Incidentally" discovered stage IIA gallbladder carcinoma may not negatively affect long term survival after liver transplantation.

  8. Gallbladder emptying response to sham feeding in humans

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    Fisher, R.S.; Rock, E.; Malmud, L.S.


    Cholescintigraphy, using 99mTc-HIDA, was employed to determine the gallbladder emptying response to sham feeding of a steak and potato meal, and to compare it with the emptying responses to direct cholinergic stimulation by bethanechol and to ingestion of the test meal. The maximal cumulative gallbladder emptying response to sham feeding was 44.1% + 10.1%, which was not significantly different from the response to bethanechol. Cholinergic blockade with atropine eliminated the emptying response to sham feeding. Also, sham feeding did not stimulate gallbladder emptying in patients with vagotomy. This study suggests that intact vagus nerves and cholinergic pathways are required in order for the gallbladder to respond to sham feeding. The precise mechanism for this effect has not been elucidated.

  9. Immunohistochemical Expression and Prognostic Value of CD97 and Its Ligand CD55 in Primary Gallbladder Carcinoma

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    Jinsheng Wu


    Full Text Available Background. CD97 as a member of the EGF-TM7 family with adhesive properties plays an important role in tumor aggressiveness by binding its cellular ligand CD55, which is a complement regulatory protein expressed by cells to protect them from bystander complement attack. Previous studies have shown that CD97 and CD55 both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. The aim of this study was to investigate CD97 and CD55 expression in primary gallbladder carcinoma (GBC and their prognostic significance. Methods. Immunohistochemistry was used to investigate the expression of CD97 and CD55 proteins in 138 patients with GBC. Results. CD97 and CD55 were absent or only weakly expressed in the normal epithelium of the gallbladder but in 69.6% (96/138 and 65.2% (90/138 of GBC, respectively, remarkably at the invasive front of the tumors. In addition, CD97 and CD55 expressions were both significantly associated with high histologic grade (both =0.009, advanced pathologic T stage (=0.01 and 0.009, resp. and clinical stage (both =0.009, and positive venous/lymphatic invasion (both =0.009. Multivariate analyses showed that CD97 (hazard ratio, 3.236; =0.02 and CD55 (hazard ratio, 3.209; =0.02 expressions and clinical stage (hazard ratio, 3.918; =0.01 were independent risk factor for overall survival. Conclusion. Our results provide convincing evidence for the first time that the expressions of CD97 and CD55 are both upregulated in human GBC. The expression levels of CD97 and CD55 in GBC were associated with the severity of the tumor. Furthermore, CD97 and CD55 expressions were independent poor prognostic factors for overall survival in patients with GBC.

  10. Overlap of Acute Cholecystitis with Gallstones and Squamous Cell Carcinoma of the Gallbladder in an Elderly Patient

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    İhsan Yıldız


    Full Text Available Introduction. The incidence of gallbladder cancer presenting with acute cholecystitis is 2.3%, squamous cell carcinoma is rarely seen, and overlap of acute cholecystitis and squamous cell carcinoma is a very rare condition in the literature. Presentation of Case. A 75-year-old woman was admitted to emergency service with a pain in the right upper quadrant, nausea, and vomiting. The patient was considered as having acute cholecystitis. During the exploration because Hartman’s pouch was not dissected, it was adhered to the cystic duct and had fibrotic adhesion. It could not be understood whether this adhesion was a tumor or a fibrotic tumor and thus we performed cholecystectomy with a 1 cm resection of the choledochus. Pathological examination revealed the presence of (R0, T1 N0 M0 squamous cell carcinoma with clean resection borders and there was no in tumor five dissected lymph nodes. The patient has been followed up for about two years and no clinical problem has been observed throughout the follow-up. Discussion. Acute cholecystitis with gallstones may overlap with gallbladder cancer and generally presents nonspecific symptoms. No additional imaging techniques were performed since no clinical sign except for the wall thickening was detected and no suspected malignancy such as mass was detected on USG. Squamous cell carcinoma of the gallbladder shows poor diagnosis, but since its overlap with cholecystitis presents early symptoms and thus leads to early diagnosis and effective treatment, the localization of the carcinoma is of prime importance. Conclusion. Gallbladder cancer should be kept in mind in elderly patients with acute cholecystitis.

  11. Primary carcinoma of the gallbladder: a review of a 16-year experience at the Waterbury Hospital Health Center. (United States)

    Shieh, C J; Dunn, E; Standard, J E


    The charts of 48 cases of primary carcinoma of the gallbladder seen at the Waterbury Hospital Health Center over the past 16 years were reviewed. In 47 patients, the diagnosis was confirmed pathologically. In one patient, the diagnosis was made only on clinical and radiologic grounds. This condition is more common in females and in the elderly (mean 71.7 years). Symptoms and signs were nonspecific, and duration of symptoms was extremely variable (range: one day to 21 years). There were 16.6% patients who had an associated primary tumor elsewhere. In 89.3% of the carcinomas of the gallbladder, the histologic type was adenocarcinoma. Two thirds of the patients had associated cholelithiasis. Overall five-year survival rate was 12.5%. In more than 80% of the patients, resection was made impossible by local invasion of liver, biliary ducts, and adjacent structures. Patients were divided into three groups according to the degree of invasion of the tumor. Group A had a survival rate of 66.6% at five years. There were no survivors in Group B and Group C. The different factors in each group are compared and discussed. Chemotherapy appeared to have no beneficial effect in the management of carcinoma of the gallbladder. Only one patient survived more than 12 months when tumor invaded the liver or the nodes along the biliary ducts. The postoperative complications and causes of death are also discussed.

  12. Evaluation of Tumor Markers and Their Impact on Prognosis in Gallbladder, Bile Duct and Cholangiocellular Carcinomas - A Pilot Study. (United States)

    Liska, Vaclav; Treska, Vladislav; Skalicky, Tomas; Fichtl, Jakub; Bruha, Jan; Vycital, Ondrej; Topolcan, Ondrej; Palek, Richard; Rosendorf, Jachym; Polivka, Jiri; Holubec, Lubos


    The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized. The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery. The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, pbile duct carcinoma, and cholangiocellular carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Primary Pure Squamous Cell Carcinoma of the Gallbladder Locally Invading the Liver, Duodenum, and Stomach: A Case Report and Literature Review

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    Aldrin C. Alpuerto


    Full Text Available Primary pure squamous cell carcinoma (SCC of the gallbladder is an exceptionally rare type of tumor that comprises only 1% of all gallbladder cancer. SCC of the gallbladder portends a worse prognosis than the more common adenocarcinoma variant because of its aggressive invasion to local structures and because it is often diagnosed at an advanced stage. Owing to its rarity, diagnosis and management can be challenging. Herein, we present the case of a 75-year-old female complaining of abdominal pain, nausea, and vomiting. Computed tomography and ultrasonography results of the abdomen were consistent with acute cholecystitis and cholelithiasis. Histologic evaluation of the resected mass revealed a malignant tumor with prominent keratinization, confirming the diagnosis of an invasive primary pure SCC of the gallbladder. Microscopic examination showed direct infiltration to the liver, duodenum, and stomach. This case report describes the hospital course of a patient with SCC of the gallbladder and suggests that gallbladder cancer should be considered as part of the differential diagnosis in elderly patients presenting with acute cholecystitis. In addition, this article will review existing literature to examine the utility of different diagnostic techniques and treatment modalities available in the management of gallbladder cancer.

  14. Gallbladder Cancer (United States)

    ... your gallbladder and liver to your small intestine. Cancer of the gallbladder is rare. It is more ... the abdomen It is hard to diagnose gallbladder cancer in its early stages. Sometimes doctors find it ...

  15. [Gender-specific influencing factors on incidence, risk factors and outcome of carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas]. (United States)

    Grundmann, R T; Meyer, F


    This overview comments on gender-specific differences in incidence, risk factors and prognosis in patients with carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas. For the literature review, the MEDLINE database (PubMed) was searched under the key words "liver cancer", "gallbladder cancer", "extrahepatic bile duct carcinoma", "pancreatic cancer" AND "gender". There were significant gender differences in the epidemiology of the analysed carcinomas. The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women, one of 86 men, but only 1 out of 200 women develop a malignant primary liver tumour in Germany in the course of their life. The lifetime risk for carcinomas of the gallbladder and extrahepatic bile ducts in Germany amounts to about 0.6 % for women and 0.5 % for men, specifically gallbladder carcinomas are observed more frequently in women than in men. For pancreatic cancer, no clear gender preference exists in Germany, although the mortality risk for men is higher than that for women (age-adjusted standardised death rate in men 12.8/100, 000 persons, in women 9.5). Remarkable is furthermore the shift of the tumour incidence in the last decades. Liver cancer has increased among men in Germany by about 50 % in the last 30 years, the incidence of gallbladder carcinoma has inversely dropped. The prognosis of these cancers across all tumour stages is uniformly bad in an unselected patient population. This is probably the main reason why only little - if any - gender differences in survival are described. In addition to avoiding the known risk factors such as hepatitis B and C virus infection, alcohol abuse, and smoking, the avoidance of overweight and obesity plays an increasingly important role in the prevention of these cancers. Georg Thieme Verlag KG Stuttgart · New York.

  16. (1)H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation. (United States)

    Sharma, Raj Kumar; Mishra, Kumudesh; Farooqui, Alvina; Behari, Anu; Kapoor, Vinay Kumar; Sinha, Neeraj


    We present in this article (1)H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). (1)H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation. Receiver operating curve (ROC) and pathway analysis on NMR data were also carried out to validate the findings. Serum metabolites such as glutamine, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), alanine, branch chained amino acids (BCAA), histidine and tyrosine were found to be depleted whereas formate, lactate, 1,2-propanediol were found to be elevated in CC. Metabolic pathways associated with metabolite alteration have also been reported. NMR has been established for disease diagnosis along with identification of metabolic pattern recognition in biofluids. Gallstones cause inflammation of the gallbladder in the form of CC. Inflammation plays a major role in causation of gall bladder cancer and leads the way to malignancy. Metabolic analysis of CC may lead to early diagnosis of disease and its progression to gallbladder cancer.

  17. The effect of lysolecithin on prostanoid and platelet-activating factor formation by human gall-bladder mucosal cells

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    M. K. Nag


    Full Text Available It has been demonstrated that lysolecithin (lysophosphatidyl choline, LPC produces experimental cholecystitis in cats mediated by arachidonic acid metabolites. LPC is a cytolytic agent that has been postulated as a contributing factor in the development of cholecystitis in humans. The purpose of this research was to evaluate the effect of LPC on human gall-bladder mucosal cell phospholipase A2 and cyclooxygenase activity. Gall-bladder mucosal cells were isolated from the gall-bladders of patients undergoing routine cholecystectomy. Fresh, isolated cells were maintained in tissue culture and stimulated with varying doses of LPC. Platelet-activating factor concentration was quantitated as an index of phospholipase A2 activity and prostanoids were measured as an index of cyclooxygenase activity. Also, the effect of LPC on cyclooxygenase 1 and 2 expression in microsomal protein was evaluated. LPC caused dose related increases in 6-keto-PGF1α and PAF produced by human gall-bladder mucosal cells. Exposure of human gall-bladder mucosal cells to LPC failed to elicit expression of constitutive cyclooxygenase-1, while the expression of inducible cyclooxygenase-2 was increased. The results of this study indicate that LPC induces the formation of prostanoids and PAF by human gall-bladder mucosal cells, suggesting that this substance may promote the development of gall-bladder inflammation.

  18. Guidance to rational use of pharmaceuticals in gallbladder sarcomatoid carcinoma using patient-derived cancer cells and whole exome sequencing. (United States)

    Feng, Feiling; Cheng, Qingbao; Yang, Liang; Zhang, Dadong; Ji, Shunlong; Zhang, Qiangzu; Lin, Yihui; Li, Fugen; Xiong, Lei; Liu, Chen; Jiang, Xiaoqing


    Gallbladder sarcomatoid carcinoma is a rare cancer with no clinical standard treatment. With the rapid development of next generation sequencing, it has been able to provide reasonable treatment options for patients based on genetic variations. However, most cancer drugs are not approval for gallbladder sarcomatoid carcinoma indications. The correlation between drug response and a genetic variation needs to be further elucidated. Three patient-derived cells-JXQ-3D-001, JXQ-3D-002, and JXQ-3D-003, were derived from biopsy samples of one gallbladder sarcomatoid carcinoma patient with progression and have been characterized. In order to study the relationship between drug sensitivity and gene alteration, genetic mutations of three patient-derived cells were discovered by whole exome sequencing, and drug screening has been performed based on the gene alterations and related signaling pathways that are associated with drug targets. It has been found that there are differences in biological characteristics such as morphology, cell proliferation, cell migration and colony formation activity among these three patient-derived cells although they are derived from the same patient. Their sensitivities to the chemotherapy drugs-Fluorouracil, Doxorubicin, and Cisplatin are distinct. Moreover, none of common chemotherapy drugs could inhibit the proliferations of all three patient-derived cells. Comprehensive analysis of their whole exome sequencing demonstrated that tumor-associated genes TP53, AKT2, FGFR3, FGF10, SDHA, and PI3KCA were mutated or amplified. Part of these alterations are actionable. By screening a set of compounds that are associated with the genetic alteration, it has been found that GDC-0941 and PF-04691502 for PI3K-AKT-mTOR pathway inhibitors could dramatically decrease the proliferation of three patient-derived cells. Importantly, expression of phosphorylated AKT and phosphorylated S6 were markedly decreased after treatments with PI3K-AKT-mTOR pathway

  19. A case report of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast

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    David Brinkman


    Conclusion: Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma is an uncommon presentation to surgeons. A diagnostic laparoscopy is the preferred initial evaluation. If deemed feasible, and if the surgeon has the required experience, a laparoscopic cholecystectomy can be undertaken selectively.

  20. S0514 Sorafenib in Treating Patients With Unresectable or Metastatic Gallbladder Cancer or Cholangiocarcinoma (United States)


    Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Squamous Cell Carcinoma of the Gallbladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  1. Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary (United States)

    Nagahashi, Masayuki; Ajioka, Yoichi; Lang, Istvan; Szentirmay, Zoltan; Kasler, Miklos; Nakadaira, Hiroto; Yokoyama, Naoyuki; Watanabe, Gen; Nishikura, Ken; Wakai, Toshifumi; Shirai, Yoshio; Hatakeyama, Katsuyoshi; Yamamoto, Masaharu


    AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis. PMID:18176964

  2. A case report of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast. (United States)

    Brinkman, David; Misra, Subhasis; Aydin, Nail


    Invasive lobular carcinoma is the second most common type of breast cancer, responsible for 5-15 percent of all cases. Peritoneal carcinomatosis secondary to breast cancer is a rare event, frequently resulting in morbidity and mortality. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast is a very rare event and is not well covered in literature. A 44year old female patient previously diagnosed with stage IV invasive lobular carcinoma of the left breast with widespread systemic metastases and peritoneal carcinomatosis presented with a three week history of right upper quadrant pain trigged by food intake only, greatly diminishing her quality of life. She had spent almost a year in a progression free disease status but was now suffering from debilitating symptomatic gallbladder disease. Despite the extent of her peritoneal carcinomatosis, she elected to undergo a laparoscopic cholecystectomy. We are presenting a rare case of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma. A major concern is tumor load within nearby portal structures. Even though laparoscopic cholecystectomy could be a viable option to treat the condition, it needs to be applied selectively and very cautiously in the respective patient population. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma is an uncommon presentation to surgeons. A diagnostic laparoscopy is the preferred initial evaluation. If deemed feasible, and if the surgeon has the required experience, a laparoscopic cholecystectomy can be undertaken selectively. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Gallbladder duplication

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    Yagan Pillay


    Conclusion: Duplication of the gallbladder is a rare congenital abnormality, which requires special attention to the biliary ductal and arterial anatomy. Laparoscopic cholecystectomy with intraoperative cholangiography is the appropriate treatment in a symptomatic gallbladder. The removal of an asymptomatic double gallbladder remains controversial.

  4. Hepatic resection for T2-3 gallbladder carcinoma: a retrospective analysis of 12 resectable cases

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    Manlio Basílio Speranzini


    Full Text Available Objective: To report on a group of 12 patients with advanced gallbladder adenocarcinoma at a General Hospital and describe the outcomes (surgical morbidity - mortality and long-term survival following hepatic resection. Methods: The authors present a series of twelve patients with invasive gallbladder adenocarcinoma who underwent hepatic resection at the General Surgery Service of the Hospital de Ensino da Faculdade de Medicina do ABC, in Santo Andre. The study period was from 2001 to 2007. There were twelve hepatic resections, all associated with hilar lymphadenectomy (IVB-V bisegmentectomy = 9 and right trisectionectomy = 3. There were ten women and two men and all patients were Caucasian. The age range was 52 to 72 years. The preoperative symptoms were biliary colic (n = 6, dyspepsia (n = 4, acute cholecystitis (n = 1 and jaundice (n = 1. The diagnosis was made by radiographic images in the preoperative period in seven patients; all of them were confirmed by frozen section during surgery. Five patients submitted to open cholecystectomy (n = 4 and laparoscopic cholecystectomy (n  = 1 had their diagnoses confirmed postoperatively by histological analysis. Rresults: The operative time varied between 180 and 340 minutes. Four patients received transfusions. The blood loss varied between 200 and 2500 ml. The hospital stay varied from 7 to 16 days. There were two major complications in two patients and both were treated conservatively, one biliary leakage and one reversible hepatic failure. There was no mortality. The TNM stage distribution was: T2N0M0 (n = 4, T2N1M0 (n = 2, T3N0M0 (n = 4 and T3N1M0 (n = 2. Only one patient presented affected surgical margin (T3N1M0 and died with both peritoneal and liver recurrence after a 9-month follow-up. Other three patients presented recurrence(13 to 28 months of follow-up and died. The three-year survival rate was 33.3% (n  = 4. Cconclusion: The radical surgical treatment with hepatectomy plus hilar

  5. The dominating macromolecular complex of human gallbladder bile

    NARCIS (Netherlands)

    Verschure, J.C.M.; Mijnlieff, P.F.

    The solutes of human gall bladder bile appear to exist mainly in the form of a complex macromolecule, formed around a nucleus of lipoprotein. The existence of this macromolecule was demonstrated by paper electrophoresis1, free electrophoresis and ultracentrifuge experiments. The molecular weight of

  6. Gallbladder carcinoma: clinicopathological study of 24 cases Carcinoma da vesícula biliar: estudo clinicopatológico de 24 casos

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    Moema Gonçalves Pinheiro Veloso


    Full Text Available INTRODUCTION: Despite preoperative procedures, gallbladder carcinoma is commonly detected intraoperatively or on anatomopathologic examination after cholecystectomy. OBJECTIVE: To study the clinical-morphological aspects and evolution of patients with primary gallbladder carcinoma. METHODS: We reviewed medical records and pathologic material of all patients diagnosed with gallbladder carcinoma at our institution from 1997 to 2008. RESULTS: Twenty-four cases with primary carcinoma were studied, predominantly among female patients, mean age of 61.1 years. The most common clinical symptom was upper right hypochondriac pain. Five patients were diagnosed in early stages and 19 were in advanced stages. Only seven patients were diagnosed with carcinoma preoperatively, all of them in advanced stages. As to macroscopic examination, three early cases were identified as type IIa, two type IIb and 13 advanced cases were flat and infiltrating. Histologically, there were 23 adenocarcinomas and one adenosquamous carcinoma. Simple cholecystectomy was performed in seven patients, extended cholecystectomy in four patients, cholecystectomy and omentectomy in one patient, and tumor biopsy in only two patients. The median survival rate for patients in early stages was 59 months, and for pT2, pT3 and pT4 stages were 22 months, nine months and three days, respectively. CONCLUSION: There was a prevalence of advanced neoplasias diagnosed through anatomopathological examinations with poor prognosis. Furthermore, earlier detection contributed to higher survival rate. Investigation of anatomopathologic features, specially the macroscopic patterns of gallbladder carcinoma, is essential to improve diagnostic accuracy and to provide a definite treatment.INTRODUÇÃO: Não obstante estudos pré-operatórios, o câncer da vesícula biliar é frequentemente detectado durante a cirurgia ou no exame anatomopatológico após colecistectomias. OBJETIVO: Avaliar as principais

  7. AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines

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    Leal P


    Full Text Available Pamela Leal,1,* Patricia Garcia,2,* Alejandra Sandoval,1 Kurt Buchegger,1 Helga Weber,1 Oscar Tapia,1 Juan C Roa1,2 1Department of Pathology, Universidad de La Frontera, Center of Genetical and Immunological Studies-Scientific and Technological Bioresource Nucleus, Temuco, 2Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile *These authors contributed equally to this paperBackground: Gallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines.Methods: Immunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression.Results: Our results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18, early cancer (84.6%, 22/26, and advanced cancer (88.3%, 121/137. No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall

  8. Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis. (United States)

    Kim, Byoung Hyuck; Kwon, Jeanny; Chie, Eui Kyu; Kim, Kyubo; Kim, Young Hoon; Seo, Dong Wan; Narang, Amol K; Herman, Joseph M


    The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

  9. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni


    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... of the role of vitronectin in tumour biology in interaction with the plasminogen activation system and integrins....

  10. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial

    NARCIS (Netherlands)

    Stein, Alexander; Arnold, Dirk; Bridgewater, John; Goldstein, David; Jensen, Lars Henrik; Klümpen, Heinz-Josef; Lohse, Ansgar W.; Nashan, Björn; Primrose, John; Schrum, Silke; Shannon, Jenny; Vettorazzi, Eik; Wege, Henning


    Despite complete resection, disease-free survival (DFS) of patients with cholangiocarcinoma (CCA) is less than 65 % after one year and not more than 35 % after three years. For muscle invasive gallbladder carcinoma (GBCA), prognosis is even worse, with an overall survival (OS) of only 30 % after

  11. Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections. (United States)

    Ober, Michael C; Hoppe-Tichy, Torsten; Köninger, Jörg; Schunter, Oliver; Sonntag, Hans-Günther; Weigand, Markus A; Encke, Jens; Gutt, Carsten; Swoboda, Stefanie


    Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

  12. A comparative study of clinicopathological significance, FGFBP1, and WISP-2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder. (United States)

    Yang, Zhulin; Yang, Zhi; Zou, Qiong; Yuan, Yuan; Li, Jinghe; Li, Daiqiang; Liang, Lufeng; Zeng, Guixiang; Chen, Senlin


    The differences in clinical, pathological, and biological characteristics between adenocarcinoma (AC) and squamous cell/adenosquamous carcinoma (SC/ASC) of gallbladder cancer have not been well documented. This study is to compare the clinicopathological characteristics and FGFBP1 and WISP-2 expression between AC and SC/ASC patients. We examined FGFBP1 and WISP-2 expression in 46 SC/ASC and 80 AC samples using immunohistochemistry and analyzed their correlations with clinicopathological characteristics. SC/ASCs occur more frequently in older patients and often correspond to larger tumor masses than ACs. Positive FGFBP1 and negative WISP-2 expression were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. In addition, positive FGFBP1 and negative WISP-2 expression were significantly associated with differentiation and TMN stage in ACs. Univariate Kaplan-Meier analysis showed that either elevated FGFBP1 (p WISP-2 (p WISP-2 expression (p = 0.035 for SC/ASC and p = 0.009 for AC) is an independent predictor of poor prognosis in both SC/ASC and AC patients. We also revealed that differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical procedure were associated with survival of both SC/ASC and AC patients. Our study suggested that the overexpression of FGFBP1 or loss of WISP-2 expression is closely related to the metastasis, invasion and poor prognosis of gallbladder cancer.

  13. Treatment Option Overview (Gallbladder Cancer) (United States)

    ... History Committees of Interest Legislative Resources Recent Public Laws Careers Visitor Information Search Search Home Cancer Types Gallbladder Cancer Patient Gallbladder Cancer Patient Gallbladder ...


    Directory of Open Access Journals (Sweden)

    Malina Mitić


    Full Text Available Precancerous conditions in the gallbladder are still a matter of interest of numerous investigators, but reliable and definite attitude is not jet available. Particularly, many regenerative/reparative changes during inflammation and cholelithiasis in the gallbladder cannot be classified with certainty as lesions which precede malignant alteration. However, it is considered that metaplastic-dysplastic changes, which appear in mucosa and can lead to malignant neoplasia, are one of the ways of cancer morphogenesis. This way is considered as non-neoplastic way of gallbladder carcinoma development. The other way of cancer genesis goes through precancerous neoplasia, i.e. adenoma.The aim of this article was to, upon a polyp found in the gallbladder after cholecystectomy in a 70-year-old patient, determine one of the ways of gallbladder carcinoma morphogenesis.Cholecystectomy was done after ultrasound finding of the gallbladder polyp. Macroscopically and microscopically, it was the intestinal type of villous adenoma with the third degree epithelial dysplasia, which designates that this adenoma has reliable signs for precancerous lesion, and confirms the adenoma-carcinoma sequence theory, already characteristic for large intestine, the opinion the authors agree with.

  15. Detecting gallbladders in chicken livers using spectral analysis

    DEFF Research Database (Denmark)

    Jørgensen, Anders; Mølvig Jensen, Eigil; Moeslund, Thomas B.


    This paper presents a method for detecting gallbladders attached to chicken livers using spectral imaging. Gallbladders can contaminate good livers, making them unfit for human consumption. A data set consisting of chicken livers with and without gallbladders, has been captured using 33 wavelengt...

  16. Human gallbladder pressure and volume: validation of a new direct method for measurements of gallbladder pressure in patients with acute cholecystitis

    DEFF Research Database (Denmark)

    Borly, L; Højgaard, L; Grønvall, S


    Increased gallbladder (GB) pressure is probably a part of the pathogenesis of acute cholecystitis, and measurements of GB pressure might therefore be of interest. The aim of this study was to validate a microtip pressure transducer for intraluminal GB pressure measurements. In vitro precision...... and accuracy was within 0.2 mmHg, (SD) and 0.6 +/- 0.1 mmHg (mean +/- SD), respectively. Pressure rise rate was 24.8 +/- 5.5 mmHg s-1. Zero drift was in the range 0.3 +/- 0.4 to 0.8 +/- 0.9 mmHg (mean +/- SD). GB pressure was investigated in 16 patients with acute cholecystitis treated with percutaneous...

  17. Primary Leiomyosarcoma of Gallbladder: A Rare Diagnosis

    Directory of Open Access Journals (Sweden)

    Ajay Savlania


    Full Text Available Leiomyosarcoma of the gallbladder is a rare entity, constituting about 1.4 per 1000 gallbladder malignancies. Literature review shows female preponderance in sixth decade of life, due to unknown reasons. We report one such rare case of a 50-year-old female admitted with pain in right upper abdomen. On examination, mass was felt in right hypochondrium. The ultrasound abdomen showed mass with loss of interface with liver and cholelithiasis. CECT abdomen showed polypoidal gallbladder malignancy with ill-defined interface with liver. She was operated upon with diagnosis of carcinoma gallbladder; extended cholecystectomy was done. Histopathological examination revealed spindle-cell proliferation and possibility of malignant tumor of mesenchymal origin was kept. This was later confirmed on immunohistochemistry.

  18. Primary Leiomyosarcoma of Gallbladder: A Rare Diagnosis (United States)

    Savlania, Ajay; Behera, Arunanshu; Vaiphei, Kim; Singh, Harjeet; Dhiman, R. K.; Duseja, Ajay; Chawla, Y. K.


    Leiomyosarcoma of the gallbladder is a rare entity, constituting about 1.4 per 1000 gallbladder malignancies. Literature review shows female preponderance in sixth decade of life, due to unknown reasons. We report one such rare case of a 50-year-old female admitted with pain in right upper abdomen. On examination, mass was felt in right hypochondrium. The ultrasound abdomen showed mass with loss of interface with liver and cholelithiasis. CECT abdomen showed polypoidal gallbladder malignancy with ill-defined interface with liver. She was operated upon with diagnosis of carcinoma gallbladder; extended cholecystectomy was done. Histopathological examination revealed spindle-cell proliferation and possibility of malignant tumor of mesenchymal origin was kept. This was later confirmed on immunohistochemistry. PMID:22900213

  19. Diet After Gallbladder Removal (United States)

    ... keep having diarrhea. Is there a gallbladder removal diet I should follow? Answers from Katherine Zeratsky, R. ... months. There isn't a specific gallbladder removal diet that you should follow, but there are a ...

  20. Gallbladder torsion. Case report

    DEFF Research Database (Denmark)

    Brasso, K; Rasmussen, O V


    Gallbladder torsion is a rare surgical emergency occurring primarily in elderly women. The anatomical background is a variation in the attachment of the gallbladder to the inferior margin of the liver. Increasing life span will probably lead to an increasing number of cases, and gallbladder torsion...

  1. Surgical treatment of gallbladder polypoid lesions

    Directory of Open Access Journals (Sweden)

    Pejić Miljko A.


    Full Text Available INTRODUCTION Polypoid lesions of the gallbladder can be divided into benign and malignant categories. Malignant polypoid lesions include carcinomas of the gallbladder, which is the fifth most common malignancy of the gastrointestinal tract and the most common malignancy of the biliary tract. Benign polypoid lesions of the gallbladder are divided into true tumors and pseudotumors. Pseudotumors account for most of polypoid lesions of the gallbladder, and include polyps, hyperplasia, and other miscellaneous lesions. Adenomas are the most common benign neoplasms of the gallbladder. Cholesterol polyps are the most common pseudotumors of the gallbladder. The polyps can be single or multiple, usually less than 10 mm in size. They have no predilection for any particular gallbladder site, and usually are attached to the gallbladder wall by a delicate, narrow pedicle. No malignant potential has been identified for this type of pseudotumor. Adenomas are the most common benign neoplasms of the gallbladder. They have no predilection site in the gallbladder, and may also be associated with gallstones or cholecystitis. The premalignant nature of adenomas remains controversial. Ultrasonography (US has been demonstrated to be significantly better in detecting polypoid lesions of the gallbladder as compared with computed tomography and cholecystography. A mass fixed to the gallbladder wall of normal thickness, without shadowing, is seen in case of gallbladder polyp. Since gallbladder cancers usually present as polypoid lesions, differentiation between benign polypoid lesion and malignant lesion can be very difficult, even with high-resolution imaging techniques. PATIENTS AND METHODS Retrospectively we have analyzed 38 patients with ultrasonographicaly detected gallbladder polyps during the period from January 1995 to December 2000, who were treated at surgical department of Health Centre in Uzice and at Surgical clinic of Clinical Centre in Nis. We have analyzed

  2. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  3. The human gallbladder secretes fibroblast growth factor 19 into bile: towards defining the role of fibroblast growth factor 19 in the enterobiliary tract. (United States)

    Zweers, Serge J L B; Booij, Klaske A C; Komuta, Mina; Roskams, Tania; Gouma, Dirk J; Jansen, Peter L M; Schaap, Frank G


    Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback regulation of bile salt synthesis. In the postprandial state, activation of ileal farnesoid X receptor (FXR) by bile salts results in transcriptional induction of FGF19 and elevation of circulating FGF19 levels. An intestinal-liver axis of FGF19 signaling results in down-regulation of bile salt synthesis. The aim of this study was to explore a broader signaling activity of FGF19 in organs engaged in the enterohepatic circulation of bile salts. For this aim, FGF19 expression and aspects of FGF19 signaling were studied in surgical specimens and in cell lines of hepatobiliary and intestinal origin. FGF19 messenger RNA was found to be abundantly expressed in the human gallbladder and in the common bile duct, with only minor expression observed in the ileum. Interestingly, human gallbladder bile contains high levels of FGF19 (21.9 ± 13.3 versus 0.22 ± 0.14 ng/mL in the systemic circulation). Gallbladder explants secrete 500 times more FGF19 than FXR agonist-stimulated ileal explants. Factors required for FGF19 signaling (i.e., FGFR4 and βKlotho) are expressed in mucosal epithelial cells of the gallbladder and small intestine. FGF19 was found to activate signaling pathways in cell lines of cholangiocytic, enteroendocrine, and enterocytic origin. The combined findings raise the intriguing possibility that biliary FGF19 has a signaling function in the biliary tract that differs from its established signaling function in the portal circulation. Delineation of the target cells in bile-exposed tissues and the affected cellular pathways, as well as a possible involvement in biliary tract disorders, require further studies. Copyright © 2011 American Association for the Study of Liver Diseases.

  4. Incidental gallbladder cancer: what management?

    Directory of Open Access Journals (Sweden)

    Sidi Mohammed Bouchentouf


    Full Text Available Gallbladder cancer (GBC represents 3.8% of all gastrointestinal cancers and usually known to be of a poor prognosis. In 0.2–2.9% of cases, this cancer is found in cholecystectomy specimens. A better understanding of spread mode of this tumor helps a better surgical management. The aim of the present review is to underline the management of GBC based on the comprehension of risk factors and anatomic features. A Medline, PubMed database search was performed to identify articles published from 2000 to 2011 using the keywords ‘carcinoma of gallbladder’, ‘incidental gallbladder cancer’, ‘gallbladder neoplasm’ and ‘cholecystectomy’. Some pathological situations such as chronic lithiasis and biliopancreatic junction abnormalities have been clearly identified as predisposing to GBC. Laparoscopy increases peritoneal and parietal tumor dissemination, thus, it should not be performed when GBC is suspected. Most determinant prognostic factors are nodal, perineural and venous involvement, invasion of the cystic duct and the tumor differentiation. The simple cholecystectomy is sufficient for tumors classified as T1a; for other cancers exceeding the muscularis, radical re-resection is required due to the high risk of recurrence. This aggressive surgery improved the overall survival of patients. There is still no standard adjuvant treatment; patients should be included in prospective trials.

  5. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial

    DEFF Research Database (Denmark)

    Stein, A.; Arnold, D.; Bridgewater, J.


    Background: Despite complete resection, disease-free survival (DFS) of patients with cholangiocarcinoma (CCA) is less than 65 % after one year and not more than 35 % after three years. For muscle invasive gallbladder carcinoma (GBCA), prognosis is even worse, with an overall survival (OS) of only....... Due to the different prognosis and treatment susceptibility of muscle invasive carcinoma, two separate cohorts (CCA and GBCA) were included to capture the potentially different treatment effects. Randomization is stratified for lymph node status for both cohorts and localization for CCA. The primary...... endpoint is DFS and secondary endpoints include OS, safety and tolerability of chemotherapy, quality of life, and patterns of disease recurrence. For CCA, adjuvant chemotherapy should increase DFS 24 months post-surgery from 40 to 55 % to be considered relevant. With a power of 80 % and a significance...

  6. Primary leiomyosarcoma of gallbladder (United States)

    Park, Eun Young; Yun, Sung Pil; Kim, Suk; Kim, Joo Yeun; Han, Koon Taek


    Malignant mesenchymalneoplasms of the gallbladder are extremely rare with only 105 cases of primary gallbladder sarcoma having been described. It has a very aggressive behavior and is usually diagnosed at advanced stages. Therefore, curative surgical management may not be possible. We performed a radical cholecystectomy (S4b + S5 segmentectomy), omentectomy and small bowel resection in a 54-year-old patient with locally invasive leiomyosarcoma of the gallbladder. Further studies are needed to confirm the benefit of aggressive treatment for patients with leiomyosarcoma of the gallbladder. PMID:23230561

  7. The Helicobacter pylori L-form: formation and isolation in the human bile cultures in vitro and in the gallbladders of patients with biliary diseases. (United States)

    Wang, Dan N; Ding, Wen J; Pan, Yao Z; Tang, Ke L; Wang, Tao; She, Xiao L; Wang, He


    The Helicobacter pylori is considered the important causative agent causing biliary diseases, but the H. pylori can be isolated from very few gallbladder specimens with diseases. We studied the formation of H. pylori L-forms in bile in vitro and isolated the H. pylori L-forms from gallbladder of patients with biliary diseases. We inoculated the H. pylori into the human bile to induce the L-form in vitro. The gallbladder specimens were collected from patients with biliary diseases to isolate the bacterial L-forms by the nonhigh osmotic isolation technique, and the H. pylori L-forms in the L-form isolates were identified by the gene assay for the H. pylori-specific genes 16S rRNA and UreA. The H. Pylori cannot be isolated from the bile-induced cultures, but the H. pylori L-form can be isolated from the H. pylori-negative bile-induced cultures. The L-form isolates of bile-induced cultures showed a positive reaction of the H. pylori-specific genes by PCR, and the coincidence ratio of the nucleotide sequences between the L-forms and the H. pylori is 99%. The isolation rate of bacteria L-form is 93.2% in the gallbladder specimens with bacteria-negative isolation culture by the nonhigh osmotic isolation technique, and the positive rate of the H. pylori-specific genes in the L-form isolates is 7.1% in the bacterial L-form-positive isolation cultures by the PCR. H. pylori can be rapidly induced into the L-form in the human bile; the L-form, as the latent bacteria, can live in the host gallbladder for a long times, and they made the host became a latent carrier of the H. pylori L-form. The H. pylori L-form can be isolated by the nonhigh osmotic isolation technique, and the variant can be identified by the gene assay for the H. pylori-specific genes 16S rRNA and reA. © 2014 John Wiley & Sons Ltd.

  8. Molecular Genetic Study of Human Esophageal Carcinoma (United States)


    virus have been shown to be the causative agent for human cancer, as human papilloma - virus ( HPV ) was associated with...F.J., Syrjanen, S., Shen, Q., J.I, H., & Kyrjanen, K. Human papilloma virus ( HPV ) DNA in esophageal precursor lesions and squamous cell carcinomas...genital tumors. Gene products, such as SV40 tumor antigen, Ela and Elb in adenovirus, E6 and E7 protein of human papilloma virus type 16 and type

  9. Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder. (United States)

    Legan, Mateja; Tevžič, Spela; Tolar, Ana; Luzar, Boštjan; Marolt, Vera Ferlan


    GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.

  10. Influence of age on gallbladder morphometry | Kariuki | Anatomy ...

    African Journals Online (AJOL)

    Ninety-two gallbladder specimens of subjects aged between 21 and 84 were sourced from City mortuary and the Department of Human anatomy during autopsy. For each gallbladder specimen, measurements of length and circumference were taken to the accuracy of 0.1millimetres (mm) and used to calculate the ...

  11. Gall-bladder sludge: lessons from ceftriaxone. (United States)

    Kim, Y S; Kestell, M F; Lee, S P


    Ceftriaxone-associated sludge has been a fascinating story. The occurrence is novel and unique. It has produced a model of gall-bladder sludge in humans. This phenomenon has taught us a great deal about biliary lipid and organic anion excretion by the liver, and the physical chemistry of calcium and calcium sensitive anions. It has added further insights into the pathophysiology of gall-bladder sludge formation. It points to a combination of a hepatic effect where the liver secretes a biochemically abnormal bile, and a gall-bladder effect which provides an environment for precipitation, in order for sludge to develop. The precipitated calcium ceftriaxone has prompted us to re-evaluate the imaging criteria for the diagnosis of gall-bladder sludge versus gallstones. Above all, the rapid onset and rapid disappearance of ceftriaxone sludge has mirrored in a compressed, encapsulated form, the natural history of gall-bladder sludge. It has reminded us that, like gallstones, biliary sludge is usually benign and asymptomatic. However just because it is smaller than gallstones does not mean it cannot cause problems. It can disappear or it can become a calcium ceftriaxone gallstone.

  12. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. (United States)

    Sharma, Aarti; Sharma, Kiran Lata; Gupta, Annapurna; Yadav, Alka; Kumar, Ashok


    Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed ( Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (,, Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

  13. Gradual Recovery from Nonambulatory Quadriparesis Caused by Metastatic Epidural Cervical Cord Compression in an Octogenarian Gallbladder Carcinoma Patient Treated with Image-Guided Three-Dimensional Conformal Radiotherapy Alone Using a Field-in-Field Technique

    Directory of Open Access Journals (Sweden)

    Kazuhiro Ohtakara


    Full Text Available Radiotherapy for acute metastatic epidural spinal cord compression (MESCC involves conventional techniques and dose fractionation schemes, as it needs to be initiated quickly. However, even with rapid intervention, few paraplegic patients regain ambulation. Here, we describe the case of a mid-octogenarian who presented with severe pain and nonambulatory quadriparesis attributable to MESCC at the fifth cervical vertebra, which developed 10 months after the diagnosis of undifferentiated carcinoma of the gallbladder. Image-guided three-dimensional conformal radiotherapy (IG-3DCRT was started with 25 Gy in 5 fractions followed by a boost of 12 Gy in 3 fractions, for which a field-in-field (FIF technique was used to optimize the dose distribution. Despite the fact that steroids were not administered, the patient reported significant pain reduction and showed improved motor function 3 and 4 weeks after the IG-3DCRT, respectively. Over the following 4 months, her neurological function gradually improved, and she was consequently able to eat and change clothes without assistance and to walk slowly for 10–20 m using a walker. She succumbed to progression of abdominal disease 8.5 months after the IG-3DCRT. This case demonstrates that image-guided FIF radiotherapy with a dose-escalated hypofractionated regimen can potentially improve functional outcome and local control.

  14. Routine histopathology of gallbladder after elective cholecystectomy for gallstones: waste of resources or a justified act? (United States)

    Siddiqui, Faisal G; Memon, Ahmer A; Abro, Arshad H; Sasoli, Nazeer A; Ahmad, Lubna


    Selective approach for sending cholecystectomy specimens for histopathology results in missing discrete pathologies such as premalignant benign lesions such as porcelain gallbladder, carcinoma-in-situ, and early carcinomas. To avoid such blunders therefore, every cholecystectomy specimen should be routinely examined histologically. Unfortunately, the practice of discarding gallbladder specimen is standard in most tertiary care hospitals of Pakistan including the primary investigators' own institution. This study was conducted to assess the feasibility or otherwise of performing histopathology in every specimen of gallbladder. This cohort study included 220 patients with gallstones for cholecystectomy. All cases with known secondaries from gallbladder, local invasion from other viscera, traumatic rupture of gallbladder, gross malignancy of gallbladder found during surgery was excluded from the study. Laparoscopic cholecystectomy was performed in majority of cases except in those cases where anatomical distortion and dense adhesions prevented laparoscopy. All gallbladder specimens were sent for histopathology, irrespective of their gross appearance. Over a period of two years, 220 patients with symptomatic gallstones were admitted for cholecystectomy. Most of the patients were females (88%). Ninety two per cent patients presented with upper abdominal pain of varying duration. All specimens were sent for histopathology. Two hundred and three of the specimens showed evidence chronic cholecystitis, 7 acute cholecystitis with mucocele, 3 acute cholecystitis with empyema and one chronic cholecystitis associated with poly. Six gallbladders (2.8%) showed adenocarcinoma of varying differentiation along with cholelithiasis. The histopathological spectrum of gallbladder is extremely variable. Incidental diagnosis of carcinoma gall bladder is not rare; if the protocol of routine histopathology of all gallbladder specimens is not followed, subclinical malignancies would fail to

  15. Ultrasound evaluation of centenarians' gallbladder. (United States)

    Romano, Marcello; Batticani, Santa; Pistone, Giovanni; Malaguarnera, Mariano


    Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in

  16. Gallbladder and Bile Duct Disorders (United States)

    ... cholesterol) and by-products of drugs from the body. The biliary tract consists of small tubes (ducts) that carry bile from the liver to the gallbladder and then to the small intestine. The gallbladder is a small, pear-shaped sac located beneath the liver. It stores bile. ...

  17. [Uterine cervical carcinoma and human papillomaviruses]. (United States)

    Sugase, M


    For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer.

  18. Side population cells in human gallbladder cancer cell line GBC-SD regulated by TGF-β-induced epithelial-mesenchymal transition. (United States)

    Zhang, Zhifa; Zhu, Feng; Xiao, Ling; Wang, Min; Tian, Rui; Shi, Chengjian; Qin, Renyi


    Mounting evidence has shown that side population (SP) cells are enriched for cancer stem cells (CSCs) responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-β and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-β. In conclusion, TGF-β-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-β-induced EMT may provide a novel strategy for preventing cancer progression.

  19. Indications and recommended approach for surgical intervention of metastatic disease to the gallbladder

    Directory of Open Access Journals (Sweden)

    Khan Zarrish S


    Full Text Available Abstract Metastatic disease to the gallbladder is unusual. The most common malignancy metastatic to the gallbladder is melanoma, followed by renal cell carcinoma (RCC and breast cancer. Due to the unusual nature of the disease, there are no trials available for review. Thus, the management for these patients has been based on institutional experience and review of case series. The indications for surgical intervention for melanoma are metastatic disease discrete to the gallbladder and biliary symptoms, which are uncommon for melanoma, but might occur due to cystic duct obstruction culminating in cholecystitis. Laparoscopic cholecystectomy without a lymphadenectomy is emerging as the preferred approach for this metastatic deposit. The vast majority of patients with metastases to the gallbladder from RCC carry a good prognosis and a laparoscopic cholecystectomy should be considered. Patients with metastases to the gallbladder from the breast classically present with biliary symptoms and commonly undergo a laparoscopic cholecystectomy, which invariably demonstrates a deposit in the gallbladder from lobular breast cancer. In the present report, we review the indications for surgical intervention from various malignancies metastatic to the gallbladder and the current consensus for the laparoscopic approach from the diverse metastatic deposits to the gallbladder.

  20. Evaluation of gallbladder volume and contraction index with three-dimensional ultrasonography in healthy dogs. (United States)

    Rahmani, Vahideh; Molazem, Mohammad; Jamshidi, Shahram; Vali, Yasamin; Hanifeh, Mohsen


    Three-dimensional (3D) ultrasonography has been shown to be an accurate and appropriate tool for measurement of gallbladder volume in humans. Therefore, we applied this novel technique for the first time to study fasting and postprandial gallbladder volume in 10 healthy dogs and compared the results with those of 2-dimensional (2D) ultrasonography. Fasting gallbladder volumes determined by 3D ultrasonography were significantly higher than corresponding volumes determined by 2D ultrasonography (Pultrasonography (Pultrasonography showed no significant difference (P=0.189). The Gallbladder contraction index was higher in 3D ultrasonography than 2D ultrasonography; however, it did not reach statistical significance (P=0.25). In conclusion, 3D ultrasonography was able to measure gallbladder volume in healthy dogs in this study. It is suggested that 3D ultrasonography can be used to accurately estimate gallbladder volume and contractility.

  1. Routine histopathology for carcinoma in cholecystectomy specimens not evidence based: a systematic review

    NARCIS (Netherlands)

    Swank, Hilko A.; Mulder, Irene M.; Hop, Wim C.; van de Vijver, Marc J.; Lange, Johan F.; Bemelman, Willem A.


    Routine histopathological examination of gallbladder specimens is mainly performed to identify unexpected gallbladder carcinoma (GBC). This systematic review assesses the prevalence and characteristics of GBC in cholecystectomy specimens. PubMed, EMBASE, Web of Science, and the Cochrane Library were

  2. Imaging of human urothelial carcinoma samples using multimodal multiphoton microscopy (United States)

    Baria, E.; Barone, A.; Nesi, G.; Pavone, F. S.; Cicchi, R.


    We combined Second Harmonic Generation and Two-Photon Fluorescence for imaging ex vivo tissue sections of human bladder affected by urothelial carcinoma. We studied different grades of the tumor, and compared them to healthy bladder mucosa.

  3. Human papilloma virus prevalence in laryngeal squamous cell carcinoma. (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E


    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  4. Chronic Diarrhea: A Concern After Gallbladder Removal? (United States)

    Chronic diarrhea: A concern after gallbladder removal? I had my gallbladder removed six months ago, and I'm ... Barkun A, et al. Bile acid malabsorption in chronic diarrhea: Pathophysiology and treatment. Canadian Journal of Gastroenterology. 2013; ...

  5. Study of Hartmann’s Pouch of the Gallbladder

    Directory of Open Access Journals (Sweden)

    Laila Farzana Khan


    Full Text Available Background: The gall bladder is a hollow pear shaped sac lying within a fossa on the visceral surface of the right lobe of the liver. In the junction of neck of the gallbladder and the cystic duct, there is a pouch present called Hartman’s pouch or infundibulum of the gallbladder which is a frequent but inconstant feature of the normal gallbladder. It is the common site of lodged gallstones. Objective: To determine the proportion of presence of Hartman’s pouch in our population so that the concerned personnel might have a thought in mind that common pathologies of gall bladder may also involve this pouch. Materials and method: This cross sectional study was carried out in the department of Anatomy, Sir Salimullah Medical College & Mitford Hospital, Dhaka, Bangladesh, from July 2010 to June 2011. The number of sample was 62 postmortem human gallbladders which were collected from unclaimed dead bodies. Results: Hartmann’s pouch of the gallbladder was found in 45 (72.58%. Conclusion: Hartman’s pouch is present in a good proportion of our population.

  6. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)



    Oct 5, 2011 ... from tumour and adjacent normal oral mucosa of patients with OVC and oral squamous cell carcinoma. (OSCC) were separated with two ... node and implant metastasis can be found in infiltrative type and cystoid type ..... according to circadian rhythms in mouse liver (Wei et al.,. 2006). In the latter study, ...

  7. Two incidental cases of abdominal aortic aneurysm and gallbladder cancer. Further data influencing the management of patients affected by aneurysm and gallbladder disease. (United States)

    De Monti, M; Ghilardi, G; Bianchi, E; Kunkl, E; Scorza, R


    Abdominal aortic aneurysm and cholelithiasis are two common diseases in the elderly population. The prevalence of abdominal aortic aneurysms ranges between 1.8 and 6.6% in autoptic series and it's estimated that 2.5% of the over sixty year old population is affected. Carcinoma of the gallbladder is the most common malignant tumor of the biliary tract and in the United States is the fifth most frequent digestive tract malignancy; it's incidence ranges between 2 to 10 cases of 100,000 persons/year. No adequate guidelines are now available to assist the surgeon, in the case of concomitant gallbladder disease and abdominal aortic aneurysm. In this paper the management of abdominal aortic aneurysm in a patient with gallbladder disease is discussed in order to assist the surgeon deciding whether to perform concomitant aneurysm resection and cholecystectomy. In 162 aneurysmectomies (1987-1997) 18 (11.11%) patients underwent combined aneurysmectomy and cholecystectomy operation. The patients ranged in age from 49 to 88 years (average 69 years). In two cases the anatomo-histological specimen examinations (twelve sections) demonstrated a gallbladder carcinoma. The overall mortality rate was 5.56% either for aneurysmectomy alone or for combined therapy. In case of abdominal aortic aneurysm and concomitant gallbladder disease, in choosing simple endoaneurysmectomy, the surgeon has to consider the risk of early and late complications of leaving a diseased gallbladder in place. In case of concomitant performance of both operations, the risks of a possible septic graft contamination must be considered. We believe that the patient may be best served by performing the vascular and nonvascular procedures in the same operation. In this paper a new proof, till now never considered in the international literature, is presented to support our opinion: the possibility of concomitant unknown cancer or precancerous lesions in a lithiasic gallbladder. Diagnosis of these lesions is, indeed

  8. Gallbladder splenosis: a hereto unreported mimicker of a gallbladder neoplasm. (United States)

    Tsai, Leo L; Kaliannan, Krithica; Mortele, Koenraad J


    Splenosis is a completely benign entity that can mimic a primary mass or metastasis. Herein we report the first known case of gallbladder splenosis in a 49-year-old woman with an extensive surgical and medical history. Cross-sectional computed tomography and MRI demonstrated a single mass arising from the gallbladder fundus. Revelation of splenectomy, confirmed to be traumatic from medical records, raised the suspicion for splenosis. The diagnosis was confirmed with a Technecium-99m-labeled heat-damaged blood cell scan, considered the gold-standard for detection of ectopic splenic tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Carcinoma de vesícula biliar mascarado por Síndrome de Mirizzi: relato de caso e revisão da literatura = Carcinoma of the gallbladder masked by Mirizzi Syndrome: case report and literature review

    Directory of Open Access Journals (Sweden)

    Kupske, Abrão


    Conclusões: a concomitância da Síndrome de Mirizzi com carcinoma de vesícula é extremante rara, pois são doenças pouco frequentes. Para o diagnóstico definitivo do tumor de vesícula biliar é sempre imperativo o estudo anatomopatológico de todas as peças cirúrgicas

  10. Determining a Sonographic Nomogram for Gallbladder Spherical ...

    African Journals Online (AJOL)

    Kurtosis and skewness values (0.991 and 0.152 respectively) showed even distribution . This study establishes a normogram for the population using the model formula and could be used in the assessment of gallbladder in conditions giving rise to gallbladder hydrops. Keywords: Sonography, Gallbladder Spherical index, ...

  11. Isolated traumatic rupture of the gallbladder

    Directory of Open Access Journals (Sweden)

    Benjamin Yin Ming Kwan, MD


    Treatment for gallbladder injury is most commonly cholecystectomy. Mortality rates in patients with gallbladder injuries are related to associated injuries, including cardiac, thoracic or intra-abdominal hemorrhage, or multi-organ failure and/or brain damage. In isolated gallbladder injury, the prognosis is good.

  12. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe


    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils....... The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising...


    Directory of Open Access Journals (Sweden)

    Georgi N. Nikolov


    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  14. Gallbladder Agenesis with Refractory Choledocholithiasis

    Directory of Open Access Journals (Sweden)

    Jamie Tjaden


    Full Text Available Congenital agenesis of the gallbladder is a rare anomaly which is usually asymptomatic and found incidentally. In some cases, however, patients are symptomatic. Common symptoms include right upper quadrant abdominal pain, nausea, and vomiting. Jaundice is present in some symptomatic cases and is due to associated choledocholithiasis (Fiaschetti et al. 2009. In this case, a 63-year-old female presents with jaundice and episodic right upper quadrant abdominal pain with nausea and vomiting. Bilirubin and alkaline phosphatase were found to be markedly elevated. Upper endoscopic ultrasound (EUS revealed choledocholithiasis, and the patient required multiple endoscopic retrograde cholangiopancreatography (ERCP sessions before successful extraction of all stones. Subsequent surgical exploration revealed congenital agenesis of the gallbladder. Although this is a rare finding, patients with agenesis of the gallbladder are at increased risk of developing de novo choledocholithiasis which may be challenging to extract.

  15. Quantitative diffusion-weighted MRI parameters and human papillomavirus status in oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Schouten, C.S.; Graaf, P. de; Bloemena, E.; Witte, B.I.; Braakhuis, B.J.; Brakenhoff, R.H.; Leemans, C.R.; Castelijns, J.A.; Bree, R. de


    BACKGROUND AND PURPOSE: Patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus-negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC

  16. Longest gallbladder: A case report

    Directory of Open Access Journals (Sweden)

    Rahul Yadav


    Conclusion: Mucocele of gallbladder present an important hurdle in successful laparoscopic cholecystectomy. A habit of calm and slow dissection with precautions should be developed. Clearance of the calot's triangle with limited use of electro cautery should be done before proceeding towards ligation or clip application to various structures.

  17. Unusual presentation of gallbladder perforation

    Directory of Open Access Journals (Sweden)

    G. Jayasinghe


    Conclusions: Percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis, and may present in a wide variety of locations. Therefore it is imperative to conduct a full body inspection in the septic patient, even when a source has been identified.

  18. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B


    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...

  19. Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

    NARCIS (Netherlands)

    Halmos, Gyorgy B; van der Laan, Tom P; van Hemel, Bettien M; Dikkers, Frederik G; Slagter-Menkema, Lorian; van der Laan, Bernard F A M; Schuuring, Ed

    The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were

  20. Rapid induction of senescence in human cervical carcinoma cells (United States)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong


    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  1. Overexpression of LncRNA-ROR predicts a poor outcome in gallbladder cancer patients and promotes the tumor cells proliferation, migration, and invasion. (United States)

    Wang, Shou-Hua; Zhang, Ming-Di; Wu, Xiao-Cai; Weng, Ming-Zhe; Zhou, Di; Quan, Zhi-Wei


    LncRNA-ROR has been reported to be involved in many kinds of human cancers. However, whether LncRNA-ROR is involved in gallbladder cancer progression remains largely unknown. The objective of this study is to investigate the role of LncRNA-ROR in gallbladder cancer. We found that LncRNA-ROR expression level was upregulated in gallbladder cancer tissues (P ROR was significantly associated with poor prognosis in gallbladder cancer patients (P ROR inhibited cell proliferation, migration, and invasion. The epithelial-mesenchymal transition (EMT) phenotype induced by TGF-β1 was reversed after LncRNA-ROR knocking down in SGC-996 and Noz cells. LncRNA-ROR plays an important role in the development of gallbladder cancer and mediates the EMT in gallbladder cancer. LncRNA-ROR might act as a marker of prognosis and therapeutic target for gallbladder cancer.

  2. Radiofrequency Thermoablation of HCC Larger Than 3 cm and Less Than 5 cm Proximal to the Gallbladder without Gallbladder Isolation: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Antonio Orlacchio


    Full Text Available Radiofrequency ablation (RFA is an effective minimally invasive treatment for nonsurgical hepatocellular carcinoma (HCC, but ablation of tumors close to the gallbladder could be associated with several complications. We report our experience on the treatment of HCC close to the gallbladder with RFA. Eight RFA procedures were performed in eight patients with HCC larger than 3 cm and less than 5 cm close to the gallbladder. In all cases, a percutaneous approach was used. There were no major complications. Only in two patients a minimal wall thickening of the gallbladder was observed. Contrast enhanced computed tomography carried out after 30 days from the first procedure showed complete necrosis in seven patients (87%. Only one patient had local recurrence at 11 months of followup. Although limited, our experience suggests that, after careful preprocedural planning, in experienced hands and with appropriate technology, percutaneous RFA could be safely performed even for lesions larger than 3 cm located in close adjacency to the gallbladder.

  3. Telomerase Activity in Human Ovarian Carcinoma (United States)

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.


    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

  4. Gallbladder Volvulus Presenting as Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Zachary Bauman


    Full Text Available We encountered a case of gallbladder volvulus in an 88-year-old thin female in which the initial presentation was more consistent with that of acute appendicitis. After complete work-up, including physical exam, lab work, and computed tomography, the definite diagnosis of gallbladder volvulus was not made until intraoperative visualization was obtained. Gallbladder volvulus is a rare but serious condition, which requires a high clinical suspicion so prompt surgical intervention can be undertaken.

  5. Nutritional factors in gallbladder diseases

    Directory of Open Access Journals (Sweden)

    Thaiane Prolo


    Full Text Available Biliary system disorders are all diseases that affect the gallbladder and the ducts. They may be originated from various etiologies. Inadequate living habits, being female and smoking are risk factors for the development of these diseases, as well as poor nutrition, nutritional deficiencies, obesity and metabolic syndrome. However, the adequate consumption of fruits and vegetables and the regular practice of physical activity act as protective factors for these diseases.

  6. Gallbladder Polyps: Can They Be Cancerous? (United States)

    ... pain, acute acalculous cholecystitis, cholesterolosis, adenomyomatosis, and gallbladder polyps. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 10th ed. ...

  7. Selective assembly of laminin variants by human carcinoma cells

    DEFF Research Database (Denmark)

    Wewer, U M; Wayner, E A; Hoffstrom, B G


    BACKGROUND: The laminins are heterotrimeric basement membrane glycoproteins. Eight subunits that can be assembled into laminins have been characterized and are known as: A, B1, B2, S, M, K, B2t, B1k laminin chains. Although many neoplastic cells secrete laminins and some of them even assemble...... basement membranes, the pattern of production of various laminin subunits remains to be explored. EXPERIMENTAL DESIGN: The expression of laminin was examined in several human carcinoma cells using a panel of specific cDNA probes as well as polyclonal and chain specific monoclonal antibodies....... For this purpose a human laminin S chain 2 kb cDNA was isolated and characterized and used together with existing probes for laminin chains. RESULTS: All carcinoma cell lines had a high level of expression of three light chains (B1, S and B2) mRNA. In contrast, the heavy chains of laminin, A and M, were expressed...

  8. ORIGINAL ARTICLE Sonographic gallbladder wall thickness in ...

    African Journals Online (AJOL)

    Aim. The aim of the study was to determine the ultrasonic gallbladder wall thickness in normal adult Nigerians so as to create standards for defining gallbladder abnormalities in Nigerians. Method. Four hundred adults comprising 228 (57%) women and 172. (43%) men aged 16 - 78 years, who had normal clinical history ...

  9. ORIGINAL ARTICLE Sonographic gallbladder wall thickness in ...

    African Journals Online (AJOL)

    The study population's age ranged from 16 - 78 years, with a mean age and SD of 32±13.2 years. The age parameter was unevenly distributed. →. →. Fig. 1. Longitudinal US image showing site of measurement of gallbladder wall thickness (arrows). Table I. Age distribution of mean gallbladder wall thickness in the study ...

  10. Isolated gallbladder perforation following blunt abdominal trauma ...

    African Journals Online (AJOL)

    A 32-year-old man sustained an isolated perforation of the gallbladder following blunt abdominal trauma. A preoperative diagnosis was made on an ultrasound scan, which showed a pericholecystic fluid collection only. At laparotomy, a gallbladder perforation at the infundibulum was identified with a localised bile collection, ...

  11. Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision (United States)

    Qiao, Tie; Huang, Wan-Chao; Luo, Xiao-Bing; Zhang, Yang-De


    In recent years, some Chinese doctors have proposed a new concept, gallstone removal without gallbladder excision, along with transition of the medical model. As there is no specialized endoscope for gallstone removal without gallbladder excision, we designed and produced a new series of gallbladder endoscopes and accessories that have already been given a Chinese invention patent (No. ZL200810199041.2). The design of these gallbladder endoscopes was based on the anatomy and physiology of the gallbladder, characteristics of gallbladder disease, ergonomics, and industrial design. This series of gallbladder endoscopes underwent clinical trials in two hospitals appointed by the State Administration of Traditional Chinese Medicine. The clinical trials showed that surgeries of gallstones, gallbladder polyps, and cystic duct calculus could be smoothly performed with these products. In summary, this series of gallbladder endoscopes is safe, reliable, and effective for gallstone removal without gallbladder excision. This note comprehensively introduces the research and design of this series of gallbladder endoscopes.

  12. Postoperative chemoradiotherapy for gallbladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Chie, E.K.; Ha, S.W. [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Seoul National Univ. (Korea, Republic of). Inst. of Radiation Medicine; Jang, J.Y.; Kim, S.W. [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of). Dept. of Surgery; Han, S.W.; Oh, D.Y.; Im, S.A.; Kim, T.Y.; Bang, Y.J. [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of). Dept. of Internal Medicine


    The goal of this work was to analyze the outcome of adjuvant chemoradiotherapy for patients with gallbladder cancer who underwent surgical resection and to identify the prognostic factors for these patients. Between August 1989 and November 2006, 47 patients with gallbladder cancer underwent surgical resection followed by adjuvant radiotherapy. There were 21 males and 26 females, and median age was 60 years (range 44-75 years). Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40-50 Gy at 2 Gy/fraction; 41 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 48 months for survivors. There were 2 isolated locoregional recurrences, 14 isolated distant metastases, and 7 combined locoregional and distant relapses. The 5-year overall survival rate was 43.7%. According to the extent of resection, the 5-year overall survival rates were 52.8%, 20.0%, and 0% in R0-, R1-, and R2-resected patients, respectively (p = 0.0038). On multivariate analysis incorporating extent of resection, T stage, N stage, performance of lymph node dissection, and histologic differentiation, extent of resection was the only prognostic factor associated with overall survival (p = 0.0075). Among the 37 patients with R0 resection, there was no difference of 5-year overall survival rates in patients with N0, N1, and Nx diseases (46.2%, 60.0%, and 44.4%, respectively, p = 0.6246). As for significant treatment-related morbidity, there was only 1 patient with grade 4 gastric ulcer. Adjuvant chemoradiotherapy after R0 resection can achieve a good long-term survival rate in gallbladder cancer patients, even in those with lymph node metastases, and may play a role for patients who underwent R0 resection of primary tumor without lymph node dissection. (orig.)

  13. Gallbladder Tuberculosis: CT Findings with Histopathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiu Fang; Yu, Ri Sheng; Qiu, Ling Ling; Dong, Fei; Chen, Ying [Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Shen, Jian [Zhejiang Medical College, Hangzhou (China)


    We wanted to describe the computed tomography (CT) findings of gallbladder tuberculosis (TB) and to correlate them with pathologic findings. There were seven patients (M:F = 3:4: mean age, 46.3 years: age range, 32 to 78 years) in whom gallbladder TB was eventually diagnosed. All of them underwent cross-sectional imaging with CT, a pathologic examination and a retrospective review. CT imaging evaluation was done in each case, including the findings of a mass versus nodule, wall thickening (uniform or irregular) and the enhancement patterns (homogeneous or heterogeneous). All the cases of gallbladder TB revealed the following three different CT findings: micronodular lesion of the gallbladder wall (n = 1), a thickened wall (n = 4) and a gallbladder mass (n = 2). There were three cases of homogeneous enhancement of the lesions, including homogeneous enhancement with nodular lesion, homogeneous uniform thickness enhancement and homogeneous thickness enhancement in one case each, and these cases pathology showed tuberculous granuloma with a little caseating necrosis in one case and tuberculous granuloma with rich fibrous tissue, but little or no evident caseating necrosis in two cases. Four cases of heterogeneous enhancement of the lesions, including heterogeneous uniform-thickness enhancement in two cases, heterogeneous enhancement with a local mass lesion in one case and heterogeneous enhancement with a mass that replaced the gallbladder in one case: in these cases, pathology showed tuberculous granuloma with marked caseation or lique faction necrosis in three cases and tuberculous granuloma by fibrous and calcifi cations accompanied by caseating necrosis in one case. Among the seven cases of gallbladder TB, six cases were accompanied by abdominal extra-gallbladder TB, including abdominal lymph node TB in five cases and hepatic TB in four cases. Gallbladder TB has various CT manifestations, and the enhanced CT findings are well matched with pathological features. An

  14. Sequential changes of attenuation values of bile duct and gallbladder on CT after oral contrast ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Hee; Suh, Chang Hae; Lim, Myung Kwan; Chung, Won Kyun [Inha University College of Medicine, Sungnam (Korea, Republic of)


    8, 3, 2, 5 cases in duodenum. Contrast-filled cystic duct and duodenum were noted in 24 cases and 19 cases respectively on CT scans after fat meal. The CT attenuation values of gallbladder were increased in sequential periods of time and the difference of density of gallbladder between 3 hours and 6 hours was statistically significant ({rho} = 0.0001). The CT attenuation values of gallbladder at 6 hours were heigher than that in 3 hours, statistically. Opacified gallbladder were noted in 2 cases of fatty liver (n = 2), 1 cases of alcoholic liver disease (n = 1), in 1 cases of liver cirrhosis (n = 1). Patients of gallbladder stone (n = 2) or hepatocellular carcinoma (n = 2) had non-opacified gallbladder on CT scans. The CT scans after oral contrast ingestion can show the morphological and functional aspects of gallbladder better than conventional oral cholecystography and can also show biliary trees and other surrounding structures, so it is helpful method for assessment of not only gallbladder disease but also other hepatobiliary diseases.

  15. Micronuclei with kinetochores in human melanoma cells and rectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Weissenborn, U.; Streffer, C. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Inst. fuer Medizinische Strahlenbiologie)


    Micronucleus frequencies were analysed in an X-irradiated human melanoma cell line and in untreated rectal carcinoma cells. As a special aspect of the micronucleus formation, micronuclei-containing kinetochores were analysed by the method of indirect immunofluorescence. The incidence of kinetochore-positive micronuclei was taken as a measure of chromosome loss. The authors have attempted to summarize the data by means of a numerical expression which takes into account the relation between lost chromosomes, visible as kinetochore-positive micronuclei, and the total sum of micronuclei. (author).

  16. Elevated expression of squamous cell carcinoma antigen (SCCA is associated with human breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Joseph M Catanzaro

    Full Text Available Squamous cell carcinoma antigen (SCCA belongs to the serine protease inhibitor (Serpin family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360 and normal breast epithelium (n = 124. SCCA expression was scored on a tiered scale (0-3 independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%, Grade II (2.5%, and Grade III (9.4% breast cancers (p<0.0001. Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005. No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124. SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR double-negative tumors (p = 0.0009. Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively. This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.

  17. Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hagmann, Wolfgang, E-mail:; Faissner, Ralf [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Schnolzer, Martina [Functional Proteome Analysis, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Lohr, Matthias [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Department of Surgical Gastroenterology, CLINTEC, K53, Karolinska Institute, SE-14186 Stockholm (Sweden); Jesnowski, Ralf [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Department of Medicine II, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany)


    Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil.

  18. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma. (United States)

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang


    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  19. Heterotopic pancreatic tissue in gallbladder

    Directory of Open Access Journals (Sweden)

    Aylhin Joana Lopez Marcano


    Full Text Available The heterotopic pancreas (PH is the atypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas. PH is a rare condition that can be observed at any level of the gastrointestinal tract and even in other organs. Histopathological characterization of PH allows surgeons to distinguish it from other lesions. Although it is usually a benign and asymptomatic disease, it can occasionally cause complications (obstruction, hemorrhage, inflammation, or malignant transformation. In conclusion, localization in the gallbladder in the few cases of PH is very rare. We present two cases in which, after cholecystectomy indicated by other causes, in the pathological study of the surgical specimen, type 2 pancreatic tissue was found according to the Heinrich classification. [Arch Clin Exp Surg 2016; 5(4.000: 250-253

  20. Gallbladder Cancer Incidence and Death Rates (United States)

    ... Cancer Conference Stay Informed Gallbladder Cancer Incidence and Death Rates Recommend on Facebook Tweet Share Compartir Quick ... a late stage with a poor outcome, often death. The journal Cancer Epidemiology, Biomarkers and Prevention published ...

  1. Beware the left-sided gallbladder

    African Journals Online (AJOL)

    %, and is defined as a gallbladder located to the left of the ligamentum teres and the falciform ligament.1 LSGB was first described by Hochstetter in 1886, and its identification is important because of the numerous and potentially hazardous.

  2. [Reimplantation of the gallbladder. Indications and results]. (United States)

    Milani, R; Di Franco, S; Impagliazzo, A


    There is no good reason why a gallbladder that has been compressed and displaced by a parasitic or malformative cyst, but is otherwise free of anatomical or irreversible lesions, should be irrevocably sacrificed. Treatment of the primary lesion can thus be followed by re-implantation of the gallbladder. The indications for this surgical technique and its limitations are described with reference to a personal series.

  3. Torsion of Wandering Gallbladder following Colonoscopy

    Directory of Open Access Journals (Sweden)

    Sean R. Warfe


    Full Text Available Torsion of the gallbladder is an uncommon condition that may present as an acute abdomen. Its preoperative diagnosis can often be challenging due to its variable presentation, with specific sonographic signs seen infrequently. We describe, to our knowledge, the first case of torsion of a wandering gallbladder following a colonoscopy in a 69-year-old female who presented with acute abdominal pain after procedure. This was discovered intraoperatively, and after a subsequent cholecystectomy, she had an uncomplicated recovery.

  4. The systematic classification of gallbladder stones.

    Directory of Open Access Journals (Sweden)

    Tie Qiao

    Full Text Available BACKGROUND: To develop a method for systematic classification of gallbladder stones, analyze the clinical characteristics of each type of stone and provide a theoretical basis for the study of the formation mechanism of different types of gallbladder stones. METHODOLOGY: A total of 807 consecutive patients with gallbladder stones were enrolled and their gallstones were studied. The material composition of gallbladder stones was analyzed using Fourier Transform Infrared spectroscopy and the distribution and microstructure of material components was observed with Scanning Electron Microscopy. The composition and distribution of elements were analyzed by an X-ray energy spectrometer. Gallbladder stones were classified accordingly, and then, gender, age, medical history and BMI of patients with each type of stone were analyzed. PRINCIPAL FINDINGS: Gallbladder stones were classified into 8 types and more than ten subtypes, including cholesterol stones (297, pigment stones (217, calcium carbonate stones (139, phosphate stones (12, calcium stearate stones (9, protein stones (3, cystine stones (1 and mixed stones (129. Mixed stones were those stones with two or more than two kinds of material components and the content of each component was similar. A total of 11 subtypes of mixed stones were found in this study. Patients with cholesterol stones were mainly female between the ages of 30 and 50, with higher BMI and shorter medical history than patients with pigment stones (P<0.05, however, patients with pigment, calcium carbonate, phosphate stones were mainly male between the ages of 40 and 60. CONCLUSION: The systematic classification of gallbladder stones indicates that different types of stones have different characteristics in terms of the microstructure, elemental composition and distribution, providing an important basis for the mechanistic study of gallbladder stones.

  5. [Gallbladder volvulus: Diagnostic and surgical challenges]. (United States)

    Abadía-Barnó, Pedro; Coll-Sastre, Magdalena; Picón-Serrano, Carmen; Sanjuanbenito-Dehesa, Alfonso; Cabañas-Montero, Jacobo


    The gallbladder volvulus is defined as the rotation of the gallbladder on its mesentery along the axis of the cystic duct and cystic artery. It is an extremely rare surgical disease and definitive diagnosis is usually made during surgery. A 78 year old woman presented with upper right quadrant abdominal pain, with no comorbidities and no other accompanying symptoms. Analysis revealed haemodynamic instability and leukocytosis. Computed tomography of abdomen showed an acute cholecystitis. During emergency right hypochondrium laparotomy, the gallbladder was found to be twisted counterclockwise with huge gangrenous gallbladder distal. Open cholecystectomy was performed and after the surgery, the patient was discharged in a few days. Gallbladder volvulus, or gallbladder torsion, is a rare condition and should be considered when clinical and imaging findings of complicated cholecystitis are present. The performance of urgent laparoscopic surgery would be first option to avoid perforation, peritonitis and haemodynamic instability. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  6. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane. (United States)

    Saghravanian, Nasrollah; Ghazi, Narges; Meshkat, Zahra; Mohtasham, Nooshin


    Squamous cell carcinoma (SCC) is the most common oral malignancy, and verrucous carcinoma (VC) is a less invasive type of SCC. Leukoplakia (LP) is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV) has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR) has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions. One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs) and 18 normal mucosa samples (as a control group) were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction. The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%), we observed the presence of HPV HR (types 16 and 18). All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230). Additionally, 15 (13.1%) SCCs showed HPV positivity, but this was not significant (p=0.830). The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11). A statistically significant association was not observed between HPV and SCC or VC in the oral cavity. More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  7. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian


    Full Text Available Objectives: Squamous cell carcinoma (SCC is the most common oral malignancy, and verrucous carcinoma (VC is a less invasive type of SCC. Leukoplakia (LP is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions.  Methods: One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs and 18 normal mucosa samples (as a control group were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction.  Results: The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%, we observed the presence of HPV HR (types 16 and 18. All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230. Additionally, 15 (13.1% SCCs showed HPV positivity, but this was not significant (p=0.830. The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11. A statistically significant association was not observed between HPV and SCC or VC in the oral cavity.  Conclusions: More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  8. [Gallbladder polypoid lesions. Three clinical cases with difficult diagnosis and literature review]. (United States)

    Spaziani, E; Petrozza, V; Di Filippo, A; Picchio, M; Ceci, F; Miraglia, A; Moretti, V; Briganti, M; Greco, E; Pattaro, G; De Angelis, F; Salvadori, C; Stagnitti, F


    Gallbladder polypoid lesions occur in 1.3%-6.9% of cases. The preoperative diagnosis between benign, malignant and potentially malignant lesions is difficult. Therefore it is not possible any. The Authors describe three cases. The case 1 was a gallbladder diffuse adenomyomatosis; the ultrasound and the CT were of little help in defining preoperatively the nature and the gravity of the thickening. Case 2 was an adenomyomatosis of the fundus: the ultrasound examinations were not able to establish preoperatively lesion's nature, site and dimensions. In the case 3, ultrasounds showed polypoid lesions and calculi concrections not found in colecistectomy. The ultrasound is the most widely used diagnostic tool in the evaluation of gallbladder polypoid lesions; its accuracy is only 66%. CT, which has an accuracy level of 75%, must be carried out there is any possibility of malignant degeneration of the polyp. If doubts persist, a MR, 93% accuracy, is indicated. In selected cases, PET can be of further help. The preoperative diagnosis of the nature of gallbladder polypoid lesions is "difficult" and this justifies the lack of consensus on treatment. However, the adenoma-carcinoma sequence, widely discussed in literature, can justifies to the use of CT, MR, PET and surgical treatment after an ultrasound examination.

  9. Gallbladder cancer: South American experience. (United States)

    Arroyo, Gerardo F; Gentile, Alberto; Parada, Luis A


    Large differences in terms of incidence and mortality due to gallbladder cancer (GBC) have been reported worldwide. Moreover, it seems that GBC has unique characteristics in South America. We surveyed the literature looking for information about the epidemiology, basic and translational research, and clinical trials performed in South America in order to critically analyze the magnitude of this health problem in the region. Compared to other geographic areas, age-standardized mortality rates (ASMR) for GBC in women are very high, particularly in many western areas of South America. Genetic, as well as dietary and environmental factors likely contribute to the pathogenesis of this disease in the area. Compared to other regions the profile of abnormalities of key genes such as KRAS and TP53 in GBC seems to slightly differ in South America, while the clinical behavior appears to be similar with a median overall survival (OS) of 6.5 to 8 months in advanced GBC. In contrast to Europe and USA, prophylactic cholecystectomy is a common practice in western areas of South America. GBC particularly affects women in South America, and represents a significant public health problem. It appears to have peculiarities that pose an urgent need for additional research aimed to discover risk factors, molecular events associated with its development and new treatment options for this lethal disease.

  10. Heterotopic pancreas presenting as suspicious mass in the gallbladder. (United States)

    Foucault, Amélie; Veilleux, Hubert; Martel, Guillaume; Lapointe, Réal; Vandenbroucke-Menu, Franck


    Heterotopic pancreas is a rare entity. Thirty-three cases in the gallbladder have been reported. We describe the first case of heterotopic pancreas mimicking a gallbladder cancer, identified within a calcified lesion in the thickened posterior wall of the gallbladder. A 72-year-old woman with right upper quadrant pain was referred with a suspicion of gallbladder neoplasia. A CT scan demonstrated a 1 cm thickened posterior wall of the gallbladder with a 2 mm punctate calcification. An open cholecystectomy was carried out without complication. The frozen section demonstrated pancreatic tissue. Heterotopic pancreas of the gallbladder is highly uncommon. It can mimic a neoplastic process in the gallbladder, particularly in the context of calcification. Its malignant potential in the gallbladder is unknown, in contrast to previously described neoplastic transformation with gastric heterotopic pancreas.

  11. Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Belghmi Khalid


    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. There's is evidence that Epstein Barr virus (EBV is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV and NPC. Method Seventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59. Results The age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9% were classified as type 3 (undifferentiated carcinoma, 6 (8.6% as type 2 (non keratinizing NPC and only 2 (2.9% cases were classified as type 1 (keratinizing NPC. EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70. Molecular analysis showed that 20.8% (5/24 were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45. In addition, statistical analysis showed that there's no association between sex or age and HPV infection (P > 0.1. Conclusion Our data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.

  12. Torsion of the gallbladder: a case report

    Directory of Open Access Journals (Sweden)

    Ijaz Samia


    Full Text Available Abstract Introduction Torsion of the gallbladder is a rare condition that most commonly affects the elderly. Pre-operative diagnosis is the exception rather than the rule. Any delay in treatment can be fatal as the gallbladder may rupture, leading to biliary peritonitis. Case presentation We present the case of an 80-year-old woman who was admitted with right upper quadrant pain initially thought to be secondary to acute cholecystitis. Subsequent ultrasound and computed tomography scans of the abdomen revealed signs suggestive of acute cholecystitis but neither modality detected any gallstones. As the patient's symptoms failed to resolve on conservative management, she was taken to theatre for an open cholecystectomy. Intra-operatively, the gallbladder had undergone complete torsion and appeared gangrenous. A routine cholecystectomy followed and she recovered from the operation without incident. Conclusion It is rare to diagnose torsion of the gallbladder pre-operatively despite advances in diagnostic imaging. However, this differential diagnosis should be borne in mind particularly in the elderly patient, without proven gallstones, who fails to improve on conservative management. An emergency cholecystectomy is indicated in the event of diagnosing torsion of the gallbladder to avert the potentially lethal sequelae of biliary peritonitis.

  13. Torsion of the gallbladder: a case report. (United States)

    Ijaz, Samia; Sritharan, Kaji; Russell, Neil; Dar, Manzoor; Bhatti, Tahir; Ormiston, Michael


    Torsion of the gallbladder is a rare condition that most commonly affects the elderly. Pre-operative diagnosis is the exception rather than the rule. Any delay in treatment can be fatal as the gallbladder may rupture, leading to biliary peritonitis. We present the case of an 80-year-old woman who was admitted with right upper quadrant pain initially thought to be secondary to acute cholecystitis. Subsequent ultrasound and computed tomography scans of the abdomen revealed signs suggestive of acute cholecystitis but neither modality detected any gallstones. As the patient's symptoms failed to resolve on conservative management, she was taken to theatre for an open cholecystectomy. Intra-operatively, the gallbladder had undergone complete torsion and appeared gangrenous. A routine cholecystectomy followed and she recovered from the operation without incident. It is rare to diagnose torsion of the gallbladder pre-operatively despite advances in diagnostic imaging. However, this differential diagnosis should be borne in mind particularly in the elderly patient, without proven gallstones, who fails to improve on conservative management. An emergency cholecystectomy is indicated in the event of diagnosing torsion of the gallbladder to avert the potentially lethal sequelae of biliary peritonitis.

  14. Tissue Factor and Tissue Factor Pathway Inhibitor in Chronically Inflamed Gallbladder Mucosa

    Directory of Open Access Journals (Sweden)

    Jacek Liczko


    Full Text Available We characterised a tissue factor (TF and tissue factor pathway inhibitor (TFPI expression in relation to severity of inflammatory infiltration of the gallbladder mucosa in a chronic cholecystitis. We prospectively studied the gallbladder specimens obtained from 54 patients who had undergone cholecystectomy due to chronic calculous cholecystitis and 16 calculosis-free gallbladder specimens obtained from patients who underwent cholecystectomy due to the polyp/polyps as well as in cases of gallbladder injury. To assess TF and TFPI immunoreactivity by immunohistochemistry, the monoclonal anti-human TF and TFPI antibodies were used. The inflammatory infiltration of the gallbladder mucosa was reflected by the number of CD3 and CD68 positive cells. The expression of TF and TFPI differed significantly between the cholecystitis and the control group. Most capillary endothelial cells of the cholecystitis group presented weak expression for TFPI. The mean number of CD3 positive lymphocytes in the cholecystitis group was 18.6 ± 12.2, but the mean number of CD68 positive cells was 29.7 ± 13.9. In the control sections, it was 3.1 ± 1.9 and 8.8 ± 3.9, respectively (P<0.001. The results of the current study suggest that the tissue procoagulant state found may be engaged in the etiopathogenesis of the cholecystitis.

  15. The case for aflatoxins in the causal chain of gallbladder cancer. (United States)

    Foerster, Claudia; Koshiol, Jill; Guerrero, Ariel R; Kogan, Marcelo J; Ferreccio, Catterina


    Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR=18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio=13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR=4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Peptic ulcer in the gallbladder. A case report

    DEFF Research Database (Denmark)

    Larsen, E H; Diederich, P J; Sørensen, Flemming Brandt


    Gastric mucosa can be found in the gallbladder as a congenital heterotopia. A case of a perforated peptic ulcer in the gallbladder with concomitant hemorrhage in heterotopic gastric mucosa causing hematemesis and melena is presented.......Gastric mucosa can be found in the gallbladder as a congenital heterotopia. A case of a perforated peptic ulcer in the gallbladder with concomitant hemorrhage in heterotopic gastric mucosa causing hematemesis and melena is presented....

  17. A Rare Complication of Cholecystitis Diagnosed by Ultrasonography: Gallbladder Perforation

    Directory of Open Access Journals (Sweden)

    Tarkan Ergun


    Gallbladder perforation is a rare but severe complication of acute cholecystitis with a high morbidity and mortality. Clinical symptoms of gallbladder perforation are usually unspecific, and the differentiation from uncomplicated cholecystitis can be challenging. Early diagnosis of gallbladder perforation and immediate surgical intervention are of crucial importance and might reduce mortality rates and prolonged postoperative hospital stays. We present a case of gallbladder perforation in a 59-year-old man with preoperatively diagnosed by ultrasonography.

  18. Gallbladder mucocele in a 12-year-old cocker spaniel. (United States)

    Norwich, Alison


    A 12-year-old, spayed cocker spaniel was presented for panting behavior which had increased over the past several months. A diagnosis of hyperadrenocorticism was made, and ultrasound imaging revealed the presence of a gallbladder mucocele. While often an incidental finding, gallbladder mucoceles can have consequences and require intervention. The etiology, diagnosis, and management of gallbladder mucoceles are discussed.

  19. Gallbladder mucocele in a 12-year-old cocker spaniel


    Norwich, Alison


    A 12-year-old, spayed cocker spaniel was presented for panting behavior which had increased over the past several months. A diagnosis of hyperadrenocorticism was made, and ultrasound imaging revealed the presence of a gallbladder mucocele. While often an incidental finding, gallbladder mucoceles can have consequences and require intervention. The etiology, diagnosis, and management of gallbladder mucoceles are discussed.

  20. Variabilities of gallbladder contraction indices and a simple ...

    African Journals Online (AJOL)

    Introduction: The objective of this study was to assess the variabilities of gallbladder contraction indices (GBCI) and derive a predictive model for gallbladder and gastric motility. Methods: The gallbladder volume and gastric antral measurements were obtained from 24 healthy male volunteers in preprandial and post-milk ...

  1. Isolated gallbladder rupture following blunt abdominal trauma | Gali ...

    African Journals Online (AJOL)

    The gallbladder is a relatively well‑protected organ; consequently its rupture following blunt abdominal injury is rare and usually associated with other visceral injuries. Isolated gallbladder rupture is extremely rare. We report a healthy Nigerian adult male who sustained isolated gallbladder rupture following blunt abdominal ...

  2. Management of Adult Choledochal Cyst Coexisting with Gallbladder ...

    African Journals Online (AJOL)

    Type IV choledochal cyst and a distended gallbladder with thickened walls containing a heterogeneous .... Figure 8: Photomicrography showing tumor infiltration of the entire wall of the gallbladder. [Downloaded free from ... The aim of treating adult patients with choledochal cyst coexisting with gallbladder cancer is to ...

  3. Gallbladder papillary neoplasms share pathological features with intraductal papillary neoplasm of the bile duct. (United States)

    Wan, Xueshuai; Shi, Jie; Wang, Anqiang; Xie, Yuan; Yang, Xiaobo; Zhu, Chengpei; Zhang, Haohai; Wu, Liangcai; Wang, Shanshan; Huang, Hanchun; Lin, Jianzhen; Zheng, Yongchang; Liang, Zhiyong; Sang, Xinting; Zhao, Haitao


    Intraductal papillary neoplasm of the bile duct (IPNB) has been widely recognized. However, the knowledge of intracystic papillary neoplasm of the gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well defined. In this study, we compared the clinicopathological and immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low-high grade dysplasia) exhibited an earlier onset age, smaller tumor size and lower level of CK20 expression compared to IPNG-2 (invasive carcinoma). Histologically, pancreaticobiliary and intestinal subtype accounted for nearly half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively. Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly expressed in the intestinal subtype than in other subtypes. CK20 expression increased in parallel with tumor progression. In addition, 53.1% of IPNG cases and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant survival advantages to conventional gallbladder adenocarcinoma and cholangiocarcinoma, respectively. In conclusion, papillary adenoma and adenocarcinoma of the gallbladder can be recognized as different pathological stages of IPNG, and they share pathological features with IPNB.

  4. [Macro-microscopic comparative study of gallbladder lesions in La Plata (Argentina)]. (United States)

    Corrons, F J; Sidoti Hartmann, A N; Castelletto, R H


    The histogenesis of the gallbladder carcinoma is under controversy Some authors emphasize the polyp-cancer sequence, whereas others relate the adenocarcinoma with metaplastic and dysplastic changes. It is important to examine immediately the characteristics of the mucosa, in order for guidance to the surgeon at the operating room. With the purpose of correlating the macro-microscopic findings of gallbladder lesions, we studied 306 gallbladder specimens extended and fixed in formaline. We considered: Age, sex, lithiasis, dimensions of the specimens and macroscopic patterns of the mucosal surface. Longitudinal samples were taken for histological examination. Two hundred and thirty seven cases corresponded to female sex (77.4%) and 69 to male sex (22.5%) with an average age of 44 years. Among the microscopic findings, we found gastric metaplasia in 43% of the cases, intestinal metaplasia in 10.8%, low grade dysplasia in 11.8% and high grade dysplasia in 1.6%, and 2 cases of clinically unsuspected invasive carcinomas (0.6%). An association between chronic colecistitis, lithiasis and epithelial changes was confirmed, but the relation between each one of the macroscopic patterns proposed and the histological findings is statistically significant only in the cases of atrophy, probably owing to the overlapping of microscopic findings in the different macroscopic patterns.

  5. Arachidonate metabolism in bovine gallbladder muscle

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, M.; Hidaka, T.; Ueta, T.; Ogura, R.


    Incubation of (1-/sup 14/C)arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of (1-/sup 14/C)PGH2 was virtually identical to that of (1-/sup 14/C)AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.

  6. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection. (United States)

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi


    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis.

  7. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    National Research Council Canada - National Science Library

    Skipper, Anthony; Sims, Jennifer N; Yedjou, Clement G; Tchounwou, Paul B


    ... mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG₂) cells...

  8. Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ

    DEFF Research Database (Denmark)

    Junge, Jette; Poulsen, H; Horn, T


    Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ were morphologically investigated. Lesions were classified according to WHO (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et al. (1991) (warty, basaloid, combined warty/basaloid or bas...

  9. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie


    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  10. Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma. (United States)

    Deng, Lu; Gao, Yiping; Li, Xiao; Cai, Mingbo; Wang, Huimin; Zhuang, Huiyu; Tan, Mingzi; Liu, Shuice; Hao, Yingying; Lin, Bei


    It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What's more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma. The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining. ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p endometrial carcinoma (p endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.

  11. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation


    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel


    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repre...

  12. Gallbladder Boundary Segmentation from Ultrasound Images Using Active Contour Model (United States)

    Ciecholewski, Marcin

    Extracting the shape of the gallbladder from an ultrasonography (US) image allows superfluous information which is immaterial in the diagnostic process to be eliminated. In this project an active contour model was used to extract the shape of the gallbladder, both for cases free of lesions, and for those showing specific disease units, namely: lithiasis, polyps and changes in the shape of the organ, such as folds or turns of the gallbladder. The approximate shape of the gallbladder was found by applying the motion equation model. The tests conducted have shown that for the 220 US images of the gallbladder, the area error rate (AER) amounted to 18.15%.

  13. Local Anesthetics Inhibit the Growth of Human Hepatocellular Carcinoma Cells. (United States)

    Le Gac, Grégoire; Angenard, Gaëlle; Clément, Bruno; Laviolle, Bruno; Coulouarn, Cédric; Beloeil, Hélène


    Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells. The effects of 2 LAs (lidocaine and ropivacaine) (10 to 10 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes. We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10 M [P lidocaine and 59% [P Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01). The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle-related genes that result in a cytostatic effect and induction of apoptosis.

  14. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan. (United States)

    Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu


    Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. GAGE12 mediates human gastric carcinoma growth and metastasis. (United States)

    Lee, Eun Kyung; Song, Kyung-A; Chae, Ji-Hye; Kim, Kyoung-Mee; Kim, Seok-Hyung; Kang, Myung-Soo


    The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes. © 2014 UICC.

  16. Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization. (United States)

    Ahmad, Usama; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees; Siddiqui, Sahabjada


    Nanoemulsion of silymarin was developed and optimized. Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8% v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were used as oil phase, surfactant and co-surfactant while distilled water (65.22% v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of particle size, viscosity, electrical conductivity and refractive index. Further, in vitro release, in vivo pharmacokinetic study, stability study and cancer cell line studies were also performed. The optimized formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also showed higher AUC (p  .05). The cancer cell line studies also confirmed that silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation (p nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.

  17. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. (United States)

    Nault, Jean-Charles; Datta, Shalini; Imbeaud, Sandrine; Franconi, Andrea; Mallet, Maxime; Couchy, Gabrielle; Letouzé, Eric; Pilati, Camilla; Verret, Benjamin; Blanc, Jean-Frédéric; Balabaud, Charles; Calderaro, Julien; Laurent, Alexis; Letexier, Mélanie; Bioulac-Sage, Paulette; Calvo, Fabien; Zucman-Rossi, Jessica


    Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.

  18. Induction of retinoic acid receptor β mediates growth inhibition in retinoid resistant human colon carcinoma cells


    Nicke, B; Riecken, E; Rosewicz, S


    BACKGROUND—The molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood.
AIM—To identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells.
METHODS—Anchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression was evalu...

  19. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells. (United States)

    Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Siddiqui, Maqsood A; Ali, Bahy A


    Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells. A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P hepatocellular carcinoma cells exposed to arsenic trioxide. The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

  20. High-risk human papillomavirus in esophageal squamous cell carcinoma. (United States)

    Antonsson, Annika; Nancarrow, Derek J; Brown, Ian S; Green, Adele C; Drew, Paul A; Watson, David I; Hayward, Nicholas K; Whiteman, David C


    Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16(INK4a) status was assessed by immunohistochemistry. Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16(INK4a). None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors. These findings suggest a very low prevalence of HPV DNA in human ESCC. HPV is very unlikely to be a common cause of ESCC in Australia. (c)2010 AACR.

  1. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection. (United States)

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio


    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  2. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1. (United States)

    Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K


    Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions.

  3. Dynamic protein interaction modules in human hepatocellular carcinoma progression. (United States)

    Yu, Hui; Lin, Chen-Ching; Li, Yuan-Yuan; Zhao, Zhongming


    Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases

  4. Isolated gallbladder rupture following blunt abdominal injury

    African Journals Online (AJOL)


    May 26, 2015 ... A retrospective review consisting of. 1449 patients reported the incidence around 0.067%.[3]. Here, we presented a case of isolated gallbladder rupture following a blunt abdominal injury. Case Report. A 39‑year‑old man with history of cholelithiasis, alcoholism‑related liver cirrhosis, and chronic pancreatitis.

  5. Congenital Duplex Gallbladder Anomaly Presenting as Gangrenous ...

    African Journals Online (AJOL)

    Conclusion: An extensive internet literature search did not reveal any previously described case. This could be the first such case described in the world literature. Though rare, congenital anomalies of the gallbladder must be known to surgeons as they can present unexpectedly and pose diagnostic and operative surgical ...

  6. Association of Aflatoxin and Gallbladder Cancer

    DEFF Research Database (Denmark)

    Koshiol, Jill; Gao, Yu-Tang; Dean, Michael


    from the Shanghai Biliary Tract Cancer case-control study, conducted from 1997 through 2001. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs and the population-attributable fraction for 209 patients with gallbladder cancer and gallstones vs 250 patients with gallstones without cancer...

  7. Type 1 free perforation of the gallbladder.


    Harland, C; Mayberry, J F; Toghill, P. J.


    A series of 4 cases of free perforation of the gallbladder into the peritoneal cavity associated with peritonitis are reported. Two were diagnosed at laparotomy and 2 at post-mortem. The 3 patients who died were men who were either elderly or had serous concomitant diseases, including diabetes, atherosclerosis or alcoholism. The sole survivor was a fit young woman.

  8. Isolated gallbladder rupture following blunt abdominal trauma

    African Journals Online (AJOL)


    Nov 3, 2011 ... with another, direct blow with parts of the motor cycle to the abdomen may be the cause as there were only bruises in the left hypochondrium that led to the earlier suspicion of splenic injury. Several types of GB injuries may result from blunt abdominal trauma. Blunt gallbladder injuries are classified as ...

  9. Determinants of gallbladder kinetics in obesity

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M. H.; van Ierland-van Leeuwen, M. L.; Terpstra, A.


    Obese subjects are at risk of developing gallstones both by being overweight and by reducing their body weight. The aim of the present study was to investigate factors related to disturbances in gallbladder emptying measured by ultrasound. Detailed information about weight loss attempts, age at

  10. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt


    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  11. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma

    DEFF Research Database (Denmark)

    Porter, Sarah; Span, Paul N; Sweep, Fred C G J


    We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup...... of ADAMTSs, based on functional and amino acid sequence similarity (ADAMTS1, 4, 5, 8 and 15), to be the focus of further study in breast carcinoma. Further RNA expression analysis by real-time PCR on a different cohort of 229 patients with breast cancer has identified ADAMTS8 as a predictor of poor overall...... breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients...

  12. Griffonia simplicifolia agglutinin-2-binding glycoprotein as a novel carbohydrate antigen of human colonic carcinoma. (United States)

    Nakayama, J; Okano, A; Maeda, H; Miyachi, M; Ota, H; Katsuyama, T; Kanai, M


    Griffonia simplicifolia agglutinin-2-binding glycoprotein (GBG) in human colonic carcinoma was examined immunochemically and histochemically, GBG was extracted from colonic carcinoma as a serum-type glycoprotein of 160 kilodaltons. GBG was not identical with carcinoembryonic antigen (CEA), since its molecular weight and localization in tissue sections were different from those of CEA. The non-reducing terminals of GBG probably carry N-acetylglucosamine, but not blood group determinants. Furthermore, GBG was released by phosphatidylinositol-specific phospholipase C from cell membrane. GBG was suggested to be anchored to the membrane via linkage to a glycosyl-phosphatidylinositol molecule. Among colonic carcinoma-associated antigens, serum-type glycoproteins having N-acetylglucosamine at non-reducing terminals have not previously been reported. GBG is a novel carbohydrate antigen of human colonic carcinoma.

  13. Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies.


    Watanabe, K.; Sasano, H.; Harada, N.; Ozaki, M.; Niikura, H.; Sato, S.; Yajima, A.


    The expression of P450 aromatase and other steroidogenic enzymes were evaluated in 42 endometrioid endometrial carcinomas, 23 endometrial hyperplasias, and 7 normal endometrial specimens. These findings were correlated with clinicopathological findings to elucidate the possible biological significance of in situ estrogen production in the development of human endometrial carcinoma. Only weak aromatase immunoreactivity was observed in vascular walls and myometrial cells. In contrast, strong ar...

  14. Human papillomavirus-driven neck lymph node metastases from oropharyngeal or unknown primary squamous cell carcinoma


    Schroeder, Lea


    Patients with neck squamous cell carcinoma from unknown primary tumor (NSCCUP) present with lymph node metastases without evidence for a primary tumor. Most patients undergo an aggressive multimodal treatment, which induces severe toxicity. Primary tumors of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers f...

  15. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri


    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  16. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States. (United States)

    Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi


    Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P carcinoma in the United States and is associated with a distinct clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater. (United States)

    Jang, Kee-Taek; Ahn, Sangjeong


    -The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder. -To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder. -Review of relevant literatures indexed in PubMed. -Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ.

  18. Spontaneous cholecystocutaneous fistula as a primary manifestation of gallbladder adenocarcinoma associated with gallbladder lithiasis - case report. (United States)

    Micu, Bogdan Vasile; Andercou, Octavian Aurel; Micu, Carmen Maria; Militaru, Valentin; Jeican, IonuŢ Isaia; Bungărdean, Cătălina Ileana; Mogoantă, Stelian ŞtefăniŢă; Miclăuş, Dan Radu; Pop, Tudor Radu


    Spontaneous cholecystocutaneous fistula (SCF) is a rare complication of neglected calculous biliary disease and also an extremely rare complication of gallbladder neoplasm. This pathology has become even rarer because of prompt diagnosis and expedient surgical intervention for gallstones. So far, there is one published report of a SCF due to gallbladder adenocarcinoma. We present the case of a woman aged 87 years, admitted to the Vth Department of Surgery, Clinical Municipal Hospital of Cluj-Napoca (Romania) for a tumoral mass located in the epigastrium. In the epigastrium, the patient had three skin orifices of about 1-2 mm each, through which purulent secretion occurred. The abdominal ultrasound highlighted a cholecystocutaneous fistula with the presence of a subcutaneous gallstone. Intraoperatively, we found a cholecystocutaneous fistula, a 1 cm subcutaneous gallstone, gallbladder with thickened walls containing a cylinder-shaped gallstone of 5÷3 cm. Fistulectomy, gallstones extraction and cholecystectomy were performed. The histopathological examination highlighted gallbladder adenocarcinoma. In conclusion, SCF can be the first significant manifestation of gallbladder cancer associated with neglected calculous biliary disease.

  19. [The application of digestive endoscopic ultrasonography in the gallbladder pathology]. (United States)

    Roseau, Gilles


    A WELL DEFINED PATHOLOGY: Bilary lithiasis and vesicular parietal abnormalities constitute the totality of the gallbladder pathology. The surgical experience and widely current use of digestive imaging, notably ultrasonography, have contributed to enlightening our knowledge of this pathology. POTENTIAL DIAGNOSTIC PROBLEMS: There is no particular problem in the diagnosis of gallbladder lithiasis and its treatment is currently codified. However the discovery of thickened gallbladder wall or polyps increases the fear of gallbladder cancer. A FUNDAMENTAL ROLE FOR ENDOSCOPIC ULTRASONOGRAPHY: Within the framework of screening for cancer, endoscopic ultrasonography, the performance of which in gallbladder pathology has rarely been studied, appears promising. Other than its role in the control of the extension of gallbladder cancers, it provides reliable characterisation of most of the polyps. Hence its place today is unavoidable in the therapeutic decision trees of such affections.

  20. In vitro and in vivo accuracy of sonographic gallbladder volume determinations

    DEFF Research Database (Denmark)

    Andersen, I B; Monrad, H; Grønvall, S


    To assess gallbladder function, sonographic gallbladder volume determinations have been used with increasing frequency. This study presents a modified and automated procedure for gallbladder volume determinations using Simpson's rule of integration, Simpson's method. This method is a standard opt...

  1. Organotypic in vitro models of human cutaneous squamous cell carcinoma

    NARCIS (Netherlands)

    Commandeur, Suzan


    Skin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the high and rising prevalence of cutaneous SCC puts an increasingly high financial burden on society,

  2. Epac inhibits migration and proliferation of human prostate carcinoma cells

    NARCIS (Netherlands)

    Grandoch, M.; Rose, A.; ter Braak, M.; Jendrossek, V.; Ruebben, H.; Fischer, J. W.; Schmidt, M.; Weber, A. A.


    BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [(3)H

  3. Cancer of the gallbladder-Chilean statistics. (United States)

    Villanueva, Luis


    Chile has the world's highest rate of incidence as well as death from cancer of the gallbladder and biliary ducts. The problem is most acute in the southern provinces. These areas constitute the low average income associated with low educational attainment and a high rate of obesity compared with the rest of Chile. We could also include genetic factors related to processes of lithogenesis to these elements which are more common among the Mapuche. This population sub-group could benefit from special government programmes for early diagnosis and treatment of lithiasic disease and for the management of risk factors such as obesity. In this way, we could reduce the mortality rate of gallbladder cancer.

  4. Squamous Cell Carcinoma of the Distal Common Bile Duct


    Jain A; Juneja M; Naik S; Sharma S; Kapoor S; Sewkani A; Varshney S


    CONTEXT: Squamous cell carcinoma of the biliary tree is rare. Although few cases of squamous cell carcinoma of the intrahepatic bile-duct and gallbladder have been reported, until today, only four cases of squamous cell carcinoma of the extrahepatic bile duct have been reported in the literature. CASE REPORT: We present a case of squamous cell carcinoma of the distal common bile duct presenting with obstructive jaundice in a 60-year-old male which was successfully managed by a Whipple's pancr...

  5. Acalculous Diffuse Gallbladder Wall Thickening in Children


    Lee, Ji Haeng; No, Young Eun; Lee, Yeoun Joo; Hwang, Jae Yeon; Lee, Joon Woo; Park, Jae Hong


    Purpose Gallbladder (GB) wall thickening can be found in various conditions unrelated to intrinsic GB disease. We investigated the predisposing etiologies and the outcome of acalculous GB wall thickening in children. Methods We retrospectively analyzed 67 children with acalculous GB wall thickening who had visited our institute from June 2010 to June 2013. GB wall thickening was defined as a GB wall diameter >3.5 mm on abdominal ultrasound examination or computed tomography. Underlying diseas...

  6. Non-operative Management of Gallbladder Perforation After Blunt ...

    African Journals Online (AJOL)

    operative management of isolated traumatic gallbladder perforation. Key words: Cholecystectomy, cholecystorraphy, damage control surgery, endoscopic management. Department of General Surgery, East Kent University NHS. Foundation Trust ...

  7. Molecular typing for detection of high-risk human papillomavirus is a useful tool for distinguishing primary bladder carcinoma from secondary involvement of uterine cervical carcinoma in the urinary bladder. (United States)

    Kao, Hua-Lin; Lai, Chiung-Ru; Ho, Hsiang-Ling; Pan, Chin-Chen


    For patients with carcinoma of the urinary bladder and uterine cervix, distinguishing between metastasis and a second primary carcinoma has significant prognostic and therapeutic implications. The aim of this study was to investigate the prevalence of high-risk human papillomavirus (HR-HPV) in cervical carcinoma with secondary involvement of the bladder and primary bladder carcinoma, in order to explore whether the detection of HR-HPV could help to differentiate between the two. Paired bladder and cervix carcinoma specimens from 37 patients with cervical carcinoma with bladder involvement, four patients with bladder carcinoma with uterine cervical involvement and two patients with double primaries were studied with quantitative multiplex polymerase chain reaction and chromogenic in-situ hybridization. Three hundred and seventy-five bladder carcinomas and 220 cervical carcinomas were analysed as controls. All cases of cervical carcinoma with bladder involvement showed concordant HR-HPV-positive patterns. The four cases of bladder carcinoma with uterine involvement were negative for HR-HPV. HR-HPV was detected in the cervical carcinoma but not in the bladder carcinoma of the patients with double primaries. HR-HPV was detected in 91.9% of cervical carcinomas but in none of the bladder carcinomas in the control group. Molecular typing for HR-HPV detection is useful to distinguish bladder carcinoma from secondary involvement of cervical carcinoma. © 2015 John Wiley & Sons Ltd.

  8. Woodchuck hepatitis virus-induced carcinoma as a relevant natural model for therapy of human hepatoma. (United States)

    Gouillat, C; Manganas, D; Zoulim, F; Vitrey, D; Saguier, G; Guillaud, M; Ain, J F; Duque-Campos, R; Jamard, C; Praves, M; Trepo, C


    Eastern American woodchuck (Marmota monax), naturally infected with woodchuck hepatitis virus, a virus similar to human hepatitis B virus, develops liver cancer with a high prevalence. The aim of this work was to assess Marmota monax as a model of human hepatocellular carcinoma, especially to assess new potential adjuvant therapies after surgical resection. Forty-four woodchuck hepatitis virus-infected animals were regularly screened by ultrasound examination from the age of 18 months and for a 30-month period. One or more liver tumors were diagnosed in 31 animals (70%). Five of them with multifocal tumor or poor general status were considered unsuitable for surgery. The other 26 were operated on. At laparotomy no tumor was found in three. The 18 liver tumors studied were hepatocellular carcinomas, grossly and microscopically similar to human hepatocellular carcinoma. Peritumoral parenchyma studied in 13 specimens was always non-cirrhotic but adequate staining demonstrated patterns of fibrosis in four cases. Clear evidence of chronic active hepatitis, periportal hepatitis and steatosis were demonstrated in five, seven and one of the 13 specimens, respectively. Tumors were treated by tumorectomy in eight animals, by alcoholization in seven and by laser photocoagulation in one. A simple tumor biopsy was performed in the other seven. Ten animals died postoperatively. All the survivors in the tumorectomy group died from tumor recurrence within 10-18 months after surgery. It is concluded that woodchuck hepatitis virus-induced liver carcinoma is a natural model of human hepatocellular carcinoma with similar pathology and natural history, including early ultrasonic detection and tumor recurrence after resection. Tumor excision is feasible in this animal model, which now provides the basis for assessment of new potential adjuvant therapies for human hepatocellular carcinoma in an attempt to reduce the high recurrence rate after surgical resection in humans.

  9. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.

    Directory of Open Access Journals (Sweden)

    Fang Peng

    Full Text Available BACKGROUND: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC in mice. METHODOLOGY/PRINCIPAL FINDINGS: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF, matrix metalloproteinase-2 (MMP-2, MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF increased. CONCLUSIONS: Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.

  10. Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells. (United States)

    Lee, Jong Seok; Hong, Eock Kee


    It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that HE acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma. (United States)

    Maddalena, Francesca; Simeon, Vittorio; Vita, Giulia; Bochicchio, Annamaria; Possidente, Luciana; Sisinni, Lorenza; Lettini, Giacomo; Condelli, Valentina; Matassa, Danilo Swann; Li Bergolis, Valeria; Fersini, Alberto; Romito, Sante; Aieta, Michele; Ambrosi, Antonio; Esposito, Franca; Landriscina, Matteo


    TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors. TRAP1 is upregulated at the transition between low- and high-grade adenomas, in in situ carcinomas and in about 60% of human colorectal carcinomas, being downregulated only in a small cohort of tumors. The analysis of TCGA database showed that a subgroup of colorectal tumors is characterized by gain/loss of TRAP1 copy number, this correlating with its mRNA and protein expression. Interestingly, TRAP1 is co-expressed with the majority of its client proteins and hierarchical cluster analysis showed that the upregulation of TRAP1 and associated 6-protein signature (i.e., IF2α, eF1A, TBP7, MAD2, CDK1 and βCatenin) identifies a cohort of metastatic colorectal carcinomas with a significantly shorter overall survival (HR 5.4; 95% C.I. 1.1-26.6; p=0.037). Consistently, the prognostic relevance of TRAP1 was confirmed in a cohort of 55 metastatic colorectal tumors. Finally, TRAP1 positive expression and its prognostic value are more evident in left colon cancers. These data suggest that TRAP1 protein network may provide a prognostic signature in human metastatic colorectal carcinomas.

  12. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.


    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  13. Usefulness of lavage cytology during endoscopic transpapillary catheterization into the gallbladder in the cytological diagnosis of gallbladder disease. (United States)

    Naito, Yoshiki; Okabe, Yoshinobu; Kawahara, Akihiko; Taira, Tomoki; Isida, Yusuke; Kaji, Ryouhei; Sata, Michio; Ureshino, Hiroki; Mikagi, Kazuhiro; Kinoshita, Hisafumi; Yasumoto, Makiko; Kusano, Hironori; Kage, Masayoshi; Yano, Hirohisa


    Many studies have reported methods of cell collection involving percutaneous transhepatic cholangiodrainage (PTCD) and fine-needle aspiration cytology for the diagnosis of gallbladder disease. However, few studies have described the use of a transpapillary approach, i.e., endoscopic transpapillary catheterization into the gallbladder (ETCG). In this study, we analyzed cells collected by ETCG to evaluate its usefulness in the cytological diagnosis of gallbladder disease. The subjects were 19 patients who had undergone ETCG for the diagnosis of gallbladder disease. Of these patients, 11 and 8 had gallbladder cancer and benign gallbladder disease, respectively. We also evaluated the diagnostic accuracy of PTCD cytology performed in 15 patients with gallbladder cancer.Specimens were cytologically diagnosed as normal or benign, indeterminate, suspected malignancy, malignant, and inadequate in 47% (9/19), 11% (2/19), 0% (0/19), 37% (7/19), and 5% (1/19) of patients, respectively. Specimens were diagnosed as malignant, indeterminate, normal or benign, and inadequate in 7, 2, 1, and 1, respectively, of the 11 patients diagnosed with gallbladder cancer. The sensitivity and specificity of ETCG cytology were 78 and 100%, respectively, whereas the diagnostic accuracy of PTCD cytology was 20% (3/15). None of the patients developed complications of ETCG. Despite its technical difficulty, ETCG for bile cytology allows the collection of adequate cell numbers from patients with benign disease or gallbladder cancer and facilitates a cytological diagnosis, making it a useful method for collecting cells. (c) 2009 Wiley-Liss, Inc.

  14. [Human papilloma viruses: other risk factor of head and neck carcinoma]. (United States)

    Woto-Gaye, G; M'Farrej, M K; Doh, K; Thiam, I; Touré, S; Diop, R; Dial, C


    Head and neck carcinoma (HNC) occupy the sixth place as the most frequent type of cancer worldwide. Next to alcohol and tobacco intoxication, other risk factors (RF) are suspected, including the human papilloma viruses (HPVs). The aim of this study was to highlight the prevalence of HPVs and histo-epidemiological characteristics of HNC HPV+ in Senegal. This is a prospective, multicenter preliminary study of 18 months (January 1, 2012-June 30, 2014). The cases of HNC histologically confirmed in Senegal were then sent to the bio-pathology department of the Curie Institute in Paris to search HPVs. In the 90 included cases, the PCR technique was successful in 54 cases (60%). HPVs were found in seven cases, that is, a prevalence of 13%. HPVs were associated with 5 cases of hypopharyngeal carcinoma and 2 cases of carcinoma of the oral cavity. Patients with HNC HPV+ had a median age of 42 years against 49 years for HPV-patients. Three patients (42.8%) with HPV+ carcinomas were smokers. Of the 47 HPV-patients, 40 patients (87.1%) had alcohol intoxication and/or smoking. The concept of oral sex was refuted by all our patients. Squamous cell carcinoma was the only histological type found. HPV+ cell carcinoma showed no specific histological appearance. HPVs are another certain RF of HNC in Senegal. The major therapeutic and prognostic impact of HPVinduced cancers requires the systematic search of the viruses by the PCR technique.

  15. Cellular binding proteins for vitamin A in human carcinomas and in normal tissues. (United States)

    Palan, P R; Romney, S L


    Blinded analyses of the concentrations of binding proteins for retinol and retinoic acid (CRABP) in homogenates of cancer and normal tissue aliquots obtained from human cervix, endometrium, ovary, breast, and lung were carried out by the sucrose gradient ultracentrifugation technique. In carcinomas of the cervix and endometrium, CRABP mean values of 50.4 and 123.2 pmol/g tissue, respectively were detected. Such concentrations represent a 3- and 4-fold increase over the mean values of CRABP in the normal cervix (16.9 pmol/g) and normal endometrium (30.8 pmol/g), respectively. In carcinomas of the ovary, the mean CRABP level was 128.6 pmol/g compared to the maximal mean value of less than or equal to 0.46 pmol/g in the normal ovary. Elevated levels of CRABP were also found in breast and lung carcinomas compared to the amounts detected in the same patient in normal tissue aliquots of the same organ. The differences between CRABP concentrations in cervical, endometrial, ovarian, and breast carcinomas and those in normal tissue are statistically significant. In contrast, cellular retinol-binding protein concentrations were reduced in the endometrial, ovarian, breast, and lung carcinomas compared to normal tissues. There were no significant differences between the log-mean concentrations of cellular retinol-binding proteins in the cytosols from tissue aliquots of carcinoma of the cervix and those in the cytosols from tissue aliquots of normal cervix.

  16. 4-Methoxycinnamaldehyde inhibited human respiratory syncytial virus in a human larynx carcinoma cell line. (United States)

    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching


    4-Methoxycinnamaldehyde, an active constituent of Agastache rugosa, was examined for its cytoprotective activity against RSV by XTT method in human larynx carcinoma cell line. 4-Methoxycinnamaldehyde could effectively inhibit cytopathic effect of RSV (p<0.0001) with an estimated IC(50) of 0.055microg/ml and a selectivity index (SI) of 898.2. 4-Methoxycinnamaldehyde (0.03microg/ml) could inhibit viral entrance by interfering viral attachment (IC(50) of 0.06microg/ml; p<0.0001) and internalization (IC(50) of 0.01microg/ml; p<0.0001). 4-Methoxycinnamaldehyde significantly increased the basal production of IFN (p=0.0015), but not the virus-induced IFN production. Therefore, its cytoprotective activity against RSV was not mediated by interferon. In conclusion, 4-methoxycinnamaldehyde might be helpful to manage the disease induced by RSV infection.

  17. Effect of ultrasound combined with determination of CA19-9 and hs-CRP on the accuracy of early diagnosis of gallbladder cancer

    Directory of Open Access Journals (Sweden)

    Hang-yu ZHANG


    Full Text Available Objective  To investigate the value of ultrasound combined with tumor marker CA19-9 and high sensitivity C reactive protein (hs-CRP on the accuracy of early diagnosis of gallbladder cancer. Methods  Ninety-five patients with pathologically confirmed primary gallbladder cancer who received cholecystectomy from Jan. 2008 to Jan. 2013 in our hospital were included in the study. The study also included 51 patients with benign cystic lesions and 51 healthy adults. In all patients, results of pathological examination, B-ultrasound, serum CA19-9 and hs-CRP detection were obtained. In all the healthy adults gallbladder diseases were ruled out, but all of them received serum CA19-9 and hs-CRP determination. Results  Of 95 patients with primary gallbladder cancer, B-ultrasound showed nodules in the gallbladder lumen in 31, tumor mass in 40, and thickened wall in 24. Histological examination showed adenocarcinoma in 87 cases, adenosquamous carcinoma in 6, and squamous carcinoma in 2. There was a statistical difference in hs-CRP and CA19-9 levels between the groups (P<0.05, and the highest level appeared in gallbladder cancer group. There was a high sensitivity but low specificity of CA19-9 or hs-CRP in the diagnosis of primary gallbladder cancer. The sensitivity and specificity were 74.7% and 75.0% when primary gallbladder cancer was diagnosed with B-ultrasound. The positive values of CA19-9 and hs-CRP were ≥100U/ml and ≥6mg/L respectively, when they were combined with B-ultrasound as a single serology factor. When both B-ultrasound and serum levels of CA19-9 and hs-CRP were positive, the diagnostic sensitivity and specificity were 71.6% and 84.4% respectively. When B-ultrasound or serum CA19-9 and hs-CRP were positive, the diagnostic sensitivity and specificity were 98.9% and 66.7% respectively. Conclusions  Combination of B-ultrasound and determination of serum of CA19-9 and hs-CRP can improve the accuracy of the diagnosis of gallbladder

  18. Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and lung carcinoma cells. (United States)

    Sadava, David; Coleman, Aaron; Kane, Susan E


    Multi-drug resistance due in part to membrane pumps such as P-glycoprotein (Pgp) is a major clinical problem in human cancers. We tested the ability of liposomally-encapsulated daunorubicin (DR) to overcome resistance to this drug. A widely used breast carcinoma cell line originally selected for resistance in doxorubicin (MCF7ADR) was 4-fold resistant to DR compared to the parent MCF7 cells (IC50 79 nM vs. 20 nM). Ovarian carcinoma cells (SKOV3) were made resistant by retroviral transduction of MDR1 cDNA and selection in vinblastine. The resulting SKOV3MGP1 cells were 130-fold resistant to DR compared to parent cells (IC50 5700 nM vs. 44 nM). Small-cell lung carcinoma cells (H69VP) originally selected for resistance to etoposide were 6-fold resistant to DR compared to H69 parent cells (IC50 180 nM vs. 30 nM). In all three cases, encapsulation of DR in liposomes as Daunoxome (Gilead) did not change the IC50 of parent cells relative to free DR. However, liposomal DR overcame resistance in MCF7ADR breast carcinoma cells (IC50 20 nM), SKOV3MGP1 ovarian carcinoma cells (IC50 237 nM) and H69VP small-cell lung carcinoma cells (IC50 27 nM). Empty liposomes did not affect the IC50 for free DR in the three resistant cell lines, nor did empty liposomes affect the IC50 for other drugs that are part of the multi-drug resistance phenotype (etoposide, vincristine) in lung carcinoma cells. These data indicate the possible value of liposomal DR in overcoming Pgp-mediated drug resistance in human cancer.

  19. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans (United States)

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J


    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  20. Amplification and over-expression of the neu oncogene in human breast carcinomas

    NARCIS (Netherlands)

    van de Vijver, M. J.; Mooi, W. J.; Peterse, J. L.; Nusse, R.


    Amplification of the neu (or c-erbB-2 or HER) oncogene is found to be present in 15-30% of human breast carcinomas and has been reported to correlate with poor prognosis. We briefly review the literature on this subject with emphasis on our own results on immunohistochemical detection of neu

  1. The sinonasal tract: another potential "hot spot" for carcinomas with transcriptionally-active human papillomavirus

    NARCIS (Netherlands)

    Lewis, J.S., Jr.; Westra, W.H.; Thompson, L.D.; Barnes, L.; Cardesa, A.; Hunt, J.L.; Williams, M.D.; Slootweg, P.J.; Triantafyllou, A.; Woolgar, J.A.; Devaney, K.O.; Rinaldo, A.; Ferlito, A.


    While high risk human papillomavirus (HPV) is well established as causative and clinically important for squamous cell carcinoma (SCC) of the oropharynx, its role in non-oropharyngeal head and neck SCC is much less clearly elucidated. In the sinonasal region, in particular, although it is a

  2. Gallbladder cancer and nutritional risk factors in Chile (United States)

    Navarro Rosenblatt, Deborah; Durán Agüero, Samuel


    Gallbladder cancer is the most malign neoplasm of the biliary tract. Chile presents the third highest prevalence of gallbladder cancer in the Americas, being Chilean women from the city of Valdivia the ones with the highest prevalence. The main risk factors associated with gallbladder cancer are: sex, cholelithiasis, obesity, ethnicity, chronic inflammation, history of infection diseases such as Helicobacter pyloriand Salmonellaand family history of gallbladder cancer. In Chile gallbladder cancer mortality is close to prevalence level. This is related to the silent symptomatology of this cancer, as well as the lack of specific symptoms. The high prevalence of obesity and infectious diseases present in Chile are two of the main risk factors of gallbladder cancer and Chile has prevalence of obesity close to 30%. The aim of this literary review is to inform and summarize the main risk factors of gallbladder cancer that are prevalent in Chile, in order to be able to focus preventive and management interventions of this risk factor for the reduction in prevalence and mortality of gallbladder cancer in Chile.

  3. Dynamic cholescintigraphy: induction and description of gallbladder emptying

    DEFF Research Database (Denmark)

    Toftdahl, D B; Højgaard, L; Winkler, K


    seen in the six patients. The measurements of EF30 in healthy subjects scattered more widely around the mean compared to the mean EF and EFmax, which indicates poorer ability to separate normal from abnormal gallbladder emptying. Intravenous bolus injection of CCK-8 resulted in incomplete gallbladder...

  4. Isolated gallbladder perforation following blunt abdominal trauma: A ...

    African Journals Online (AJOL)

    ... to peptic ulcer perforation. Intraoperatively, he was then discovered to have an isolated gallbladder perforation. This is a rare condition in which the diagnosis is often delayed or missed as was the case in our patient. To the best of our knowledge, this is the first reported case of isolated gallbladder perforation in Nigeria, ...

  5. Double gallbladder with different disease entities: A case report

    Directory of Open Access Journals (Sweden)

    Vijayaraghavan R


    Full Text Available We report a rare case of gallbladder duplication in a young male patient with acute pyocoele in one vesicle and acute cholecystitis with cystadenoma in the other; another unusual feature was the absent or obliterated cystic duct in the proximal vesicle and non-communication with the second vesicle or the biliary system. Ultrasound examination had suggested a septate gallbladder; the diagnosis of dual gallbladder was made per-operatively during separation of the distal moiety which was presumed to be an adherent duodenum initially. Intraoperative cholecystogram confirmed the diagnosis and both gallbladders were removed successfully laparoscopically. A high degree of awareness, detailed preoperative investigations when anomalies are suspected and intraoperative cholangiography are necessary for accurate detailing of the biliary tree to avoid inadvertent damage to the biliary ductal system and overlooking of second or third gallbladder during surgery.

  6. Cryopreservation of human colorectal carcinomas prior to xenografting

    Directory of Open Access Journals (Sweden)

    Krohn Mathias


    Full Text Available Abstract Background Molecular heterogeneity of colorectal carcinoma (CRC is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Methods Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23 or after cryopreservation (N = 31; up to 643 days. Results Take rates after cryopreservation were satisfactory (71% though somewhat lower than with tumor tissues fresh from surgery (74%, but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11 was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Conclusions Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres for (preclinical studies of novel therapies or for basic research.

  7. Galectin-3 expression in human papillary thyroid carcinoma. (United States)

    Sawangareetrakul, Phannee; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Svasti, Jisnuson


    Previous studies have suggested that galectin-3 expression was markedly elevated in papillary thyroid carcinoma compared to other thyroid diseases. In order to better understand this protein, galectin-3 from papillary thyroid carcinoma was partially purified by affinity chromatography on lactose-agarose. Proteins eluted from the column were separated by SDS-PAGE, and galectin-3 was detected with antibodies against the N-terminus and C-terminus of galectin-3. Some protein bands from the lactose binding fraction were also selected for identification by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Seven protein bands, with molecular weights ranging from 16 kDa to 31 kDa, were identified as galectin-3. The antibody raised against the C-terminus of galectin-3 gave a strong band for one of the bands detected by the N-terminal antibody and weak bands for the other three. One additional dark immunoreactive band with an approximate molecular weight of 20 kDa, was also detected by the C-terminal galectin-3 antibody. To determine the structural differences of each protein band, N-terminal amino acid sequencing of the seven protein bands was conducted. The three upper bands were N-terminally blocked, while the other bands had N-terminal amino acid sequences starting at positions Gly35, Gly65 (2 bands) and Ala100, respectively. Further studies are necessary to determine whether these are due to nonspecific proteolysis or post-translation modification.

  8. Squamous cell carcinoma antigen in human liver carcinogenesis. (United States)

    Guido, M; Roskams, T; Pontisso, P; Fassan, M; Thung, S N; Giacomelli, L; Sergio, A; Farinati, F; Cillo, U; Rugge, M


    Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages. To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers. 55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale. SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (pHCC (p = 0.000). A barely significant difference (p = 0.49) was observed between LG-DNs and HG-DNs, while no difference in SCCA expression was detected between HG-DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p = 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs. This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.

  9. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yingjian Liang

    Full Text Available Diphenyl difluoroketone (EF24, a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

  10. Cancer of the gallbladder?Chilean statistics




    Chile has the world?s highest rate of incidence as well as death from cancer of the gallbladder and biliary ducts. The problem is most acute in the southern provinces. These areas constitute the low average income associated with low educational attainment and a high rate of obesity compared with the rest of Chile. We could also include genetic factors related to processes of lithogenesis to these elements which are more common among the Mapuche. This population sub-group could benefit from s...

  11. Incarcerated umbilical cord hernia containing the gallbladder

    Directory of Open Access Journals (Sweden)

    Ann M. Kulungowski


    Full Text Available A 16 day-old boy infant with an umbilical mass underwent operative exploration of the umbilicus. The mass proved to be a gallbladder incarcerated in a hernia of the umbilical cord. Distinguishing an omphalocele from an umbilical cord hernia is not obvious and can be arbitrary. Morphologically, the two terms both describe congenital abdominal wall defects covered by a membrane, typically containing abdominal organs. Subtle differences and clinical features between omphalocele and umbilical cord hernia are highlighted in this report.

  12. Leptin regulates gallbladder genes related to absorption and secretion. (United States)

    Swartz-Basile, Deborah A; Lu, Debao; Basile, David P; Graewin, Shannon J; Al-Azzawi, Hayder; Kiely, James M; Mathur, Abhishek; Yancey, Kyle; Pitt, Henry A


    Dysregulation of gallbladder ion and water absorption and/or secretion has been linked to cholesterol crystal and gallstone formation. We have recently demonstrated that obese, leptin-deficient (Lep(ob)) mice have enlarged gallbladder volumes and decreased gallbladder contractility and that leptin administration to these mice normalizes gallbladder function. However, the effect of leptin on gallbladder absorption/secretion is not known. Therefore, we sought to determine whether leptin would alter the expression of genes involved in water and ion transport across the gallbladder epithelium. Affymetrix oligonucleotide microarrays representing 39,000 transcripts were used to compare gallbladder gene-expression profiles from 12-wk-old control saline-treated Lep(ob) and from leptin-treated Lep(ob) female mice. Leptin administration to Lep(ob) mice decreased gallbladder volume, bile sodium concentration, and pH. Leptin repletion upregulated the expression of aquaporin 1 water channel by 1.3-fold and downregulated aquaporin 4 by 2.3-fold. A number of genes involved in sodium transport were also influenced by leptin replacement. Epithelial sodium channel-alpha and sodium hydrogen exchangers 1 and 3 were moderately downregulated by 2.0-, 1.6-, and 1.3-fold, respectively. Carbonic anhydrase-IV, which plays a role in the acidification of bile, was upregulated 3.7-fold. In addition, a number of inflammatory cytokines that are known to influence gallbladder epithelial cell absorption and secretion were upregulated. Thus leptin, an adipocyte-derived cytokine involved with satiety and energy balance, influences gallbladder bile volume, sodium, and pH as well as multiple inflammatory cytokine genes and genes related to water, sodium, chloride, and bicarbonate transport.

  13. [Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx]. (United States)

    Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso


    Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. (United States)

    Zhang, Xin-Yu; Yang, Shu-Meng; Zhang, Hao-Peng; Yang, Yue; Sun, Shi-Bo; Chang, Jian-Ping; Tao, Xuan-Chen; Yang, Tuo-Yun; Liu, Chun; Yang, Yan-Mei


    Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Synergistic anti-tumor effect of KLF4 and curcumin in human gastric carcinoma cell line. (United States)

    Ji, Jun; Wang, He-Shuang; Gao, Yan-Yan; Sang, Li-Min; Zhang, Li


    Kruppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC- 823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

  16. The value of sonographic gallbladder wall patterns in differentiating malignant from benign ascites

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    Lee, Young Rae; Park, Hae Won; Lee, Young Uk; Oh, Won Ja [Koryo General Hospital, Seoul (Korea, Republic of)


    This investigation evaluates whether the appearance and thickness of the gallbladder (GB) wall can be clinically useful to determine the etiology of ascites by ultrasonography. Another purpose of this study is to verify the existence of statistically significant relationship between GB wall patterns and serum albumin level. Findings on ultrasonogram were reviewed retrospectively in 90 patients with ascites. The statistical analysis of the results reveals no correlation between hypoalbuminemia and GB wall patterns (P>0.05). There was a significant difference in GB wall patterns between benign (group 1 and 2) and malignant (group 3 and 4) conditions (P>0.05). The carcinoma, with the exception of hepatocellular the gallbladder wall was significantly thicker in the cirrhosis brougs than in the malignant group. Twenty-seven patients (87%) in group 1 had thickened GB walls, whereas 16 patients (76%) in group 3 showed normal single layered GB walls. This difference was statistically significant (P>0.05). However no statistically significant difference was found between liver cirrhosis (group 1) and liver cirrhosis associated with hepatocellular carcinoma (group 4) (P>0.05). Also, with the except of hepatocellular carcinoma (group 3) there also was no significant difference found between benign noncirrhotic pathology (group 2) and malignancy. These results suggests that there is a distant sonographic appearance of the GB wall according to different ascitis etiologies. This can pathology be seen when comparing patients with liver carrhosis and malignancy other than hepatocellular carcinoma. However sonographic findings of the GB wall patterns in ascites lacks diagnostic value in differentiating benign from malignant disease causing ascites.

  17. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

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    Sadat Noori


    Full Text Available Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences.Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4.Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed.Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated.

  18. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

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    Drosten Christian


    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  19. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

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    Cheng-Yuan Wang


    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  20. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells

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    Alarifi S


    Full Text Available Saud Alarifi,1 Daoud Ali,1 Saad Alkahtani,1 Maqsood A Siddiqui,2 Bahy A Ali2,31Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 2DNA Research Chair, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 3Genetic Engineering & Biotechnology Research Institute City for Scientific Research and Technology Applications, Alexandria, EgyptBackground: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl-2, 5-diphenyl tetrazolium bromide and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01 reduction in glutathione (15.67% and 26.52%, with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01, superoxide dismutase (76.42% and 81.09%; P < 0.01, catalase (73.33% and 76.47%; P < 0.01, and reactive oxygen species generation (44.04% and 56.14%; P < 0.01 after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01 induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.Keywords: arsenic trioxide, DNA damage, hepatocellular carcinoma

  1. Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil. (United States)

    Petito, Guilherme; Carneiro, Megmar Aparecida Dos Santos; Santos, Sílvia Helena de Rabello; Silva, Antonio Marcio Teodoro Cordeiro; Alencar, Rita de Cassia; Gontijo, Antonio Paulo; Saddi, Vera Aparecida

    Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and alcohol consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9-36.6) of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil

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    Guilherme Petito

    Full Text Available Abstract Introduction Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. Objectives This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. Methods This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Results Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78% and alcohol consumption (70.8% were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9–36.6 of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. Conclusion The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas.

  3. Routine extra-hepatic bile duct resection in gallbladder cancer patients without bile duct infiltration: A systematic review. (United States)

    Nigri, Giuseppe; Berardi, Giammauro; Mattana, Chiara; Mangogna, Livia; Petrucciani, Niccolò; Sagnotta, Andrea; Aurello, Paolo; D'Angelo, Francesco; Ramacciato, Giovanni


    The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra-hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph-node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  4. Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery (United States)


    Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Malignant Neoplasm; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  5. [Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver]. (United States)

    Horváth, Evelin; Balla, Bernadett; Kósa, János; Lakatos, Péter András; Lazáry, Áron; Németh, Dániel; Jozilan, Hasan; Somorácz, Áron; Korompay, Anna; Gyöngyösi, Benedek; Borka, Katalin; Kiss, András; Kupcsulik, Péter; Schaff, Zsuzsa; Szalay, Ferenc


    1,25-Dihydroxy vitamin D 3 mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D 3 -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (pexpressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D 3 , providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

  6. Periodic contractions of the canine gallbladder during the interdigestive state. (United States)

    Itoh, Z; Takahashi, I


    Interdigestive contractile activity of the gallbladder, the stomach, and the duodenum was measured by means of chronically implanted force transducers in five conscious dogs. During the interdigestive state, contractions of the gallbladder were identified to be closely associated with the initial period of phase II of the interdigestive migrating contractions (IMC) in the duodenum. The mean contractile force of the gallbladder during this phase was 6.5 +/- 0.77 g, which corresponded to approximately 80% of the force of the postprandial contractions. When the duodenum exhibited phase II contractions, the gallbladder had already returned to the resting level. Intravenous infusion of synthetic motilin induced IMC in the stomach and duodenum and during the initial period of motor response of the duodenum reproduced contractions in the gallbladder that were identical to the natural contractions as to their period and pattern. We cannot yet ascribe the interdigestive contractions observed in the gallbladder to the direct action of motilin, but the present study clearly indicates that the gallbladder contracts even in the interdigestive state, and the contractions are associated with the phase II contractions in the duodenum.

  7. Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy

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    Chang Seok Bang


    Full Text Available Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116. In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P=0.01 and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P=0.04 were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P=0.004 was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.

  8. Prenatal Nonvisualization of the Gallbladder: A Diagnostic and Prognostic Dilemma. (United States)

    Ruiz, Aina; Robles, Ana; Salva, Francisca; Filgueira, Ana; Díaz, Cristina; Juan, Miquel; Tubau, Albert


    Nonvisualization of the fetal gallbladder has been associated with benign conditions such as isolated gallbladder agenesis or severe diseases such as biliary atresia (BA). Recently, gamma-glutamyl transpeptidase (GGTP) fetal blood levels were reported as useful after 22 weeks. To determine the contribution of fetal blood GGTP levels after 22 weeks, based on 2 cases. Case 1: 20+4-week secundipara, with subcutaneous edema and pleural effusion. At 24+4 weeks, the gallbladder could not be visualized. Progressive hydrops deterioration was observed. 32+2-week magnetic resonance imaging (MRI) confirmed nonvisualization of the gallbladder. BA was suspected. The patient decided to terminate the pregnancy and fetal blood sample was obtained at feticide. GGTP was 573 IU/L. Fetal necropsy confirmed BA. Case 2: At the 22+6- and 24+0-week ultrasound scan, the gallbladder could not be visualized. Amniocentesis was offered, but declined by the patient. MRI at 35+0 weeks failed also to visualize it. Fetal cord blood sample at delivery was obtained, and GGTP was 129 IU/L. Ultrasound confirmed gallbladder agenesis with normal extra- and intrahepatic bile ducts. Cases of nonvisualized gallbladder after 22 weeks have rarely been reported in the literature. Until now, no standard management has been proposed. Our cases support the potential usefulness of fetal blood digestive enzymes. © 2017 S. Karger AG, Basel.

  9. An alien in the gallbladder. A rare case of biliary ascariasis in an Italian emergency department

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    Enrico Ferri


    Full Text Available Ascariasis is a common infection in many developing countries. The prevalence of ascariasis is related to poverty, poor hygienic and sanitary conditions. The adult form of Ascaris lumbricoides usually resides in the human intestinal lumen (more frequently in the jejunum and middle ileum and does not cause symptoms. However, it can occasionally cause severe complications such as intestinal obstruction or perforation peritonitis. Its migration into the biliary tract is not uncommon but gallbladder involvement is very rare. Abdominal ultrasonography is essential to detect the presence of this parasite. In this article, we describe the radiologic findings, clinical manifestations and successful medical treatment of a patient with gallbladder ascariasis diagnosed in an emergency setting.

  10. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

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    Qin X


    Full Text Available Xian Qin,1 Yajun Wan,1 Saiying Wang,2 Min Xue1 1Department of Obstetrics and Gynecology, 2Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China Background: In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p in human cervical carcinoma.Methods: The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2, in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration.Results: miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration

  11. Expression Patterns of Glucose Transporter-1 Gene and Thyroid Specific Genes in Human Papillary Thyroid Carcinoma

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    Kim, Sungeun; Chung, Junekey; Min Haesook and others


    The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades. Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n=13) and relatively less differentiated group (n=11). Glut-1 gene expression was significantly higher in the less differentiated group (0.66±0.04) than in the well-differentiated group (0.59±0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67±0.20, PD: 0.65±0.21, TG: 0.74±0.16) than in the less differentiated group (NIS: 0.36±0.05, PD: 0.49±0.08, TG: 0.60±0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD. The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.

  12. Cyclic AMP phosphodiesterase activity in human gingival carcinoma. (United States)

    Spoto, Giuseppe; Fioroni, Massimiliano; Rubini, Corrado; Di Nicola, Maurizio; Di Pietrantonio, Francesco; Di Matteo, Elisabetta; Piattelli, Adriano


    The phosphodiesterases (PDEs) are responsible for the hydrolysis of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), to their corresponding monophosphates with a fundamental role in the transduction of the intracellular signals. At least 11 different enzymatic isoforms have been identified, which are listed according to their specificity or affinity for the substratum, identity of the amino acid sequence, cofactor, and inhibitor sensitivity. Variations in PDE activity have been found in different pathologies, and they have also been correlated to different pathological e/o physiological mechanisms, such as cellular differentiation, apoptosis, and tumor invasivity. In this study, we have evaluated cAMP PDE activity in patients with carcinoma of the gingiva, with the purpose of correlating differences in its development and progression. The same enzymatic activity has been used to evaluate differences between patients with lymph node involvement (group N(+)), and patients without lymph node involvement (N(-)). The analysis of PDE activity and the cAMP assay was performed by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cAMP was confirmed with the enzyme-linked immunoabsorption assay (EIA). The differences between control and N(-) groups (P = 0.0433), and between control and N(+) groups (P = 0.0156) were statistically significant. PDE3A was also evaluated immunohistochemically in lymph-node negative and lymph-node positive cases. The differences between the two groups were statistically significant (P = 0.0397).

  13. Characterization of a human ovarian carcinoma cell line: UCI 101. (United States)

    Fuchtner, C; Emma, D A; Manetta, A; Gamboa, G; Bernstein, R; Liao, S Y


    A new epithelial ovarian carcinoma cell line (UCI 101) has been established from the ascitic fluids and solid tumor of a patient with progressive papillary adenocarcinoma of the ovary shown previously to be refractory to combination chemotherapy consisting of cyclophosphamide, Adriamycin, and cisplatin as well as single-agent chemotherapy of taxol and high-dose cisplatin. The UCI 101 cell line grows well with an in vitro doubling time of 24 hr. The cell line expresses the B 72.3 (Tag 72), CA125, MH99 (ESA), and E29 (EMA) cell surface antigens and AE1/AE3 cytokeratins. This cell line overexpresses (as determined by immunocytochemistry) both p-glycoprotein and the epidermal growth factor receptor. The in vitro drug response to single agents including Adriamycin, cisplatin, dequalinium chloride, etoposide, 5-fluorouracil, taxol, and tumor necrosis factor was examined. Intraperitoneal transplantation of the cells into athymic mice resulted in foci of tumor on all peritoneal surfaces including the viscera and diaphragm ultimately leading to solid bulky disease with massive production of ascites. High levels of CA125 (> 500 units/ml) were detected in the serum of tumor-bearing mice. Cytogenetic analysis of cultured cells shows several marker chromosomes containing deletions, duplications, and translocations. Cytologic and histologic evaluation of the xenograft revealed morphological characteristics identical to those of the original tumor.

  14. Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ

    DEFF Research Database (Denmark)

    Junge, Jette; Poulsen, H; Horn, T


    whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16...... and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR....... No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva....

  15. Antiproliferative and apoptotic effect of Pleurotus ostreatus on human mammary carcinoma cell line (michigan cancer foundation-7

    Directory of Open Access Journals (Sweden)

    Krishnamoorthy Deepalakshmi


    Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.


    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc


    Full Text Available Cervical carcinoma with squamous cells has many of the characteristics of avenereal disease: high incidence (over 500.000 cases every year, an increased frequency for the women with multiple sex partners and the presence of one of the papillomavirus genotypes with a high carcinogenic risk (HPV 16, 18, 31 and 45 in 100% of the cases. Material and methods.In the period of time 2001-2012, in the Department of Obstetrics and Gynecology belonging to “Sf. Apostol Andrei” Emergency Hospital in Galaţi, 5047 women were hospitalized under the suspicion of having cervical neoplasia.As part of the screening programme, the women belonging to the high risk group are tested for HPV by using Hybrid Capture 2 (HC2.Results and discussions.The seropositive women’s risk of having a persistent HPV infection is 7 times higher than in the case of the seronegative ones, with the same age. This risk is double for the women with CD4 lymphocytes below 200/mmc.Infection with cancer-causing HPV types is limited to the epithelium of the uterine exocervix and it does not spread to other parts of the body. Conclusions. Cervical cancer is caused by the oncogenic types of HPV, types 16 and 18 being responsible for over 70% of the cases. It represents the second cause of mortality by cancer for the women between 15 and 44 years old. Anti-HPV vaccination comes as a partner of the screening programmes aiming to reduce the incidence and mortality by cervical cancer.

  17. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.


    Bang, Y J; Pirnia, F; Fang, W G; Kang, W K; Sartor, O; Whitesell, L; Ha, M J; Tsokos, M.; Sheahan, M D; Nguyen, P.


    Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analog...

  18. Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line. (United States)

    Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L


    Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

  19. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide (United States)

    Ouyang, Gao-Liang; Cai, Qiu-Feng; Liu, Min; Chen, Rui-Chuan; Huang, Zhi; Jiang, Rui-Sheng; Chen, Fu; Hong, Shui-Gen; Bao, Shi-Deng


    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer. METHODS: Effects of HMBA on the growth of human hepatocellular carcinoma SMMC-7721 cells were assayed by MTT chronometry. Apoptosis induced by HMBA was detected by phase-contrast microscopy, flow cytometry, propidium iodide staining and immunocytochemical analysis. RESULTS: The growth of SMMC-7721 cells was significantly inhibited by HMBA, and the growth inhibitory rate was 51.1%, 62.6%, 68.7% and 73.9% respectively after treatment with 5.0, 7.5, 10.0 and 12.5 mmol/L of HMBA. In the cells treated with 10 mmol/L of HMBA for 72 h, the population of cells at sub-G1 phase significantly increased, and the apoptotic bodies and condensed nuclei were detected. Moreover, treatment of SMMC-7721 cells with 10 mmol/L of HMBA down-regulated the expression of Bcl-2 anti-apoptotic protein, while slightly up-regulated the level of pro-apoptotic protein Bax. CONCLUSION: Treatment with 10.0 mmol/L of HMBA can significantly inhibit the growth and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells by decreasing the ratio of Bcl-2 to Bax. PMID:15052673

  20. [Effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1]. (United States)

    Chong, Tie; Niu, Jian-Qiang; Wang, Zi-Ming; She, Jun-Jun; Huang, Chen


    To observe the effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1 in vitro, and to explore its mechanism. The human renal cell carcinoma cell line GRC-1 was treated with matrine of different concentrations for 24, 48, 72 and 96 h respectively. The MTT assay was used to evaluate the cytotoxic effects of matrine on GRC-1 cells. The transmission electron microscope and flow cytometry were utilized to observe and detect the apoptosis of GRC-1 cells induced by matrine. The expression levels of Bcl-2 and Bax proteins were evaluated by streptavidin-biotin-peroxidase method. The matrine of different concentrations all have cytotoxic effects on GRC-1 cells, with obvious dose- and time-dependent effects. The apoptosis induced by matrine was confirmed in GRC-1 cells. With intervention of matrine (1.5 g/L) for 12 h, the expression level of Bcl-2 in GRC-1 cells was decreased while the expression level of Bax was increased as compared with those in the untreated group. The proliferation-inhibiting effects of matrine on human renal cell carcinoma cell line GRC-1 may be related to down-regulating the ratio of Bcl-2/Bax protein expression and promoting the apoptosis.

  1. Hydrophobic binding properties of bovine gallbladder mucin. (United States)

    Smith, B F; LaMont, J T


    Hydrophobic binding properties of purified bovine gallbladder mucin were studied by fluorescence spectroscopy using 1-anilino-8-naphthalene sulfonate (ANS) and N-phenyl-1-naphthylamine. The purified glycoprotein contained 75.5%, dry weight, as carbohydrate, 16.3% as protein, and 3.7% as sulfate; Mr = 2.2 X 10(6) was estimated by chromatography on Sephacryl S-500. Mucin contained a large number of low-affinity binding sites for these hydrophobic ligands. The dissociation constant, KD of mucin-ANS binding was 2.7 X 10(-5); each mucin molecule had approximately 42 binding sites for ANS. These binding sites were deduced to be on the unglycosylated portion of the protein core, as Pronase digestion completely eliminated binding. Reduction of mucin with 2-mercaptoethanol increased the fluorescence yield by formation of subunits with increased binding sites for the ligand. Increasing NaCl concentration (0.125 to 2.0 M) and decreasing pH (9 to 3) progressively increased fluorescence with the charged ligand ANS, suggesting that the binding site may have acidic groups which are shielded at high ionic strength or low pH. The fluorescent yield with N-phenyl-1-naphthylamine, an uncharged ligand, was an order of magnitude higher than with ANS. Bilirubin and bromosulfophthalein inhibited mucin-induced ANS fluorescence, but bile acids did not. Gallbladder mucin contains hydrophobic binding domains in the nonglycosylated peptide core that are involved in polymer formation and binding of biliary lipids and pigment.

  2. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients. (United States)

    Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich; Männel, Daniela N; Klein, Christoph A


    Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  3. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Magaldi, Thomas G.; Almstead, Laura L. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Bellone, Stefania [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Prevatt, Edward G. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Santin, Alessandro D. [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States); DiMaio, Daniel, E-mail: [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040 (United States); Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States)


    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  4. Primary hydatid cyst of the gallbladder: an unusual localization ...

    African Journals Online (AJOL)

    Primary hydatid cyst of the gallbladder: an unusual localization diagnosed by Magnetic Resonance Imaging (MRI). Rabii Noomene, Anis Ben Maamer, Ahmed Bouhafa, Noomen Haoues, Abdelaziz Oueslati, Abderraouf Cherif ...

  5. Exposure to Mold Toxin Linked to Gallbladder Cancer Risk (United States)

    A study by the National Cancer Institute reports an association between a marker of exposure to aflatoxin, a poisonous chemical produced by a type of mold, and gallbladder cancer in a population of men and women in Shanghai, China.

  6. Short Report: Beware the left-sided gallbladder | Alharthi | South ...

    African Journals Online (AJOL)

    Abstract. A left-sided gallbladder is a rare biliary anomaly with a prevalence of 0.2%. Its identification is important because of the numerous and potentially hazardous associated biliary and vascular anomalies that may be encountered during surgery.

  7. [Adenomyomatosis of the gallbladder the analysis of 328 operating cases]. (United States)

    Il'chenko, A A; Orlova, Iu N; Bystrovskaia, E V; Vasnev, E V; Khomeriki, S G; Vorob'eva, N N


    Adenomyomatosis (AMM) is related to the group of hyperplastic cholecystosis. Despite a long history of studying the problem, many questions concerning the etiology, pathogenesis, prevalence, tactics, management and treatment remain unsolved. To set the frequency of the AMM, its types, nature of pathological changes in the wall and lumen of gallbladder on the base of analizing the gallbladders after surgical removal. ultrasound examination, macro--and microscopic evaluation of 328 cases of the AMM gallbladders. According to ultrasound examination detection rate of AMM was 16.6%, and aacording to the study of surgical material--33%. The average age of patients 53 years old, male to female ratio--1:3,7. In 193 cases, the AMM was combined with concrements in gallbladder, in 70 cases the AMM was combined with polyps, among them in 40 patients the polyps were combined with concrements. In 175 patients we visualy analyzed the compaund of stones in gallbladder, in 112 cases there were the cholesterol stones (64%), in 51 cases--pigment stones (29.1%), in 12 patients (6.9%)--mixed. In some cases, was mentioned a combination of different AMM forms: adenomyoma on the background of diffuse adenomiomatosis--3.3%, diffuse form of AMM with more emphasized segmental lesions in one of the parts of gallbladder--6.1%, adenomyoma in one part combined with segmental lesions of another part of the gallbladder in 1.2% cases. In 64.9% cases, the AMM was combined with lipomatosis, in 56.7% cases--with the cholesterosis. The AMM is not a rare disease of gallbladder, and according to the histological examination of surgical material is detected in 31% of cases, and is oftenly combined with other types of hyperplastic cholecystosis.

  8. Volvo da vesícula biliar Gallbladder volvulus

    Directory of Open Access Journals (Sweden)

    Luiz Antonio Rodrigues


    Full Text Available A case of torsion of the gallbladder is presented. This is a rare condition that occurs when it is associated with anatomical variants related to abnormal fixation of the gallbladder to the liver bed. The blood irrigation is insufficient and the gallbladder develops necrosis. The abnormal implantation occurs in 4% of the population. If the gallbladder losses its fixations to the inferior margin of the liver with the presence of a 1011.g mesocyst a torsion can occur when this gallbladder twists axially with subsequent occlusion of the blood flow. The signs and symptoms are similar to those of severe acute cholecystitis: abrupt onset of the pain and large palpable mass below the right costal margin. The ultrasound can show a very large and anteriorly floating gallbladder: In this case, the ultrasound did not show any abnormal signs, so it is usually diagnosed at laparotomy and the treatement consists of cholecystectomy. This condition should be suspected in acute abdominal pain of unknown origin.

  9. Primary hydatid cyst of the gallbladder: a case report

    Directory of Open Access Journals (Sweden)

    Spahija Gazmend


    Full Text Available Abstract Introduction Echinococcosis, or hydatid disease, is endemic in some regions of the world, and has been a common pathology of surgical wards in Kosovo. Primary hydatid cyst of the gallbladder is an unusual and very rare localization of hydatid disease. So far, only five cases that fulfill the criteria of primary gallbladder hydatidosis have been published in the English medical literature. Case presentation We report a case of a 39-year-old Kosovan Albanian woman referred to the Abdominal Surgery Division of the University Clinical Center of Kosovo for "a calcified hydatid cyst of the liver with gallbladder involvement". Her history was significant for chronic right upper quadrant pain, characterized as intermittently colicky pain, accompanied by nausea. The patient underwent right subcostal laparotomy. Intra-operatively, a calcified primary hydatid cyst of the gallbladder was found. Its pericyst was tightly attached to the liver. Complete pericystectomy with cholecystectomy followed. The histopathology confirmed the presence of calcified hydatid cyst of the gallbladder, and that the cyst had developed entirely extra-mucosally. Five year follow-up showed no recurrence of disease. Conclusion Primary hydatid cyst of the gallbladder is a very rare clinical entity. Accurate preoperative diagnostic localization is not always easy, particularly in centers with limited diagnostic tools.

  10. Heterotopic pancreatic tissue obstructing the gallbladder neck: a case report. (United States)

    Weppner, Justin L; Wilson, Matthew R; Ricca, Robert; Lucha, Paul A


    Heterotopic pancreatic tissue is defined as pancreatic tissue outside the boundaries of the pancreas that has neither anatomic nor vascular continuity with the pancreas. Heterotopic pancreatic tissue in the gallbladder is uncommon and has rarely been reported to cause symptoms. We report a case of heterotopic pancreatic tissue obstructing the gallbladder neck resulting in cholecystitis. A 26-year-old female presented with right upper quadrant abdominal pain and fever. On physical examination the right upper quadrant was tender to palpation with a positive Murphy's sign. Laboratory tests were significant for elevated aspartate aminotransferase and alanine aminotransferase. Transabdominal sonography showed gallbladder wall thickening, a positive sonographic Murphy's sign, and an apparent large non-mobile stone at the gallbladder neck. Pathologic examination revealed cholecystitis but instead of a large stone there was a tan-yellow necrotic mass at the gallbladder neck. Microscopically, the mass consisted of heterotopic pancreatic tissue containing exocrine pancreatic acini, ducts, and islets of Langerhans. The final diagnosis was acute cholecystitis secondary to obstruction by heterotopic pancreatic tissue. Although heterotopic pancreatic tissue is usually an incidental finding on pathologic exam, one should not exclude it in the differential diagnosis of symptomatic gallbladder disease of indefinite etiology.

  11. Primary Gallbladder Small Lymphocytic Lymphoma as a Rare Postcholecystectomy Finding

    Directory of Open Access Journals (Sweden)

    Kyriakos Psarras


    Full Text Available Introduction. Primary lymphoma of the gallbladder is an extremely rare entity with approximately 50 cases reported so far. In many of these cases the presenting symptoms were mimicking symptomatic gallstone disease and the diagnosis was made postoperatively, especially when the preoperative imaging results were far from suspicious for malignant disease. Patients and Methods. We report a case of primary lymphoma of the gallbladder in an 85-year-old man with gallstone disease, who was admitted for elective cholecystectomy 2 months after an episode of acute cholecystitis and pancreatitis. Histological evaluation of the specimen revealed a small lymphocytic lymphoma of the gallbladder. This type of primary gallbladder lymphoma has not been previously reported. Discussion. The most common primary lymphomas of the gallbladder are MALT lymphomas and diffuse large B-cell lymphomas, although a variety of other histological types have been reported. The association of these lesions with chronic inflammation is the most convincing theory for their pathogenesis. For lesions confined to the gallbladder, cholecystectomy is considered to be sufficient, while supplementary chemotherapy significantly improves prognosis in more advanced disease.

  12. CHD1L Protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival

    Directory of Open Access Journals (Sweden)

    He Wei-Peng


    Full Text Available Abstract Background Our recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure. Methods In this study, immunohistochemistry (IHC for CHD1L was performed on a tissue microarray (TMA containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis. Receiver-operator curve (ROC analysis was used to evaluate patients’ survival status. Results There is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (PP PP Conclusions These findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma.

  13. Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells. (United States)

    Liu, Yongchen; Wang, Zheng; Li, Maolan; Ye, Yuanyuan; Xu, Yi; Zhang, Yichi; Yuan, Ruiyan; Jin, Yunpeng; Hao, Yajuan; Jiang, Lin; Hu, Yunping; Chen, Shili; Liu, Fatao; Zhang, Yijian; Wu, Wenguang; Liu, Yingbin


    Metformin is the most commonly used drug for type 2 diabetes and has potential benefit in treating and preventing cancer. Previous studies indicated that membrane proteins can affect the antineoplastic effects of metformin and may be crucial in the field of cancer research. However, the antineoplastic effects of metformin and its mechanism in gallbladder cancer (GBC) remain largely unknown. In this study, the effects of metformin on GBC cell proliferation and viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay and an apoptosis assay. Western blotting was performed to investigate related signaling pathways. Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (CLIC1) can affect GBC resistance in the presence of metformin. Our data demonstrated that metformin apparently inhibits the proliferation and viability of GBC cells. Metformin promoted cell apoptosis and increased the number of early apoptotic cells. We found that metformin can exert growth-suppressive effects on these cell lines via inhibition of p-Akt activity and the Bcl-2 family. Notably, either dysfunction or downregulation of CLIC1 can partially decrease the antineoplastic effects of metformin while upregulation of CLIC1 can increase drug sensitivity. Our findings provide experimental evidence for using metformin as an antitumor treatment for gallbladder carcinoma. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Morphological changes in the enteric nervous system caused by carcinoma of the human large intestine.

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    Janusz Godlewski


    Full Text Available The innervations of the large intestine is responsible for it peristalsis and contractibility. Investigations of the enteric nervous system in many colon diseases have revealed changes in this structure. No study has been carried out on morphological changes of the enteric nervous system in the human large intestine with carcinoma. The aim of this study was to investigate potential changes in the structure of the enteric neurons in patients with sigmoid and rectal cancer. Material for the study was obtained from patients undergoing operations due to carcinoma of the sigmoid colon and rectum. Microscopic observation of the cancerous tumor of the human large intestine revealed changes in the enteric nervous system innervating this part of the gastrointestinal tract. In the region of the enteric plexuses located close to the tumour, disruption of their correct placement and structure was observed. The changes also consisted of the disappearance of neurons and nerve fibers forming these plexuses. In the solid cancerous tumour, elements of the enteric nervous system were not present. Destruction of the enteric nervous system in the course of carcinoma of the large intestine may cause disruption of proper intestinal function and may be responsible for part of symptoms which the patients suffer.

  15. An in vivo cytogenetic analysis of human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Abhimanyu Mohanta


    Full Text Available Background: Oral cancer ranks in the top three of all cancers in India, which accounts for over 30% of all cancers reported in the country. The micronucleus test (MNT is one of the most widely applied short term tests used in genetic toxicology to evaluate the mutagenicity and carcinogenicity. Aims: The present study aims at an in vivo cytogenetic analysis of human oral squamous cell carcinoma and to assess the applicability of MNT in diagnosing early detection of oral carcinoma. Materials and Methods: Exfoliated scrape smears were collected from the clinically diagnosed 136 patients suffering from oral precancerous and cancerous lesions. The wet fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. Results: The frequency of micronucleated cells has been observed to be in increasing order with the increase of the age-groups and from control to precancerous to cancerous cases significantly in both sexes. Conclusion: Micronucleus formation in the oral mucosa could be a biomarker of genetic damage and also a potential onco-indicator in the long run of oral carcinogenesis. Therefore, MNT can be applied for the early detection of oral carcinoma in the human being.

  16. Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hanhui [Shanghai Medical College of Fudan University, Shanghai 200032 (China); Zhao, Wenrong [Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011 (China); Yang, Dan, E-mail: [Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai 200040 (China)


    Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

  17. Prevalence of Escherichia coli O157:H7 in Gallbladders of Beef Cattle▿ †


    Reinstein, S.; Fox, J. T.; Shi, X.; Nagaraja, T. G.


    Gallbladders and rectal contents were collected from cattle (n = 933) at slaughter to determine whether the gallbladder harbors Escherichia coli O157:H7. Both gallbladder mucosal swabs and homogenized mucosal tissues were used for isolation. Only five gallbladders (0.54%) were positive for E. coli O157:H7. Fecal prevalence averaged 7.1%; however, none of the cattle that had E. coli O157:H7 in the gallbladder was positive for E. coli O157:H7 in feces. Therefore, the gallbladder does not appear...

  18. Cytotoxicity of Thymus vulgaris essential oil towards human oral cavity squamous cell carcinoma. (United States)

    Sertel, Serkan; Eichhorn, Tolga; Plinkert, Peter K; Efferth, Thomas


    Oral cavity squamous cell carcinoma (OCSCC) accounts for 2% to 3% of all malignancies and has a high mortality rate. The majority of anticancer drugs are of natural origin. However, it is unknown whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic towards head and neck squamous cell carcinoma (HNSCC). Cytotoxicity of thyme essential oil was investigated on the HNSCC cell line, UMSCC1. The IC₅₀ of thyme essential oil extract was 369 μg/ml. Moreover, we performed pharmacogenomics analyses. Genes involved in the cell cycle, cell death and cancer were involved in the cytotoxic activity of thyme essential oil at the transcriptional level. The three most significantly regulated pathways by thyme essential oil were interferon signaling, N-glycan biosynthesis and extracellular signal-regulated kinase 5 (ERK5) signaling. Thyme essential oil inhibits human HNSCC cell growth. Based on pharmacogenomic approaches, novel insights into the molecular mode of anticancer activity of thyme are presented.

  19. [A PTHrP-producing cell line derived from human small cell lung carcinoma]. (United States)

    Iguchi, H


    We established a cell line, designated MS-1, from pleural effusion of a 54-yrs-old male patient with small cell lung carcinoma. MS-1 cells grew as a floating in RPMI-1640 medium supplemented with 10% FBS and the population doubling time was 45 hours. The chromosome number ranged from 49 to 52 and structural abnormalities of 1p+, 3q-, 6p-, 14p+ and 17p+ were observed in all the cells examined. MS-1 cells released PTHrP into the conditioned medium and heterogeneity of the PTHrP molecule produced in the cells was found in the gel permeation chromatography. Expression of the PTHrP gene as well as presence of the PTHrP protein in the cells were confirmed by reverse-transcriptase PCR(RT-PCR) and immunohistochemical staining. These findings indicate that MS-1 cells are derived from human small cell lung carcinoma, which produce PTHrP.


    Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano


    Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

  1. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas. (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas


    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro

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    Leith, J.T.; Dexter, D.L.; DeWyngaert, J.K.; Zeman, E.M.; Chu, M.Y.; Calabresi, P.; Glicksman, A.S.


    The responses of two heterogeneous human cancer cell lines and their derivative clones to graded single doses of X-rays were examined in vitro. One system consisted of the human colon carcinoma line DLD-1 and two subpopulations (clones A and D). The second system consisted of the human lung carcinoma line (LX1) and four subpopulations (LX1-1, LX1-2, LX1-3, and LX1-9). These subpopulations have previously been shown to be markedly heterogeneous in terms of such characteristics as karyotype, morphology, drug sensitivity, tumorigenicity, and expression of membrane glycoproteins (such as carcinoembryonic antigen and tumor colonic mucoprotein antigen). Exponentially growing cultures were irradiated with graded single doses of 100-kVp X-rays. Survival was assessed using colony formation as the end point, and responses from multiple experiments were fitted to the single-hit, multitarget equation of cell survival. Values for the mean lethal dose (D0, grays), quasithreshold dose (Dq, grays), and extrapolation number (n) were obtained. For the human colon adenocarcinoma system, these values for the three tumor lines were: DLD-1, 0.95, 2.34, and 11.7; clone A, 1.06, 2.23 and 8.20; and clone D, 1.08, 1.89, and 5.80. For the human lung carcinoma system, these values for the five sublines were: LX1, 1.14, 0.19, and 1.20; LX1-1, 0.96, 2.06, and 8.54; LX1-2, 0.98, 0.88, and 2.48; LX1-3, 0.68, 2.05, and 20.3; and LX1-9, 1.12, 0.00, and 1.00. These two human tumor systems therefore exhibit variability in their intrinsic sensitivity to X-irradiation. The data indicate that failure of some human carcinomas to respond to physical treatment modalities can be due to preexisting resistant subpopulations.

  3. Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells. (United States)

    Kang, Seo-Hee; Kim, Yon-Suk; Kim, Eun-Kyung; Hwang, Jin-Woo; Jeong, Jae-Hyun; Dong, Xin; Lee, Jae-Woong; Moon, Sang-Ho; Jeon, Byong-Tae; Park, Pyo-Jam


    Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

  4. Unexpected Uptake by the Gallbladder in Post-Ablative I-131 Scan

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    Kemal Ünal


    Full Text Available A 47-year-old woman was diagnosed as papillary thyroid carcinoma. I-131 ablation therapy was applied following total thyroidectomy, and the whole-body scan revealed a focus of increased uptake in the right upper quadrant. Lateral view images of the uptake site showed that the focus was located near the right liver lobe. The patient was referred to radiology department for correlative abdominal Computed Tomography (CT and Ultrasonography (US to rule out a possible liver metastasis. CT images detected a gallstone in the corresponding area, which was verified by US. These methods did not reveal any metastatic disease in the liver or in other abdominal organs. This is the first published case report documents a rare false-positive finding of I-131 scan that was associated with an asymptomatic gallstone, and emphasizes the importance of correlative imaging in gallbladder related I-131 uptake.

  5. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

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    Phadke, Manali; Krynetskaia, Natalia [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Mishra, Anurag [Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Krynetskiy, Evgeny, E-mail: [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States)


    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  6. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

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    San-Yuan Chen


    Full Text Available Oral squamous cell carcinoma (OSCC, an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL, a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  7. Harmonic ultrasonography for the detection of microlithiasis in the gallbladder

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    Choi, Chul Soon; Ku, You Jin; Yoon, Dae Young; Yun, Eun Joo; Seo, Young Lan; Lim, Kyoung Ja; Beak, Sora; Bae, Sang Hoon; Nam, Eun Sook [Kangdong Scared Heart Hospition, Hallym University College of Medicine, Seoul (Korea, Republic of)


    To validate the use of harmonic ultrasonography (US) in the detection of gallbladder microlithiasis. From November 30, 2012, to January 18, 2014, fundamental US (FUS) and harmonic US with a high background noise (HUS-N) were performed for evaluation of gallbladder during the routine abdomen US. During the US, a dot-like stone (or stones) with Brownian motion was regarded as a positive finding of microlithiasis. Fifty-five patients with microlithiasis in the gallbladder detected on US were enrolled as the subjects of a retrospective review. With respect to the obtained images, two abdominal radiologists independently scored the conspicuity of gallbladder microlithiasis on FUS and HUS-N by using a 4-grade scale. The statistical analysis employed a kappa test and a Wilcoxon rank-sum test. For FUS, the conspicuity grades of gallbladder microlithiasis were G1 in 25 and 37, G2 in 21 and 9, G3 in 6 and 6, G4 in 3 and 3 patients, while HUS-N showed G1 in 0 and 0, G2 in 3 and 2, G3 in 12 and 15, and G4 in 40 and 38 patients, respectively, by each of the two radiologists. The kappa value was 0.633 for FUS between the two radiologists and 0.708 for HUS-N. HUS-N showed better conspicuity of gallbladder microlithiasis than FUS with significant P-values of less than 0.001 and 0.001 for the two radiologists, respectively. Compared with FUS, HUS-N enables better detection of microlithiasis in the gallbladder.

  8. High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas. (United States)

    Larque, Ana B; Hakim, Sofia; Ordi, Jaume; Nadal, Alfons; Diaz, Alba; del Pino, Marta; Marimon, Lorena; Alobid, Isam; Cardesa, Antonio; Alos, Llucia


    It has been reported that high-risk human papillomavirus (HPV) is a causative agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of the transcriptionally active HPV has been proved through the identification of HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess the HPV-active transcription in a series of sinonasal carcinomas, in correlation with the HPV DNA identification and the p16 immunohistochemistry. Seventy patients with squamous cell carcinomas of the sinonasal tract were included in the survey. The main clinicopathological characteristics were recorded. All tumors were investigated for HPV through the HPV DNA detection by PCR, using the SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases. Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and one HPV35. In situ hybridization showed a dotted nuclear positivity in all these cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong, diffuse positivity for p16 was observed only in the HPV-positive cases. The 14 HPV-positive squamous cell carcinomas were non-keratinizing or scarcely keratinizing tumors. No significant differences were found in terms of gender, age, or staging at diagnosis between HPV-positive and HPV-negative tumors. However, differences in disease-free survival and overall survival between both groups of patients were significant (P=0.004 and P=0.028, respectively). In conclusion, we have shown that HPV is the etiological agent of a subset of sinonasal carcinomas demonstrating the transcriptionally active HPV in these tumors. Immunostaining for p16 can be used as a surrogate marker to identify these tumors.

  9. Role of Human Papillomavirus in Penile Carcinomas Worldwide. (United States)

    Alemany, Laia; Cubilla, Antonio; Halec, Gordana; Kasamatsu, Elena; Quirós, Beatriz; Masferrer, Emili; Tous, Sara; Lloveras, Belén; Hernández-Suarez, Gustavo; Lonsdale, Ray; Tinoco, Leopoldo; Alejo, Maria; Alvarado-Cabrero, Isabel; Laco, Jan; Guimerà, Nuria; Poblet, Enrique; Lombardi, Luis E; Bergeron, Christine; Clavero, Omar; Shin, Hai-Rim; Ferrera, Annabelle; Felix, Ana; Germar, Julieta; Mandys, Vaclav; Clavel, Christine; Tzardi, Maria; Pons, Luis E; Wain, Vincent; Cruz, Eugenia; Molina, Carla; Mota, Jose D; Jach, Robert; Velasco, Julio; Carrilho, Carla; López-Revilla, Ruben; Goodman, Marc T; Quint, Wim G; Castellsagué, Xavier; Bravo, Ignacio; Pawlita, Michael; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia


    Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. HPV DNA prevalence and type distributions were estimated. HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV

  10. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice. (United States)

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F; Diana, Michele; Pessaux, Patrick; Robinet, Eric


    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.

  11. Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile (United States)

    Aguayo, F; Castillo, A; Koriyama, C; Higashi, M; Itoh, T; Capetillo, M; Shuyama, K; Corvalan, A; Eizuru, Y; Akiba, S


    The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356–609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis. PMID:17579626

  12. Oncogenic PIK3CA Mutation and Dysregulation in Human Salivary Duct Carcinoma

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    Wanglong Qiu


    Full Text Available Salivary duct carcinoma (SDC is an aggressive malignant tumor with a high mortality, which resembles high-grade breast ductal carcinoma in morphology. The parotid gland is the most common location. Its molecular genetic characteristics remain largely unknown. We have previously reported high incidence of PIK3CA somatic mutations in head and neck squamous cell carcinoma, particularly in pharyngeal cancers. Here we examined the PIK3CA gene expression status and hotspot mutations in six cases of SDC by immunohistochemistry and genomic DNA sequencing. Immunohistochemistry showed that PIK3CA expression was elevated in all six patients with SDC. By DNA sequencing, two hotspot mutations of the PIK3CA gene, E545K (exon 9 and H1047R (exon 20, were identified in two of the six cases. Our results support that oncogenic PIK3CA is upregulated and frequently mutated in human SDC, adding evidence that PIK3CA oncogenic pathway is critical in the tumorigenesis of SDC, and may be a plausible drug target for this rare disease.

  13. Concurrent Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx in a Married Couple

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    Tyler D. Brobst


    Full Text Available Background. Although alcohol and tobacco use are known risk factors for development of squamous cell carcinoma in the head and neck, human papillomavirus (HPV has been increasingly associated with this group of cancers. We describe the case of a married couple who presented with HPV-positive oropharynx squamous cell carcinoma within two months of each other. Methods. Tumor biopsies were positive for p16 and high-risk HPV in both patients. Sanger sequencing showed a nearly identical HPV16 strain in both patients. Both patients received chemoradiation, and one patient also underwent transoral robotic tongue base resection with bilateral neck dissection. Results. Both patients showed no evidence of recurrent disease on follow-up PET imaging. Conclusions. New head and neck symptoms should be promptly evaluated in the partner of a patient with known HPV-positive oropharynx cancer. This case expands the limited current literature on concurrent presentation of HPV-positive oropharynx squamous cell carcinoma in couples.

  14. Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue (United States)

    Hosseini, Seyed Zinab; Makvandi, Manoochehr; Samarbafzade, Alireza; Timori, Ali; Ranjbar, Nastaran; Saki, Nader; Nisi, Nilofar; Shahani, Toran; Varnaseri, Mehran; Ahmadi, Kambiz Angali


    Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 µm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression. PMID:28545184

  15. Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas

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    Greiner, J.W.; Smalley, R.V.; Borden, E.C.; Martin, E.W.; Guadagni, F.; Roselli, M.; Schlom, J. (Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States))


    Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN-gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma. 15 references.

  16. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma? (United States)

    Näsman, Anders; Nordfors, Cecilia; Holzhauser, Stefan; Vlastos, Andrea; Tertipis, Nikolaos; Hammar, Ulf; Hammarstedt-Nordenvall, Lalle; Marklund, Linda; Munck-Wikland, Eva; Ramqvist, Torbjörn; Bottai, Matteo; Dalianis, Tina


    To investigate whether the rise during the past decades in the incidence of tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and the proportion of human papillomavirus (HPV) positive cancer has continued in Stockholm. Pre-treatment biopsies (n=252) available from 280 patients diagnosed with TSCC and BOTSCC during 2008-2012 in the County of Stockholm were tested for HPV DNA by a multiplex bead-based assay. Incidence records were acquired from the Swedish Cancer Registry. The data obtained were evaluated together with previous figures from 1970 to 2007. HPV DNA was present in 186/252 (74%) of TSCC and BOTSCC biopsies obtained during 2008-2012 in Stockholm. In this region the age-standardised incidence, including the prevalence of HPV-positive and HPV-negative TSCC stabilised 2007-2012 compared to 2000-2006, while for BOTSCC throughout 1998-2012 the same parameters increased moderately (p<0.05, for all). In parallel, from 2000 to 2006 through 2007-2012 in Sweden, the age-standardised incidence of both TSCC and BOTSCC continued to rise (p=0.012 and p=0.001 respectively). During 2000-2012 the age-standardised incidence and the proportion of HPV-positive TSCC have stabilised at a high level, while the proportion of HPV-negative cancer has remained at a low level in Stockholm, whereas for BOTSCC all parameters are increasing moderately. In contrast, in Sweden the incidence of both TSCC and BOTSCC is still increasing. We hypothesise that the HPV epidemic could be stabilising, first for TSCC, but so far not for BOTSCC, in e.g. some urban areas, while previous trends for both tumours persist at other geographic locations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells

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    Laihia Jarmo K


    Full Text Available Abstract Background cis-urocanic acid (cis-UCA is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells. Methods 5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p Results Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases. Conclusions Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.

  18. Pain patterns after distension of the gallbladder in patients with acute cholecystitis

    DEFF Research Database (Denmark)

    Middelfart, H V; Jensen, P; Højgaard, L


    and the cystic duct opening pressure. METHODS: Twelve patients (nine women, three men) treated with cholecystostomy for acute cholecystitis were investigated. Simultaneous cholescintigraphy and measurement of changes in intraluminal gallbladder pressure after injections of saline through a gallbladder catheter...

  19. The presence and prognostic significance of human papillomavirus in squamous cell carcinoma of the larynx. (United States)

    Erkul, Evren; Yilmaz, Ismail; Narli, Gizem; Babayigit, Mustafa Alparslan; Gungor, Atila; Demirel, Dilaver


    The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively. Five test samples were excluded from the study due to inadequate deoxyribonucleic acid purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal squamous cell carcinoma. Human papilloma virus genotyping revealed double human papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases. Although HPV-positive cases showed slightly better 3 years survival than HPV-negative ones, this finding was not statistically significant (overall survival p = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p = 0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not significantly associated with any clinicopathological features (p > 0.05). Among 73 patients, only 4 had an immunohistochemical staining of p16 and these patients were also HPV DNA 16 positive. Although our study results revealed a slightly better survival in patients with HPV DNA positivity for HPV 16 compared to the negative ones, the difference was not statistically significant. However, an increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal squamous cell carcinoma by RT-PCR method was observed compared to our previous study. Although the presence of HPV in laryngeal SCCs seems to be associated with slightly better

  20. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li Fan


    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  1. [Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma]. (United States)

    Fan, Bing-Lin; Zhu, Wu-Ling; Zou, Guo-Lin; Luo, Guo-Sheng; Xu, Chun-Lei; Zhao, Wei-Xing


    Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.

  2. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda


    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  3. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chen YJ


    Full Text Available Yu-Jen Chen,1–4 Chien-Chih Chen,5 Huey-Lan Huang6 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Biotechnology, HungKuang University, Taichung, 6Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan Abstract: Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In

  4. Motilin and gallbladder: new dimensions in gastrointestinal physiology. (United States)

    Suzuki, T; Takahashi, I; Itoh, Z


    Intravenous infusion of motilin (0.3-0.9 micrograms/kg-hr) during the interdigestive state induced a transient but strong tonic contraction in the gallbladder, which was similar to the natural interdigestive gallbladder contraction, as well as a typical IMC in the stomach and the duodenum. This motilin-induced contraction always occurred simultaneously with the intitiation of phase II contractions of the IMC in the duodenum. The increase in contractile force (11.5 +/- 0.57 g) was not related to the dose of motilin tested. In contrast, intravenous infusion of CCK-octapeptide (CCK-OP, 0.03-0.09 micrograms/kg-hr) induced a dose related tonic contraction (7.8 +/- 0.41-17-7 +/- 0.77 g) which lasted as long as the CCK-OP infusion continued during the interdigestive state. Atropine sulfate (0.025 mg/kg) strongly inhibited both motilin- and CCK-OP induced gallbladder contractions. The present study indicates that the canine gallbladder in the conscious state is responsive to at least two hormonal factors, motilin and CCK. The contractile response of the gallbladder to motilin is quite different from the response to CCK-OP. However, both responses are mediated at least partially by cholinergic pathways.

  5. Gallbladder benign neoplasms: relationship with lithiasis and cancer (ultrasonographic study). (United States)

    Brogna, A; Bucceri, A M; Branciforte, G; Travali, S; Loreno, M; Muratore, L A; Catalano, F


    The aim of this study is to clarify the prevalence of gallbladder benign neoplasms, their ultrasonographic appearance and their relationship with gallbladder lithiasis and cancer. This study was carried out on 9000 consecutive patients having ultrasound of upper abdomen. Only adenomas and papillomas are considered as true benign neoplasms of the gallbladder. Adenomiomatosis and cholesterol polyps, often erroneously labelled as benign neoplasms, were excluded. Patients were followed-up by ultrasound every three months up to two years. The prevalence of benign neoplasms was 1.19%. Papillomas were found more frequently than adenomas both in males (68.51%) and in females (94.33%). Gallstones were not concomitant with benign neoplasms in any case. Neither stones nor growth of gallbladder benign neoplasms were recorded within the two-year follow-up period. Papillomas were more frequent than adenomas. No gallstone was concurrent with gallbladder benign neoplasms in our series. However, when gallstones are evidenced at ultrasound, further attention is recommended to discover probable concomitant neoplasms. Papillomas and adenomas more than 1 cm in diameter should be quarterly followed-up, while smaller masses could be six-monthly controlled. Surgery should be indicated for large-sized or rapidly growing masses because of the risk for cancer development.

  6. Sonographic changes of liver and gallbladder in acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    Ebrahimi Daryani N


    Full Text Available Hepatomegaly, decrease in the liver paranchymal echo and increase in the gallbladder wall thickness has been shown in acute viral hepatitis. The present study was done to determine sonographic changes in acute viral hepatitis. We performed liver and bile ducts sonography and specific tests on 42 patients (mean age: 31.5 and 61% male with acute viral hepatitis. Gallbladder wall thickness was seen in 45.2% and hepatomegaly in 33.3% of patients and liver paranchymal echo was decreased in 19.3%. Age, sex, type of hepatitis, cholecystitis like symptoms, aspartate aminotransfrase, alanine aminotransfrase, alkaline phosphatase and bilirubin did not significantly corralate with these changes. Only raised prothrombin time was strongly correlated to the thickening of the gallbladder and decrease in the liver paranchymal echo and cholesistic like symptoms we can postulate that thickening of the gallbladder and decrease in the liver paranchymal echo is not dependent on the severity and speed of the paranchymal necrosis (as considered with ALT and AST but they depend on the liver function disturbance (as considered with PT because the thickening of the gall bladder is present in 45% of the patients and 10% of the normal population have gallbladder stones, one should not perform the diagnosis of acute cholecystitis, only on the basis of sonographic report without attention to the clinical and laboratory data.

  7. Pathophysiological significance of gallbladder volume changes in gallstone diseases (United States)

    Huang, Shing-Moo; Yao, Chung-Chin; Pan, Huichin; Hsiao, Kuang-Ming; Yu, Ji-Kuen; Lai, Te-Jen; Huang, Shueh-Ding


    AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients. METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student’s t tests were used. P acute cholecystitis gallbladders (84.66 ± 26.32 cm3, n = 12, vs 53.19 ± 33.80 cm3, n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm3 vs 6.77 ± 15.75 cm3, P acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones. PMID:20818819

  8. Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells. (United States)

    Wu, F; Hu, Y; Long, J; Zhou, Y J; Zhong, Y H; Liao, Z K; Liu, S Q; Zhou, F X; Zhou, Y F; Xie, C H


    TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

  9. High-risk HPVs and human carcinomas in the Syrian population

    Directory of Open Access Journals (Sweden)

    Ala-Eddin eAl Moustafa


    Full Text Available Human papillomavirus (HPV infection is the most common sexually transmitted infection; persistent infection with high-risk types of HPV present a major risk factor for the initiation and progression of a variety of human carcinomas including cervical, colorectal, head and neck as well as breast carcinomas. A huge number of studies investigated and reported the incidence of high-risk HPVs in these cancers worldwide particularly in the developed countries; therefore, two HPV prophylactic vaccines against the two most frequent high-risk HPV types (16 and 18 have been developed and used worldwide. However, there are very limited studies about the prevalence of HPVs in the developing countries especially in Africa and some states of the Middle East (ME. In this mini review, we outline the presence of high-risk HPVs in human cervical, colorectal, head and neck as well as breast cancers in the Syrian population, which was recently explored for the first time by a Canadian/Syrian group.

  10. Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

    Energy Technology Data Exchange (ETDEWEB)

    Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)


    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

  11. Establishment and characterization of a human primary prostate carcinoma cell line, HH870. (United States)

    Selvan, Senthamil R; Cornforth, Andrew N; Rao, Nagesh P; Reid, Yvonne A; Schiltz, Patric M; Liao, Ray P; Price, David T; Heinemann, F Scott; Dillman, Robert O


    Development of new therapeutic modalities for human prostate carcinoma has been impeded by a lack of adequate in vitro and in vivo models. Most in vitro studies have been carried out using a limited number of human prostate cancer cell lines that are mostly derived from metastatic tumors sites or are immortalized. Characterization of the prostate cancer cell line, HH870, included description of morphology, determination of doubling time, response to androgens, immunocytochemistry, and immunoblotting of proteins known to be associated with prostate carcinoma, karyotyping, fluorescence in situ hybridization (FISH), DNA profiling, and growth as xenograft in athymic rodents. HH870 expresses various epithelial marker antigens that correlate with known basic immunostaining profiles of prostate adenocarcinoma, although the cell line does not express PSA, PSMA, or PAP. HH870 exhibits complex chromosomal abnormalities and harbors no immortalizing HPV, BKV, JCV, and SV40 DNA. We report the successful establishment and characterization of a new long-term primary human prostate tumor cell line HH870. Copyright (c) 2004 Wiley-Liss, Inc.

  12. Talin-1 correlates with reduced invasion and migration in human hepatocellular carcinoma cells. (United States)

    Fang, Kun-Peng; Zhang, Jian-Lin; Ren, Yan-Hong; Qian, Ye-Ben


    Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell (LO2 cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and LO2 cell line (pmigration capabilities of the five cancer cell lines differed significantly (pmigration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

  13. Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration. (United States)

    Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi


    Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

  14. CT of gallbladder cancer and its mimics: a pattern-based approach. (United States)

    Deshmukh, Swati D; Johnson, Pamela T; Sheth, Sheila; Hruban, Ralph; Fishman, Elliot K


    On computed tomography (CT), gallbladder pathology may be detected incidentally or as the etiology of symptoms that prompted imaging. Accurate pathologic diagnosis can be challenging, however, due to overlapping appearances of malignant and benign gallbladder disease. This pictorial essay takes a pattern-based approach to CT of the gallbladder, to help the radiologist formulate the proper differential diagnosis.

  15. Pain patterns after distension of the gallbladder in patients with acute cholecystitis

    DEFF Research Database (Denmark)

    Middelfart, H V; Jensen, P; Højgaard, L


    of symptoms arising from the gallbladder and the underlying pathophysiology is therefore desirable. The aim of the present study was consequently primarily to characterize the symptom patterns after distension of the gallbladder. Secondary aims were to describe the pressure-volume relation in the gallbladder...

  16. Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients

    NARCIS (Netherlands)

    Stolk, M. F.; van Erpecum, K. J.; Peeters, T. L.; Samsom, M.; Smout, A. J.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.


    The role of interdigestive gallbladder emptying in gallstone formation is unknown. In fasting healthy subjects, gallbladder emptying is associated with antral phase III of the migrating motor complex (MMC) and high plasma motilin. Therefore, gallbladder volumes and motilin levels were measured

  17. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice. (United States)

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J


    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

  18. Parameters Derived from Integrated Nuclear Fluorescence, Syntactic Structure Analysis, and Vascularization in Human Lung Carcinomas

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    Klaus Kayser


    Full Text Available Combined measurements of integrated nuclear fluorescence (INF and vascularization were performed on surgical specimens of human lung carcinomas. Histological slides of formalin‐fixed, paraffin‐embedded tissue samples were treated with Texas Red‐labeled antibody to factor VIII and the fluorochrome DAPI. The resulting images were analyzed with an epi‐illumination fluorescence microscope and two different filter blocks. The first image displayed the vessels, and the second the DAPI‐stained nuclei of surrounding cells. The extent of vascularization was assessed by calculating the volume fraction (Vv, the surface fraction (Sv, the area, and the minimum diameter of the vessels. The INF was measured in tumour cells and lymphocytes, and was grouped according to the distance from the nearest vascular boundary into the intervals of 0–20, 21–40, 41–60, 61–80, and >80 μ. The numerical densities (Nv as well as the percentages of S‐phase‐related tumour cell fraction (SPRF and of tumour cells with an INF > 5C were computed. A minimum of 50 vessels and 300 tumour cells were examined. The material included 100 cases with primary lung carcinoma (39 epidermoid carcinomas, 39 adenocarcinomas, 13 large cell carcinomas, three small cell anaplastic carcinomas, and 6 carcinoid tumours. On the average, the volume density of the stroma amounts to 16.7%, and that of the vessels (Vv to 12.8%. The minimum diameter of the intratumoral vessels is 13 μ and the measured circumference 138 μ. The numerical densities of tumour cells (lymphocytes decrease with increasing distance from the vascular boundary from 6.3 (1.7 to 1.0 (0.1. A reduction is also seen in the percentage of the SPRF from 10.7 to 8.1%. The percentage of tumour cells with an INF > 5C, however, is positively correlated to the distance from the vascular surfaces from 34.2 to 38.2%. The measurements reveal that tumour cells are densely positioned and have an increased proportion of

  19. [Detection of acid mucins in gastric metaplasia of the gallbladder]. (United States)

    Buitrago Salassa, Carolina; Javier Lespi, Pablo


    In this paper we present a histological and histochemical study about the metaplastic changes in the gallbladder, and discussed the participation of the antral metaplasia in the genesis of gallbladder cancer. We collected 43 pieces of colecistectomy whit antral metaplasia, intestinal metaplasia and displasia. Presence of mucins were demonstrated by the alcian blue stain to ph 3 and ph 0.5 ph. We found sulphated and not sulphated acid mucins. In all of the forms of antral metaplasia. The not freguent finding coas an intense staining of intracitoplasmie mucins in metaplastic cells. We alsa detected small globular deposits in isolated cells of surface epithelium. This finding seems to associate antral metaplasia with intestinal metaplasia, at least in the mucins production. Antral metaplasia could be one of the first steps involved in the sequence displasia-cancer in the gallbladder.

  20. [Prokaryotic expression, purification and antigenicity identification of human renal cell carcinoma-associated antigen G250]. (United States)

    Xiao, Yi; Gao, Jiangping; Gao, Kun; Yan, Jinqi; Zhang, Liang; Wang, Yu; Xu, Yuanji; Wang, Wei; Wang, Xiaoxiong; Yu, Jiyun


    To amplify human renal cell carcinoma (RCC)-associated antigen G250 gene and construct a recombinant plasmid pET-42a-hG250, express and purify human G250 protein and identify its antigenicity. The gene of human G250 was amplified from pGEM-T-G250 by PCR. After sequencing, the PCR product (112-1242 bp) was cloned into pET-42a prokaryotic expression vector to construct the recombinant plasmid pET-42a-hG250. The plasmid was transformed into BL21 (DE3) and human G250 protein was expressed under the induction of IPTG. The fusion protein was purified and identified by SDS-PAGE, Western blotting and ELISA sequentially. The human G250 prokaryotic expression vector pET-42a-hG250 was successfully constructed as confirmed by enzyme digestion and DNA sequencing. After transformation into BL21 (DE3), the target protein was successfully induced to express and purified as expected. Western blotting and ELISA demonstrated that the purified human G250 protein had a desirable immunogenicity. The recombinant prokaryotic expression vector pET-42a-hG250 has been constructed successfully. The purified human G250 protein has a good antigenicity.

  1. Effects of Roundabout 5 on adhesion, invasion and potential motility of human tongue carcinoma Tb cells. (United States)

    Xiao, Rui; Zhao, Yuan; Wang, Li-jing; Li, Wei-ping


    Roundabout 5 (R5) is a monoclonal antibody which can neutralize the binding of Roundabout 1 (Robo1) to Slit2. Oral squamous cell carcinoma angiogenesis was significantly inhibited when R5 blocked slit-robo signaling pathway. However, the effect of R5 on the invasion of tongue cancer cells has not been investigated clearly. In this study, we treated human brain metastasis of tongue cancer cell lines (Tb cells) with R5 at different concentrations, and the control Tb cells were treated with 10 mg/ml immunoglobin G 2b (IgG2b). The effect of R5 on the proliferation, adhension, invasion and motility of Tb cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell attachment assay on fibronectin (FN), wound assay and chemotaxis assay, respectively. And gelatin-incorporated sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to investigate the activity of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). R5 had no effect on the proliferation of Tb cells. However, R5 could significantly inhibit the motility, attachment and chemotaxis of Tb cells to FN, and it could also significantly inhibit the activity of MMP2 and MMP9 in Tb cells. R5 can inhibit the adhesion, invasion and motility of human tongue carcinoma Tb cells.

  2. Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis. (United States)

    Wei, Ruojing; Zhu, Guodong; Jia, Ning; Yang, Wenzeng


    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, potentiating effect of EGCG on TRAIL-induced apoptosis human renal carcinoma cell line 786-O which is relatively resistant to TRAIL was examined, and the possible mechanism was investigated. Here, we show that co-treatment with EGCG and TRAIL induced significantly more profound apoptosis in 786-O cells. Treatment of 786-O cells with EGCG and TRAIL downregulated c-FLIP, Mcl-1, and Bcl-2 proteins in a caspase-dependent pathway. Moreover, we found that pretreatment with NAC markedly inhibited the expression levels of c-FLIP, Mcl-1, and Bcl-2 downregulated by the combinatory treatment, suggesting that the regulating effect of EGCG on these above apoptosis-relevant molecules was partially mediated by generation of ROS. Taken together, the present study demonstrates that EGCG sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis by downregulation of c-FLIP, Mcl-1, and Bcl-2.

  3. Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells. (United States)

    Zhang, Zhi-Dong; Liang, Kai; Li, Kun; Wang, Guo-Quan; Zhang, Ke-Wei; Cai, Lei; Zhai, Shui-Ting; Chou, Kuo-Chen


    Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has been widely used as a food supplement and reported to have antioxidant and anticancer properties. The current study was designed to assess the cytotoxic, apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. A549 cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at various concentrations (0-300 μg/ml) for 24 hr. The comet assay and γH2AX assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells. Chlorella vulgaris hot water extract induced apoptosis and DNA damage in human lung carcinoma cells. CGF can thus be considered a potential cytotoxic or genotoxic drug for treatment of lung carcinoma. Copyright© Bentham Science Publishers; For any queries, please email at

  4. Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

    Directory of Open Access Journals (Sweden)

    Dehelean Cristina A


    Full Text Available Abstract Background Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition. Results New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin (over 90%. Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma, A2780 (ovarian carcinoma, HeLa (cervix adenocarcinoma and MCF7 (breast adenocarcinoma, by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice. Conclusions The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

  5. Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

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    Ke-Hung Tsui


    Full Text Available Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN, N-myc downstream gene 1 (NDRG1, and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

  6. The enamel matrix derivative (Emdogain) enhances human tongue carcinoma cells gelatinase production, migration and metastasis formation. (United States)

    Laaksonen, Matti; Suojanen, Juho; Nurmenniemi, Sini; Läärä, Esa; Sorsa, Timo; Salo, Tuula


    Enamel matrix derivative Emdogain (EMD) is widely used in periodontal treatment to regenerate lost connective tissue and to improve the attachment of the teeth. Gelatinases (MMP-2 and -9) have an essential role in the promotion and progression of oral cancer growth and metastasis formation. We studied the effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and in vivo. In vitro, EMD (100 microg/ml and 200 microg/ml) remarkably induced the MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the transmigration of HSC-3 cells but had no effect on the HMK migration in transwell assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD, whereas it had only minor effect on the wound closure of HMKs. The migration of both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a limited effect on cell attachment to various extracellular matrix components. The in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft metastasis formation. Our results suggest that the use of EMD for patients with oral mucosal carcinomas or premalignant lesions should be carefully considered, possibly avoided.

  7. Value of gallbladder-preserving partial cholecystectomy in treatment of abnormal gallbladder morphology complicated by sand-like calculous cholecystitis: a reports of 18 cases

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    LIANG Fasheng


    Full Text Available Objective To investigate the value of laparoscopic gallbladder-preserving partial cholecystectomy in the treatment of abnormal gallbladder morphology complicated by sand-like calculous cholecystitis. Methods A total of 18 patients with abnormal gallbladder morphology complicated by sand-like calculous cholecystitis who underwent laparoscopic and choledochoscopic partial cholecystectomy in Dalian Friendship Hospital from July 2010 to January 2014 were enrolled. All the patients had abnormal gallbladder morphology manifested as folded gallbladder or adenomyosis, and the lesions were located in the distal end of the gallbladder. Before the surgery, gallbladder contraction test was performed for the diseased part and the normal part of the gallbladder to be preserved. During the surgery, choledochoscopy showed an unobstructed cystic duct and good elasticity in the gallbladder wall, and there was no marked chronic inflammation. After the diseased part of the gallbladder was removed, 4-0 absorbable suture was used for two-layer consecutive suture of the gallbladder. The t-test was used for comparison of continuous data between groups. Results All the patients underwent the surgery successfully. The mean time of operation was 98.0±9.0 minutes, and the mean time to first flatus was 22.8±2.5 hours. The patients were able to get out of the bed and drink water at 6 hours after surgery and to have meals at 24 hours after surgery. They fully recovered and were discharged at 5-7 days after surgery, and no patient experienced the complications such as bile leakage. The patients were followed up for 6-80 months; the patients′ preoperative clinical symptoms disappeared, and there was no recurrence of calculi. At 6-12 months after surgery, the patients experienced compensated cholecystectasis, and there was a significant increase in the mean volume of the gallbladder after surgery (30.29±4.23 cm3 vs 21.72±4.34 cm3, t=-13.00, P<0.001. There was a

  8. Gallbladder endometriosis as a cause of occult bleeding

    Institute of Scientific and Technical Information of China (English)

    K Saadat-Gilani; L Bechmann; A Frilling; G Gerken; A Canbay


    A 17-year-old girl with colicky abdominal pain and chronic anemia presented to the gastrointestinal service of the University Hospital of Essen. In the routine workup, there were no pathological findings despite the anemia. Because of the fluctuation of symptoms with a climax at the time of menstruation, consecutive ultrasound studies were performed revealing a visible mass inside the gallbladder. This finding was confirmed by a magnetic resonance imaging (MRI) study performed at the same time. Because of the severe anemia by that time, a cholecystectomy was performed, and histology reconfirmed the diagnosis of isolated gallbladder endometriosis. The patient recovered well and has had no recurrence of the disease to date.

  9. Rare bile duct anomaly: B3 duct draining to gallbladder

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    Seung Eun Lee


    Full Text Available A 10-year-old girl presented with recurrent right upper abdominal pain and dyspepsia. Magnetic resonance cholangiopancreatography revealed a dilated common channel of intrahepatic bile duct of segment 3 (B3 and segment 4 (B4 drained into the gallbladder directly. The patient underwent laparoscopic cholecystectomy and Roux-en Y hepaticojejunostomy (B3-jejunostomy. Among the anatomical variability of the biliary system, the cholecystohepatic ducts are controversial in existence and incidence. We report a very rare variant of a cholecystohepatic duct in which the B3 duct drained into gallbladder directly and to the best of our knowledge this is the first report.

  10. Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

    DEFF Research Database (Denmark)

    Bak, Martin; Teglbjaerg, P S


    Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation....... Intestinal pleomorphic carcinomas are histologically identical to pulmonary giant cell carcinomas. The prognosis is poor due to early tumor spread, with only a few months of postoperative survival. The pleomorphic carcinomas have some of the differentiation characteristics of carcinoid tumors and are best...

  11. COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma. (United States)

    Honjo, Soichiro; Kase, Satoru; Osaki, Mitsuhiko; Ardyanto, Tonang Dwi; Kaibara, Nobuaki; Ito, Hisao


    The expression of cyclooxygenase (COX)-2 is induced by growth factors, tumor promoters and cytokines, and is correlated with carcinogenesis, tumor progression and inhibition of apoptosis. To clarify the pathological significance of COX-2, we examined the effect of a selective COX-2 inhibitor, NS398, on two human gastric carcinoma cell lines, MKN-45 and KATO-III, and the expression of Skp2, P27/Kip1 and COX-2 protein in human gastric carcinomas. NS398 inhibited cell growth in a time- and dose-dependent manner and exerted cell cycle arrest in the G0/G1 phase without induction of apoptosis in MKN-45, but had no effect in KATO-III. In MKN-45, NS398 induced up-regulation of P27/Kip1 and down-regulation of COX-2, cyclin D1 and Skp2. Immunohistochemistry using 63 surgically resected gastric carcinomas disclosed that COX-2 expression was correlated with Skp2 expression and that P27/Kip1 expression was inversely correlated with COX-2 and Skp2 expression. High levels of COX-2 or Skp2 were significantly correlated with poor survival (P=0.02 and P=0.004). Our results suggested that: a) NS398 induced inhibition of cell proliferation through cell cycle arrest and suppressed the expression of Skp2 in COX-2-expressing gastric carcinoma cells, and b) COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas.

  12. Curcumin promotes the apoptosis of human endometrial carcinoma cells by downregulating the expression of androgen receptor through Wnt signal pathway. (United States)

    Feng, W; Yang, C X; Zhang, L; Fang, Y; Yan, M


    The current study aimed to explore the effect ofcurcumin on androgen receptor (AR) expression in endometrial carcinoma cells, as well as the underlying mechanisms. Endometrial carcinoma cells were treated with curcumin (10, 50, and 100 micromol/l) for 12, 24, and 48 hours. Their growth curves were drawn using MTT assays and their apoptotic rates were determined using flow cytometry. The mRNA and protein expression of AR was detected using PCR and that of the Wnt signal related nucleopro- tein beta-cantenin was observed using western blot analysis. The influence of beta-cantenin on the action of curcumin was observed. Curcumin downregulated the proliferation and apoptosis of human endometrial carcinoma cells in concentration and time-dependent manners. It downregulated the expression of AR and beta-cantenin in the cells. rWnt3a partially cancelled the effects of curcumin on the proliferation and apoptosis of human endometrial carcinoma cells as well as the AR expression-downregulating effect of curcumin. Curcumin inhibits the proliferation and apoptosis of human endometrial carcinoma cells by downregulating their AR expression through the Wnt signal pathway.

  13. NF-kappa B signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Wu, Xinxing


    The HDAC inhibitor Trichostatin A (TSA) exhibits antiturnour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113

  14. Expression of GLUT1 in stratified squamous epithelia and oral carcinoma from humans and rats

    DEFF Research Database (Denmark)

    Voldstedlund, M; Dabelsteen, Erik


    Most cells express facilitative glucose transporters. Four isoforms (GLUT1-4) transporting D-glucose across the plasma membrane show a specific tissue distribution, which is the basis for tissue-specific patterns in glucose metabolism. GLUT1 is expressed at high levels in tissue barriers...... such as the blood-brain barrier, and this isoform has been suggested as an indicator of such barriers. GLUT1 has been found in basal layers of human epidermis where no such tissue barrier is present. To further clarify these issues, we examined the distribution of GLUT1 and GLUT4 in skin, different types of oral...... mucosa from rat and man, and a human oral carcinoma by indirect immunofluorescence microscopy. The results showed that GLUT1 was expressed in the basal and parabasal layers of the different stratified squamous epithelia, with some variations between keratinized and non-keratinized subtypes. GLUT1...

  15. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

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    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.


    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  16. Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma. (United States)

    Zhang, Yi-Fan; Ho, Mitchell


    Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer.

  17. Abnormal expression of HAX-1 is associated with cellular proliferation and migration in human hypopharyngeal squamous cell carcinoma (United States)

    Wu, Hao; Chen, Jianqiu; Wang, Qiang; Yin, Yong; Da, Peng; Le, Huijun; Zhang, Zhenxin; Qiu, Xiaoxia


    HCLS1-associated protein X-1 (HAX-1) is highly expressed or overexpressed in various types of human tumor, and its overexpression is associated with cancer metastasis and cellular proliferation. However, the precise molecular mechanism involved in HAX-1-associated proliferation and metastasis in hypopharyngeal carcinoma is unknown. The present study aimed to investigate the role of HAX-1 in the metastasis and proliferation of hypopharyngeal carcinoma. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting indicated that HAX-1 was overexpressed in hypopharyngeal carcinoma specimens. MTT, clone formation and transwell assays were performed to detect the effects of HAX-1 knockdown or overexpression on the major oncogenic properties of the FaDu hypopharyngeal carcinoma cell line. Downregulation of HAX-1 was observed to significantly suppress cellular proliferation, migration and clonal. By contrast, overexpression of HAX-1 significantly promoted cellular proliferation, migration and clonal formation. Furthermore, HAX-1 knockdown markedly suppressed epithelial-mesenchymal transition. In conclusion, HAX-1 is a potential oncogene, and may promote the tumorigenesis and progression of hypopharyngeal carcinoma, as well as serve as a valuable molecular target for the treatment of hypopharyngeal carcinoma. PMID:28791389

  18. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2. (United States)

    Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen


    Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

  19. Human papillomavirus (HPV) status of non-tobacco related squamous cell carcinomas of the lateral tongue (United States)

    Poling, JS; Ma, X-J; Bui, S; Luo, Y; Li, R; Koch, WM; Westra, WH


    Objectives The human papillomavirus (HPV) is an important cause of some head and neck squamous cell carcinomas (HNSCCs), but its role in cancer of the lateral tongue is debatable. Suspicion of HPV causation is heightened when these lateral tongue carcinomas arise in patients that are young and/or have never smoked. The purpose of this study was to determine the incidence of transcriptionally active high risk HPV in these tumors, with a particular emphasis on non-smoking patients who are often presumed to have HPV-positive tumors. Methods We evaluated 78 HNSCCs of the lateral tongue for the presence of HPV using p16 immunohistochemistry and an RNA in situ hybridization assay targeting HPV E6/E7 mRNA. The study population was enriched for patients without traditional risk factors such as smoking and drinking. Results P16 overexpression was detected in 9 (11.5%) of 78 cases, but HPV E6/E7 mRNA transcripts were detected in only 1 (1.3%) case (positive predictive value of p16 staining for the presence of transcriptionally active HPV = 0.12). HPV mRNA transcripts were not detected in any patient under 40 (n = 11), or in patients who had never smoked (n=44), had quit smoking (n=15), and/or were only light consumers of alcohol (n = 57). Conclusions HPV is not detected in the vast majority of lateral tongue carcinomas. In light of the observation that HPV plays little if any role in the development of these cancers, routine HPV testing is unwarranted , even for patients without traditional risk factors. P16 staining is not a reliable marker for the presence of transcriptionally active HPV at this particular anatomic site. PMID:24485566

  20. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

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    Wolfgang Hagmann


    Full Text Available Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5 influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR, quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days did not alter the messenger RNA (mRNA expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1, whereas high dosages of the drug (20 µM for 1 hour elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine, the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1 or MRP5-silenced (PANC1/shMRP5 cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

  1. Human papillomavirus and post-transplant cutaneous squamous-cell carcinoma: a multicenter, prospective cohort study. (United States)

    Bouwes Bavinck, Jan Nico; Feltkamp, Mariet C W; Green, Adele C; Fiocco, Marta; Euvrard, Sylvie; Harwood, Catherine A; Proby, Charlotte M; Naldi, Luigi; Diphoorn, Janouk C D; Venturuzzo, Anna; Tessari, Gianpaolo; Nindl, Ingo; Sampogna, Francesca; Abeni, Damiano; Neale, Rachel E; Goeman, Jelle J; Quint, Koen D; Halk, Anne Berthe; Sneek, Carmen; Genders, Roel E; de Koning, Maurits N C; Quint, Wim G V; Wieland, Ulrike; Weissenborn, Sönke; Waterboer, Tim; Pawlita, Michael; Pfister, Herbert


    Organ-transplant recipients (OTR) have a 100-fold increased risk of cutaneous squamous-cell carcinoma (cSCC). We prospectively evaluated the association between beta-genus human-papillomaviruses (betaPV) and keratinocyte carcinoma in OTR. Two OTR cohorts without cSCC were assembled: cohort 1 transplanted in 2003-2006 (n=274) and cohort 2 in 1986-2002 (n=352). Participants were followed until death or cessation of follow-up in 2016. BetaPV infection was assessed in eyebrow hairs using PCR-based methods. BetaPV IgG seroresponses were determined by multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of betaPV using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HR). OTR with ≥5 different betaPV types in eyebrow hairs had 1.7 times the risk of cSCC versus those with 0-4 different types (HR: 1.7 (1.1;2.6)). A similar risk was seen with high betaPV loads (HR: 1.8 (1.2;2.8)). No significant associations were seen between serum antibodies and cSCC or between betaPV and basal-cell carcinoma. The diversity and load of betaPV types in eyebrow hairs are associated with cSCC risk in OTR, providing evidence that betaPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma. (United States)

    Larsson, Gabriella Lillsunde; Helenius, Gisela; Andersson, Sören; Sorbe, Bengt; Karlsson, Mats G


    The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis. Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing. 53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3.341; p=0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p=0.0002; p=0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate. HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase

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    Stefanou Nikolaos


    Full Text Available Abstract Background Numerous epidemiological studies have documented that obesity is associated with hepatocellular carcinoma (HCC. The aim of this study was to investigate the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and human telomerase reverse transcriptase (hTERT, a known mediator of cellular immortalization. Methods We investigated the relationship between leptin, leptin receptors and hTERT mRNA expression in HCC and healthy liver tissue samples. In HepG2 cells, chromatin immunoprecipitation assay was used to study signal transducer and activator of transcription-3 (STAT3 and myc/mad/max transcription factors downstream of leptin which could be responsible for hTERT regulation. Flow cytometry was used for evaluation of cell cycle modifications and MMP1, 9 and 13 expression after treatment of HepG2 cells with leptin. Blocking of leptin's expression was achieved using siRNA against leptin and transfection with liposomes. Results We showed, for the first time, that leptin's expression is highly correlated with hTERT expression levels in HCC liver tissues. We also demonstrated in HepG2 cells that leptin-induced up-regulation of hTERT and TA was mediated through binding of STAT3 and Myc/Max/Mad network proteins on hTERT promoter. We also found that leptin could affect hepatocellular carcinoma progression and invasion through its interaction with cytokines and matrix mettaloproteinases (MMPs in the tumorigenic microenvironment. Furthermore, we showed that histone modification contributes to leptin's gene regulation in HCC. Conclusions We propose that leptin is a key regulator of the malignant properties of hepatocellular carcinoma cells through modulation of hTERT, a critical player of oncogenesis.

  4. Multiple endocrine neoplasia similar to human subtype 2A in a dog: Medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma

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    E.A. Soler Arias


    Full Text Available Human multiple endocrine neoplasia subtype 2A (MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation.

  5. Complete acute gallbladder torsion diagnosed with abdominal ultrasonography and colour Doppler imaging. (United States)

    Ohkura, Yu; Hashimoto, Masaji; Sasaki, Kazunari; Watanabe, Goro


    An 82-year-old woman was admitted to our hospital with a provisional diagnosis of acute cholecystitis. Abdominal ultrasonography and colour Doppler imaging played the most important role in confirming a diagnosis of gallbladder torsion preoperatively, and we decided to treat it laparoscopically. Operative findings showed that gallbladder was rotated 360° counterclockwise around the cystic duct and artery. This was a complete torsion of a gross type I wandering gallbladder. The patient had an uneventful postoperative course and was discharged. Laparoscopic cholecystectomy has recently been recommended for treating gallbladder torsion. Because the gallbladder is typically minimally adherent to the liver bed, cholecystectomy can be performed easily with minimal invasion. Gallbladder torsion is a relatively rare cause of an acute abdomen and is difficult to diagnose preoperatively, but we could diagnose complete, acute gallbladder torsion preoperatively with ultrasonography and colour Doppler imaging in this case, allowing for safe and completely curative laparoscopic cholecystectomy.

  6. Cholescintigraphy in patients with acute cholecystitis before and after percutaneous gallbladder drainage

    DEFF Research Database (Denmark)

    Borly, L; Stage, J G; Grønvall, S


    OBJECTIVE: To investigate gallbladder function by use of cholescintigraphy in patients with acute cholecystitis before and after percutaneous gallbladder drainage. DESIGN: A cholescintigraphy was performed in 40 patients with acute cholecystitis before and after the performance of percutaneous...... gallbladder drainage. During the post-drainage cholescintigraphies, a cholecystokinin stimulation was performed to investigate gallbladder emptying in 12 selected patients. Gallbladder pressure and volume were measured before drainage in another group of 12 patients with acute cholecystitis. RESULTS...... treatment. Post-drainage cholescintigraphy revealed a mean gallbladder ejection fraction of 24%, which is significantly lower than the corresponding value in normal individuals and gallstone patients without cholecystitis (n = 12). Gallbladder pressure and volume were markedly increased compared with normal...

  7. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  8. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Dai W


    Full Text Available Wei Dai,1,2 Changfu Sun,1,2 Shaohui Huang,1,2 Qing Zhou1,21Department of Oromaxillofacial-Head and Neck Surgery, 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.Keywords: carvacrol, proliferation, metastasis and invasion, oral squamous cell carcinoma

  9. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper


    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  10. Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin. (United States)

    Poindessous, Virginie; Koeppel, Florence; Raymond, Eric; Comisso, Martine; Waters, Stephen J; Larsen, Annette K


    To characterize the activities of irofulven, a novelanticancer agent derived from the mushroom natural productilludin S toward human cancer cells. We have determined the activity spectrum of irofulven toward a human tumor cell panel comprised of 10 different tumor types in comparison with cisplatin and ET-743. We have also evaluated the influence of major resistance mechanisms, such as expression of multidrug resistance-associated drug efflux pumps, cisplatin resistance, loss of p53 function, and absence of mismatch repair on the cytotoxic activity of irofulven. The activity spectrum of irofulven is clearly different from that of ET-743 and cisplatin. Irofulven shows excellent cytotoxicity toward the majority of human carcinoma cell lines tested, but lesser activity toward sarcoma and leukemia cell lines. The cytotoxic activity of irofulven was particularly pronounced toward head and neck, non-small cell lung, colon, and ovary carcinoma cells, as well as toward malignant glioma cell lines. In addition, irofulven displayed good activity toward poorly differentiated, androgen-independent prostate cancer cells and cell lines expressing high levels of the detoxifying enzymes glutathione S-transferase and gamma-glutamyl cysteine synthetase. The cytotoxicity of irofulven was not affected by loss of p53 or mismatch repair function, and the drug was not a substrate for multidrug transporters, such as the P-glycoprotein and multidrug resistance protein 1. Irofulven has an unusual activity spectrum with strong activity toward tumor cells of epithelial origin. Furthermore, irofulven is not or only marginally affected by resistance mechanisms limiting the efficacy of other alkylating agents.

  11. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue

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    Basten Sander G


    Full Text Available Abstract Background Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney. Methods We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential. Results Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient

  12. Macrophages modulate migration and invasion of human tongue squamous cell carcinoma. (United States)

    Pirilä, Emma; Väyrynen, Otto; Sundquist, Elias; Päkkilä, Kaisa; Nyberg, Pia; Nurmenniemi, Sini; Pääkkönen, Virve; Pesonen, Paula; Dayan, Dan; Vered, Marilena; Uhlin-Hansen, Lars; Salo, Tuula


    Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF

  13. Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells. (United States)

    Cui, Xiaobo; Song, Laixiao; Bai, Yunfei; Wang, Yaping; Wang, Boqian; Wang, Wei


    Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival. © 2017 The Author(s).

  14. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. (United States)

    Repass, John; Maherali, Nimet; Owen, Kate


    The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from 'Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma' by Castellarin and colleagues published in Genome Research in 2012 (Castellarin et al., 2012). The experiment to be replicated is reported in Figure 2. Here, Castellarin and colleagues performed a metagenomic analysis of colorectal carcinoma (CRC) to identify potential associations between inflammatory microorganisms and gastrointestinal cancers. They conducted quantitative real-time PCR on genomic DNA isolated from tumor and matched normal biopsies from a patient cohort and found that the overall abundance of Fusobacterium was 415 times greater in CRC versus adjacent normal tissue. These results confirmed earlier studies and provide evidence for a link between tissue-associated bacteria and tumorigenesis. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

  15. Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous carcinoma cells

    Directory of Open Access Journals (Sweden)

    Thangavelu Lakshmi


    Full Text Available Oral cancer is in approximately 30% of all cancers in India. This study was conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia catechu bark (ACB against human squamous cell carcinoma cell line-25 (SCC-25. Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25 cells with 25 and 50 μg/mL for 24 h. Apoptosis markers such as caspases-8 and 9, bcl-2, bax, and cytochrome c (Cyt-c were done by RT-PCR. Morphological changes of ACB treated cells were evaluated using acridine orange/ethidium bromide (AO/EB dual staining. Nuclear morphology and DNA fragmentation were evaluated using propidium iodide (PI staining. Further, cell cycle analysis was performed using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells with an IC50 of 52.09 μg/mL. Apoptotic marker gene expressions were significantly increased on ACB treatment. Staining with AO/EB and PI shows membrane blebbing and nuclear membrane distortion, respectively, and it confirms the apoptosis induction in SCC-25 cells. These results suggest that ACB extract can be used as a modulating agent in oral squamous cell carcinoma.

  16. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway. (United States)

    Song, Bin; Shu, Ying; Cui, Tianlei; Fu, Ping


    Hypoxia-inducible factor 1-alpha (HIF-1α) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF-1α. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1α were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF-1α protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1α could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway.

  17. Acetaminophen Enhances Cisplatin- and Paclitaxel-mediated Cytotoxicity to SKOV3 Human Ovarian Carcinoma (United States)

    Wu, Y. Jeffrey; Neuwelt, Alexander J.; Muldoon, Leslie L.; Neuwelt, Edward A.


    Background Ovarian cancer is commonly treated with cisplatin/paclitaxel but many tumors become resistant. Acetaminophen reduced glutathione and enhanced chemotherapy efficacy in treating hepatic cancer. The objective of this study was to examine if acetaminophen enhances the cytotoxicity of cisplatin/paclitaxel in ovarian cancer. Materials and Methods SKOV3 human ovarian carcinoma cells in vitro and a subcutaneous tumor nude rat model were used and treated with cisplatin/paclitaxel with or without acetaminophen. Results In vitro, acetaminophen enhanced apoptosis induced by cisplatin and paclitaxel with similar effects on glutathione, reactive oxygen species and mitochondrial membrane potential but different effects on nuclear factor erythroid 2-related factor 2 (NRF2) translocation. In vivo, acetaminophen was uniformly distributed in tissue and significantly reduced hepatic glutathione. Acetaminophen enhanced cisplatin chemotherapeutic effect by reducing tumor recurrence Conclusion Our results suggest that acetaminophen as a chemoenhancing adjuvant could improve the efficacy of cisplatin and paclitaxel in treating patients with ovarian carcinoma and other tumor types. PMID:23749887

  18. Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Zorka Milićević


    Full Text Available In breast carcinoma, disruption of the p53 pathway is one of the most common genetic alterations. The observation that the p53 can express multiple protein isoforms adds a novel level of complexity to the outcome of p53 mutations. p53 expression was analysed by Western immunoblotting and immunohistochemistry using monoclonal antibodies DO-7, Pab240, and polyclonal antiserum CM-1. The more frequently p53-positive nuclear staining has been found in the invasive breast tumors. One of the most intriguing findings is that mutant p53 appears as discrete dot-shaped regions within the nucleus of breast cancer cells. In many malignant cells, the nucleolar sequestration of p53 is evident. These observations support the view that the nucleolus is involved directly in the mediation of p53 function or indirectly by the control of the localization of p53 interplayers. p53 expressed in the nuclear fraction of breast cancer cells revealed a wide spectrum of isoforms. p53 isoforms ΔNp53 (47 kDa and Δ133p53β (35 kDa, known as dominant-negative repressors of p53 function, were detected as the most predominant variants in nuclei of invasive breast carcinoma cells. The isoforms expressed also varied between individual tumors, indicating potential roles of these p53 variants in human breast cancer.

  19. Human papilloma virus in oral squamous cell carcinoma in a Mexican population. (United States)

    Ibieta, Blanca R; Lizano, Marcela; Fras-Mendivil, Mauricio; Barrera, José L; Carrillo, Adela; Ma Ruz-Godoy, Luz; Mohar, Alejandro


    To determine the human papilloma virus (HPV) infection in oral cancer and its association with smoking and drinking habits. A cross-sectional study was performed; samples were collected from 51 patients with histological diagnosis of squamous-cell carcinoma were collected at the Instituto Nacional de Cancerología in Mexico City. HPV infection was detected by polymerase chain reaction, and the clinical characteristics of this population were analyzed. Fifty samples out of 51 were positive for beta-globin; 21 (42%) cases were HPV-positive, and 14/21 were positive for HPV-16. We found more samples positive in men than in women (71% vs 29%). No differences were observed between HPV-positive and -negative patients in relation to smoking and drinking habits (81% vs 79%). HPV infection was present in 42% of patients with oral squamous-cell carcinoma (OSCC); HPV-16 was the most frequent type, identified in 66.6%. Other cofactors participate in the development of OSCC, independent of HPV infection.

  20. First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method. (United States)

    Nuccitelli, Richard; Wood, Ryan; Kreis, Mark; Athos, Brian; Huynh, Joanne; Lui, Kaying; Nuccitelli, Pamela; Epstein, Ervin H


    This nanoelectroablation therapy effectively treats subdermal murine allograft tumors, autochthonous basal cell carcinoma (BCC) tumors in Ptch1+/-K14-Cre-ER p53 fl/fl mice, and UV-induced melanomas in C57/BL6 HGF/SF mice. Here, we described the first human trial of this modality. We treated 10 BCCs on three subjects with 100-1000 electric pulses 100 ns in duration, 30 kV/cm in amplitude, applied at 2 pulses per second. Seven of the 10 treated lesions were completely free of basaloid cells when biopsied and two partially regressed. Two of the 7 exhibited seborrheic keratosis in the absence of basaloid cells. One of the 10 treated lesions recurred by week 10 and histologically had the appearance of a squamous cell carcinoma. No scars were visible at the healed sites of any of the successfully ablated lesions. One hundred pulses were sufficient for complete ablation of BCCs with a single, 1-min nanoelectroablation treatment. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line. (United States)

    Behnam Rassouli, F; Matin, M M; Iranshahi, M; Bahrami, A R; Neshati, V; Mollazadeh, S; Neshati, Z


    Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.

  2. Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment. (United States)

    Xu, Yangyang; Gu, Xin; Gong, Mancheng; Guo, Guiying; Han, Kaiyu; An, Ruihua


    The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.

  3. c-Fos is involved in inhibition of human bladder carcinoma T24 cells by brazilin. (United States)

    Zhang, Tingting; Fan, Xinping; Song, Lili; Ren, Lu; Ma, Enbo; Zhang, Shengwan; Ren, Liansheng; Zheng, Yaowu; Zhang, Jianzhen


    Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viability of T24 cells in a dose- and time-dependent manner, with a calculated LC50 of 32 µg/mL. More than 1,000 of genes were found upregulated and down regulated by brazilin treatment in digital gene expression profiling. Gene ontology analysis indicated that stress response, apoptosis, and cell cycle regulatory pathways were highly enriched. Among the regulated genes, c-Fos was the most and specifically upregulated. Overexpression of c-Fos in T24 cells resulted in tumor cell specific changes in cell morphology and viability. Over expression of stress-responsive gene, HSP70, and other highly upregulated genes did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and trigger cell death through a c-Fos-mediated and tumor cell specific signaling pathway. Further studies of its down stream mediators may help to identify better tumor cell type specific drug targets. © 2015 International Union of Biochemistry and Molecular Biology.

  4. Gene methylation of human ovarian carcinoma stromal progenitor cells promotes tumorigenesis. (United States)

    Ho, Chih-Ming; Shih, Daniel Tzu-Bi; Hsiao, Chih-Chiang; Huang, Shih-Hung; Chang, Shwu-Fen; Cheng, Wen-Fang


    This study aimed to investigate whether the DNA methylation of human ovarian carcinoma stromal progenitor cells (OCSPCs) could promote the tumorigenesis of ovarian carcinoma. OCSPCs were first isolated from fresh tumor tissues and ascites of ovarian cancer patients. In vivo and in vitro experiments on the effect of the OCSPCs on tumorigenesis and the effects of DNA demethylation on the OCSPCs were then performed. The OCSPCs possessed self-renewal and multipotent differentiation capacity with elevated expressions of OCT4, NANOG, BMP2, BMP4, Rex-1, AC133 and TGF-β. The OCSPCs, when combined with tumor cells in vivo could promote tumor growth. The methylation profiles of tumor suppressor genes (TSGs) were significantly higher in the OCSPCs than in ovarian cancer cells (p cells. The expression levels of TSGs were re-expressed by 5-aza-2-dC to inhibit the self-renewal and growth of OCSPCs. OCSPCs with decreased TSG expressions in the ovarian tumor microenvironment were able to promote tumorigenesis which could be reversed by DNA demethylation. DNA demethylation reversing the expression of TSGs in OCSPCs may represent a potential therapeutic target for ovarian cancer.

  5. Ultrasonographic differentiation of biliary atresia and neonatal hepatitis: Reestablishment of size criteria of the gallbladder

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    Kim, Woo Sun; Cheon, Jung Eun; Koh, Young Hwan; Kim, In One; Yeon, Kyung Mo [Seoul National University College of Medicine and Institude of Radiation Medicion, Seoul (Korea, Republic of)


    To reestablish the size criterion of the gallbladder on ultrasonography (US) for the differentiation diagnosis of biliary atresia from neonatal hepatitis. Abdominal US ws performed in 201 patients with jaundice and 40 patients without evidence of jaundice or hepatobiliary illness (all with the age less than 4 months). US was performed in fasting (fasting for at least 4 hours) to measure the length of the gallbladder and calculated the area of the gallbladder lumen. The morphology of the gallbladder was classified into three types: normal, elongated and atretic. To evaluate the contractibility of the gallbladder, the length of the gallbladder and area of the gallbladder lumen was again measured 1 hour after feeding. The final diagnosis included biliary atresia in 79 patients and neonatal hepatitis in 83 patients. Differences in the length, area, and morphology of the gallbladder were statistically significant among three groups, the normal group, neonatal hepatitis group and biliary atresia group (length and area of gallbladder; normal group>neonatal hepatitis>biliary atresia). The differences in the length and area of gallbladder between pre- and postmeal state were statistically significant in the normal and neonatal hepatitis groups whereas those of biliary atresia were not significant (p=0.85). When the empirical size criterion of the gallbladder (<15 mm in length) was applied, the sensitivity, specificity and diagnostic accuracy for the differential diagnosis of biliary atresia from hepatitis were 52%, 82%, and 67%, respectively. Meanwhile, if the area criterion(<30 mm{sup 2} in area) was applied, the sensitivity, the specificity and diagnostic accuracy were 67%, 85%, and 75%, respectively. Ultrasonographic evaluation of the morphology as well as size of the gallbladder are helpful in the differential diagnosis of biliary atresia from neonatal hepatitis. Therefore, since the measurement of the area of gallbladder lumen on US reflect both size and morphology of

  6. Gallbladder Polyps: An Ambiguous Cause of Biliary Colic

    African Journals Online (AJOL)

    detection rates of polyps have increased. On ultrasonography, they appear as fixed hyperechoic mass lesion projecting in the gallbladder lumen with or without an acoustic shadow.[3] Even though, the first‑line investigation of choice, ultrasonography is considered less sensitive in diagnosing polyps less than 1 cm diameter ...

  7. A porcelain gallbladder affecting the assessment of bone mineral content. (United States)

    Roland, J; Pouliart, C; Raeman, F; Williame, L; Vandevivere, J


    Dual-photon absorptiometry is a reliable method for the assessment of bone mineral content (BMC). The presence of focal bone disease, degenerative joint disease, or aortic calcifications may complicate the evaluation of BMC and may lead to erroneous findings. The misleading effect of a porcelain gallbladder is described.

  8. Non-operative Management of Gallbladder Perforation After Blunt ...

    African Journals Online (AJOL)

    to have a soft, distended abdomen, with localized upper peritonism. A repeat CT scan reported free fluid and a perforated gallbladder [Figure 1]. In view of his comorbidities, the patient was considered high risk for a general anesthetic and major abdominal surgery. After multidisciplinary discussion conservative.

  9. Acute gallbladder torsion - a continued pre-operative diagnostic dilemma

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    Desrochers Randal


    Full Text Available Abstract Acute gallbladder volvulus continues to remain a relatively uncommon process, manifesting itself usually during exploration for an acute surgical abdomen with a presumptive diagnosis of acute cholecystitis. The pathophysiology is that of mechanical organo-axial torsion along the gallbladder's longitudinal axis involving the cystic duct and cystic artery, and with a pre-requisite of local mesenteric redundancy. The demographic tendency is septua- and octo-genarians of the female sex, and its overall incidence is increasing, this being attributed to increasing life expectancy. We discuss two cases of elderly, fragile women presenting to the emergency department complaining of sudden onset right upper quadrant abdominal pain. Their subsequent evaluation suggested acute cholecystitis. Ultimately both were taken to the operating room where the correct diagnosis of gallbladder torsion was made. Pre-operative diagnosis continues to be a major challenge with only 4 cases reported in the literature diagnosed with pre-operative imaging; the remainder were found intra-operatively. Consequently, a delay in diagnosis can have devastating patient outcomes. Herein we propose a necessary high index of suspicion for gallbladder volvulus in the outlined patient demographic with symptoms and signs mimicking acute cholecystitis.

  10. Heterotopic gastric mucosa involving the gallbladder and biliary tree

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    Madrid, Carmen; Berrocal, Teresa; Gorospe, Luis; Prieto, Consuelo [Department of Paediatric Radiology, Hospital Infantil ' ' La Paz' ' , Paseo de la Castellana 261, 28046 Madrid (Spain); Gamez, Manuel [Department of Paediatric Surgery, Hospital Infantil ' ' La Paz' ' , Madrid (Spain)


    A case of heterotopic gastric mucosa in the common bile duct, cystic duct and gallbladder is reported in a 3-year-old girl with abdominal pain and jaundice. Abdominal US and CT showed dilatation of the biliary tree and a well-defined mass in the common bile duct that narrowed its lumen. The gallbladder was contracted in both examinations. The common bile duct and the gallbladder were resected and a choledochojejunostomy was performed. Although gastric heterotopy has been described throughout the entire length of the gastrointestinal tract, it is a very uncommon finding in the gallbladder and extremely rare in the biliary tree. A firm diagnosis of gastric heterotopia is based on the presence of fundal mucosa replete with parietal and chief cells. To our knowledge, this is the fifth reported case of heterotopic gastric tissue within the common bile duct, and the first to describe the US and CT findings. A relevant literature review and brief outline of the histological and radiological features are included in the discussion. (orig.)

  11. Gallbladder mucocele in a dog: an ultrasonography and pathology report


    THANGAPANDIYAN, Marudhai; SRIDHAR, Ramasamy; JEYARAJA, Kirubakaran; SAKTHIVELAN, Masilamani


    A 9-year old male, German shepherd dog was presented to the Madras Veterinary College Teaching Hospital with a history of a chronic ailment that had increased over the previous few months. A diagnosis of chronic renal failure and hepatitis was made and abdominal ultrasonography revealed the presence of gallbladder mucocele (GBM). The etiology, diagnosis, necropsy, and histopathological lesions were discussed.

  12. Non‑operative Management of Gallbladder Perforation After Blunt ...

    African Journals Online (AJOL)

    Isolated gallbladder perforations following blunt abdominal trauma are very rare. They often present with insidious onset of symptoms a few days after the initial insult and an operative course of management ensues. This is in the form of a cholecystectomy and peritoneal lavage; more often via laparotomy rather than ...

  13. Growth of human prostate carcinomas with and without hormone alpha- dehydrotestosterone in nude mice. (United States)

    Baisch, H; Otto, U; Fack, H


    The dependence of human prostate carcinoma growth on hormone was studied in xenotransplants in nude mice. The objective was to determine differences in cell kinetic parameters and volume growth of tumors growing with alpha-dehydrotestosterone (alphaDHT) and without alphaDHT. These differences could be used as arguments pro and contra the adaptation versus the clonal selection hypothesis. Human prostate carcinomas were xenotransplanted into nude mice. Growth of tumors was observed in castrated male mice without and with implanted osmotic pumps secreting alphaDHT. In a further series of experiments the alphaDHT tubes were removed when the tumors had reached a volume of 0.3 cm3. Tumor volume was measured to determine tumor doubling time with and without alphaDHT. Detailed cell kinetics were analyzed using the bromodeoxyuridine (BrdUrd) method with flow cytometry. Applying the relative movement (RM) and a simulation analysis to parallel single and multiple BrdUrd labelling experimental data we determined transit times through the phases of cell cycle, potential doubling time Tpot, growth fraction (GF) and cell loss. Five human prostate carcinomas were xenotransplanted into nude mice. Tumor take was only achieved when androgen hormone was present. However, when alphaDHT was removed when the tumors had grown to a volume of 0.3 cm3, they continued to grow at nearly the same Td as those tumors with continued alphaDHT application. The BrdUrd experiments, on the other hand, showed considerable increase of Tc and Tpot upon withdrawal of alphaDHT in 4 out of 5 tumors. The GF and labelling index (LI) were maintained at about the same level as alphaDHT consuming tumors. While small transplanted tumor pieces do not grow without alphaDHT, larger tumors grow with the same Td after removal of alphaDHT. The slower proliferation shown by the increased Tc and Tpot is balanced by less cell loss. Since GF and LI were maintained at about the same level, we conclude that in our tumors the

  14. Papilomavírus humano e sua associação com o carcinoma colorretal Human papillomavirus and its association with colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Carmen Ruth Manzione


    Full Text Available Atualmente, sabe-se que 15% dos tumores malignos humanos têm associação com infecções virais. Destes, 80% correspondem aos carcinomas da cérvix uterina, associados ao papilomavírus humano (HPV, e aos hepatocarcinomas. Nos últimos anos, entretanto, artigos da literatura especializada vêm mostrando a presença do DNA do HPV em amostras de tecido de carcinomas do esôfago, estômago, pulmão, da mama e do cólon e reto, o que foi negado por outros autores. O HPV vem sendo encontrado entre 41,7 e 82,1% dos adenocarcinomas e entre 28 e 56% dos adenomas do cólon. Embora o DNA viral esteja integrado ao tumoral, a maneira de contaminação não é evidente. As vias linfáticas e hematogênicas não são reconhecidas. Fica a dúvida quanto à especificidade dos exames de detecção viral e quanto às formas de disseminação viral para os segmentos mais proximais do cólon. De qualquer forma, a literatura não é categórica em afirmar se esse vírus pode ser agente causal da doença, sendo necessários mais estudos para definir esse assunto.Nowadays, we know that 15% of all malignancies have association with viral infections; 80% of them are cervical carcinomas, provoked by human papillomavirus (HPV, and liver carcinomas. However, in the last years, many articles are revealing HPV types occurrence in specimens of carcinomas from esophagus, stomach, lung, breast and colon and rectum, which was denied by other authors. HPV DNA was found in 41.7 to 82.1% of colon carcinomas and in 28 to 56% of colon adenomas. Although viral DNA is integrated with tumoral DNA, the way of contamination is not evident. Hematogenic and lymphatic routes are not well defined. There is doubt concerning the specificity of the exams of viral detection and the ways of viral dissemination in proximal colonic segments. Anyway, literature is not sure to affirm if this virus could be causal agent of this kind of cancer, and more studies are necessary.

  15. Decreased helenalin-induced cytotoxicity by flavonoids from Arnica as studied in a human lung carcinoma cell line

    NARCIS (Netherlands)

    Woerdenbag, HJ; Merfort, [No Value; Schmidt, TJ; Passreiter, CM; Willuhn, G; vanUden, W; Pras, N; Konings, AWT


    The effect of the flavones apigenin, luteolin, hispidulin and eupafolin, and of the flavonols kaempferol, quercetin, 6-methoxykaempferol and patuletin from Amica spp, on the cytotoxicity of the sesquiterpene lactone helenalin was studied in the human lung carcinoma cell line GLC(4) using the

  16. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues. (United States)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor


    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (ppolarimetry together with PLS statistics hold promise for automated pathology classification. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.


    Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

  18. Differentiation between gallbladder cancer with acute cholecystitis: Considerations for surgeons during emergency cholecystectomy, a cohort study. (United States)

    Kim, Sung Hoon; Jung, Dawn; Ahn, Jhii-Hyun; Kim, Kyung Sik


    Gallbladder cancer (GBCA) is an uncommon malignancy with vague and non-specific symptoms. GBCA is sometimes diagnosed after emergency cholecystectomy for acute cholecystitis. We investigated the differential diagnosis between GBCA with acute cholecystitis. Thirteen patients were diagnosed with GBCA after emergency cholecystectomy carried out for acute cholecystitis. A radiologist who was blinded to the final diagnoses retrospectively reviewed the computed tomography (CT) scans of the patients with GBCA and 25 patients with acute cholecystitis. We retrospectively reviewed the medical records of these patients and compared the clinical characteristics and CT findings between patients with GBCA and those with acute cholecystitis. We also investigated the prognostic factors in patients with GBCA who underwent emergency cholecystectomy. Gallbladder (GB) stones were found more often in patients with acute cholecystitis (n = 17, 68%) than in patients with GBCA (n = 7, 53.8%) (p = 0.486). Patients with GBCA showed typical GB masses or focal enhanced wall thickening when compared to diffuse wall thickening in patients with acute cholecystitis. Some GBCA patients showed irregular mural thickening and GB enhancement. Differentiating carcinoma from acute cholecystitis might sometimes not possible, but the latter group of patients had significantly lower C-reactive protein (CRP) levels (p = 0.033) and less regional fat stranding (p = 0.047). Survival was significantly affected by aggressive tumor characteristics (lymphatic invasion [p = 0.025], depth of tumor invasion [p = 0.004]) or R0 resection (p = 0.013) rather than bile spillage (p = 0.112). Surgeons deciding on emergency cholecystectomy for elderly patients with acute cholecystitis must suspect GBCA in patients with a low CRP level, irregular mural thickening or enhancement of GB without regional fat stranding. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Drug-induced gallbladder disease. Incidence, aetiology and management. (United States)

    Michielsen, P P; Fierens, H; Van Maercke, Y M


    A great variety of drugs is reported to induce gallbladder disease by various pathogenetic mechanisms. Early epidemiological studies indicated a doubled risk of gallbladder disease in women taking oral contraceptives. More recent studies, however, have failed to confirm those findings; these conflicting results might be explained by the different methods used to define gallbladder disease. It was shown that the lithogenic index of the bile is increased during intake of oral contraceptives. Estrogens cause hypersecretion of cholesterol in bile, due to increase in lipoprotein uptake by the hepatocyte. Progesterone inhibits acyl coenzyme A-cholesterol acyl transferase (ACAT) activity, causing delayed conversion of cholesterol to cholesterol esters. Of the lipid lowering drugs, only clofibrate has been shown to increase the risk for gallstone formation. The other fibric acid derivatives have similar properties, but clinical experience is not as extensive. They seem to be inhibitors of the ACAT enzyme system, thereby rendering bile more lithogenic. Conflicting epidemiological data exist regarding the induction of acute cholecystitis by thiazide diuretics. Ceftriaxone, a third-generation cephalosporin, is reported to induce biliary sludge in 25 to 45% of patients, an effect which is reversible after discontinuing the drug. The sludge is occasionally a clinical problem. It was clearly demonstrated that this sludge is caused by precipitation of the calcium salt of ceftriaxone excreted in the bile. Long term use of octreotide is complicated by gallstone formation in approximately 50% of patients after 1 year of therapy, due to gallbladder stasis. Hepatic artery infusion chemotherapy by implanted pump is shown to be associated with a very high risk of chemically induced cholecystitis. Prophylactic cholecystectomy at the time of pump implantation is therefore advocated. Some drugs, such as erythromcyin or ampicillin, are reported to cause hypersensitivity

  20. Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

    Directory of Open Access Journals (Sweden)

    Bee Thomas


    Full Text Available Abstract Background Testicular germ cell tumors (TGCTs are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Methods Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Results Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B, receptors (FZD5, FZD6, FZD10, secreted inhibitors (SFRP4, SFRP1, and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine. Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines

  1. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Scheffner, M.; Muenger, K.; Byrne, J.C.; Howley, P.M. (National Cancer Inst., Bethesda, MD (United States))


    Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.

  2. Cell death after high-LET irradiation in orthotopic human hepatocellular carcinoma in vivo. (United States)

    Altmeyer, Anaïs; Ignat, Mihaela; Denis, Jean-Marc; Messaddeq, Nadia; Gueulette, John; Mutter, Didier; Bischoff, Pierre


    Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and a major health problem since the choice of treatment is limited due to chemo- and radio-resistance. It was previously reported that high linear energy transfer (LET) radiation induced massive autophagic cell death in the human HCC SK-Hep1 cell line in vitro. This study analyzed the effects of high-LET radiation on the same HCC tumor model, orthotopically transplanted into nude mice. For this purpose, after surgical xenograft in the liver, animals were irradiated with fast neutrons and cell death occurring in the tumors was assessed with various techniques, including electron microscopy and probe-based confocal laser endomicroscopy. Results indicate that considerable autophagy and only limited apoptosis took place in the tumor xenografts after high-LET irradiation. These data confirm the previous in vitro results, suggesting that autophagy may act as a predominant mode of cell death in the efficacy of high-LET radiation.

  3. Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kuo-How Huang

    Full Text Available Celecoxib, a cyclooxygenase-2 (COX-2 inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA, bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.

  4. Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction. (United States)

    Vasanth, Karunamoorthy; Ilango, Kaliappan; MohanKumar, Ramasamy; Agrawal, Aruna; Dubey, Govind Prasad


    Silver nanomaterial plays a crucial role in the growing field of nanotechnology as there is an increasing commercial demand for silver nanoparticles (AgNPs) owing to their wide biological applications. The present investigation aims at developing anti-cancerous colloidal silver using Moringa olifera stem bark extract. Electron and atomic force microscopic images were taken to analyze the surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs were tested against human cervical carcinoma cells (HeLa) and cell morphology was further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The efficiency of green synthesized AgNPs was studied with the help of fluorescence activated cell sorting (FACS) and was shown to induce apoptosis through reactive oxygen species (ROS) generation in HeLa cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Association of pretreatment body mass index and survival in human papillomavirus positive oropharyngeal squamous cell carcinoma. (United States)

    Albergotti, William G; Davis, Kara S; Abberbock, Shira; Bauman, Julie E; Ohr, James; Clump, David A; Heron, Dwight E; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L


    Pretreatment body mass index (BMI) >25kg/m(2) is a positive prognostic factor in patients with head and neck cancer. Previous studies have not been adequately stratified by human papilloma virus (HPV) status or subsite. Our objective is to determine prognostic significance of pretreatment BMI on overall survival in HPV+ oropharyngeal squamous cell carcinoma (OPSCC). This is a retrospective review of patients with HPV+ OPSCC treated between 8/1/2006 and 8/31/2014. Patients were stratified by BMI status (>/25kg/m(2) had a longer overall survival (HR=0.49, P=0.01) as well as a longer disease-specific survival (HR=0.43, P=0.02). Overall survival remained significantly associated with high BMI on multivariate analysis (HR=0.54, P=0.04). Pre-treatment normal or underweight BMI status is associated with worse overall survival in HPV+ OPSCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray. (United States)

    Chung, Eun Jung; Sung, Young Kwan; Farooq, Mohammad; Kim, Younghee; Im, Sanguk; Tak, Won Young; Hwang, Yoon Jin; Kim, Yang Il; Han, Hyung Soo; Kim, Jung-Chul; Kim, Moon Kyu


    We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.

  7. Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

    DEFF Research Database (Denmark)

    Engelholm, S A; Vindeløv, L L; Spang-Thomsen, M


    Specimens from a human small cell carcinoma of the lung were established as a cell line in vitro. Flow cytometric DNA analysis demonstrated only one tumor cell population in the parent tumor as well as in the early passages in vitro. After six passages in vitro, two new subpopulations...... content was examined regularly by flow cytometric DNA analysis and instability was found in one of the cloned cell lines. Chromosome analysis showed that the cloned cell lines consisted of more than one population after 17 in vitro passages. Both cloned cell lines produced tumors in nude mice. Genetic...... with different DNA content appeared. By cloning, permanent cell lines were established from the new subpopulations, whereas the original population stopped growing. The cloned cell lines were characterized by morphology, chromosomes analysis, electron microscopy and plating efficiency; the stability of the DNA...

  8. Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

    DEFF Research Database (Denmark)

    Wright, A; Andrews, N; Bardsley, K


    The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state...... of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment....... and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range...

  9. Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

    Directory of Open Access Journals (Sweden)

    Richard L. Cantley


    Full Text Available Squamous cell carcinoma (SCC of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

  10. Co-infection of syphilis and hepatitis B with carcinoma penis in a human immunodeficiency virus male. (United States)

    Govindan, Balaji; Subramanian, Kalaivani; Karunakaran, Maduravasagam


    Human immunodeficiency virus (HIV) infections have a high probability of co-infections with Syphilis and hepatitis B virus since they share the common routes of transmission. We report a 41-year-old HIV male (on antiretroviral therapy for the past 6 years) admitted for a complaint of penile ulcer for 2 months. Serology for syphilis and hepatitis B were positive. Skin biopsy of the penile ulcer confirmed squamous cell carcinoma. Henceforth, the patient was referred to oncology department for further management. We present this rare combination of syphilis and hepatitis B with carcinoma penis in an HIV patient.

  11. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Mincione, Gabriella, E-mail: [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Tarantelli, Chiara [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Vianale, Giovina [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Di Marcantonio, Maria Carmela [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cotellese, Roberto [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Francomano, Franco [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Di Nicola, Marta; Costantini, Erica [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cichella, Annadomenica [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Muraro, Raffaella [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy)


    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.

  12. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas. (United States)

    Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella


    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. [The molecular mechanisms of curcuma wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells in vitro]. (United States)

    Jing, Zhao; Zou, Hai-Zhou; Xu, Fang


    To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells. The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence. 100 microL RMPI-1640 culture medium containing 0.1% DMSO was added in Group 1 as the control group. 100 microL 25, 50, and 100 mg/L Curcuma Wenyujin extract complete culture medium was respectively added in the rest 3 groups as the low, middle, and high dose Curcuma Wenyujin extract groups. The effects of different doses of Curcuma Wenyujin extract (25, 50, and 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro were analyzed by MTT assay. The gene expression profile was identified by cDNA microarrays in esophageal carcinoma TE-1 cells exposed to Curcuma Wenyujin extract for 48 h. The differential expression genes were further analyzed by Gene Ontology function analysis. Compared with the control group, MTT results showed that Curcuma Wenyujin extract significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (PCurcuma Wenyujin extract could inhibit the growth of human esophageal carcinoma cell line TE-1 in vitro. The molecular mechanisms might be associated with regulating genes expressions at multi-levels.

  14. Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse. (United States)

    Kerjaschki, Dontscho; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Sexl, Veronika; Schneckenleithner, Christine; Wolbank, Susanne; Bartel, Gregor; Krieger, Sigurd; Kalt, Romana; Hantusch, Brigitte; Keller, Thomas; Nagy-Bojarszky, Katalin; Huttary, Nicole; Raab, Ingrid; Lackner, Karin; Krautgasser, Katharina; Schachner, Helga; Kaserer, Klaus; Rezar, Sandra; Madlener, Sybille; Vonach, Caroline; Davidovits, Agnes; Nosaka, Hitonari; Hämmerle, Monika; Viola, Katharina; Dolznig, Helmut; Schreiber, Martin; Nader, Alexander; Mikulits, Wolfgang; Gnant, Michael; Hirakawa, Satoshi; Detmar, Michael; Alitalo, Kari; Nijman, Sebastian; Offner, Felix; Maier, Thorsten J; Steinhilber, Dieter; Krupitza, Georg


    In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas.

  15. Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells. (United States)

    Rehman, Khurram; Mohd Amin, Mohd Cairul Iqbal; Yuen, Ng Pei; Zulfakar, Mohd Hanif


    Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.

  16. High-risk human papilloma virus genotypes in cervical carcinoma of Serbian women: Distribution and association with pathohistological findings. (United States)

    Stamenković, Miodrag; Knežević, Aleksandra; Knežević, Ivana; Kuzmanović, Igor; Karalić, Danijela; Milenković, Sanja; Jovanović, Tanja


    A significant role of high-risk Human papilloma viruses (HR HPV) in the development of cervical carcinoma is well known. HR HPV 16 and 18 account for approximately 70% of all cases of cervical cancer worldwide. The incidence of cervical cancer in Serbia, is one of the highest in Europe. The aim of our study was to investigate the distribution of HR HPV types in cervical carcinoma of Serbian women, as well as association between the HPV types and pathohistological findings. The study included 80 archival cervical cancer tissues from the same number of patients. The presence of HPV DNA was determined using MY09/MY11 primers for L1 gene and GP1/GP2 primers for E1 gene. HPV was detected in 78.75% tissues. HR HPV genotypes found in the decreasing order of frequency were: HPV16 (80.39%), HPV33 (7.84%), HPV58 (5.88%), HPV18 (1.96%), HPV45 (1.96%) and HPV53 (1.96%). The examined tissues were 91.25% squamous cell carcinomas and 8.75% adenocarcinoma. The high frequency of HPV 16 was observed in both types of carcinoma (80.8% and 75%, respectively) while the prevalence of HPV18 was low. These results may contribute to the implementation of cervical carcinoma prevention program in Serbia, including the selection of the most appropriate vaccine and immunization program. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  17. Evaluation of immunohistochemical expression of p16 and presence of human papillomavirus in oral and oropharyngeal carcinoma. (United States)

    Cantarutti, Ana Luíza Laguardia; Fernandes, Lais Papini; Saldanha, Marina Vaz de Lima Fullin; Marques, Ana Elizia Mascarenhas; Vianna, Leonora Maciel de Souza; de Melo, Nilce Santos; Guerra, Eliete Neves da Silva


    Carcinogenesis concerns several changes that eventually result in the inactivation of tumor suppressor genes and activation of protooncogenes, leading to loss of cell cycle control. Inactivation of p16 seems to be an early event in this process and occurs in approximately 80% of squamous cell carcinoma cases. The aims of this study were to evaluate the immunohistochemical expression of p16 protein in oral and oropharyngeal squamous cell carcinoma cases, with both the tumoral area itself and its surgical margin being analyzed (dysplastic areas and histologically normal epithelium adjacent to carcinoma), and to verify the presence of human papillomavirus (HPV) and its relation to p16 expression. Paraffin-embedded biopsy tissues from 26 patients, 13 with oral squamous cell carcinoma and 13 with oropharyngeal squamous cell carcinoma, comprised the analyzed samples. To detect HPV, a nested polymerase chain reaction test using PGMY 09/11 and GP5*/GP6* primers and visualization of the product on a 2% agarose gel was performed. Demographic data were obtained from medical records. The results showed low expression of p16 in the tumor area (38.46%), compared with surgical margins in the histologically normal epithelium (84.6%) and dysplastic areas (57.7%). These findings indicate the inactivation of p16 in the process of malignant transformation. The association described in the literature between expression of p16 and presence of HPV could not be verified in this study, because none of the cases was HPV positive.

  18. Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina

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    Kahn Tomas


    Full Text Available Abstract Background Infections with high-risk human papillomaviruses (HPVs, causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype. Methods HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I. Fischer's test with Woolf's approximation was used for statistical analysis. Results HPV DNA was detected in 17 out of 41 (41.5 % carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas. Conclusion These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas.

  19. Detection of human papilloma virus (HPV and human immunodeficiency virus (HIV in oral squamous cell carcinoma: A polymerized chain reaction (PCR study

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    Suresh Dirasantchu


    Full Text Available Aims and Objectives: Certain strains of human papillomavirus (HPV have been shown to be etiologically related to the development of uterine, cervical, and other genital cancers, but their role in the development of malignancies at other sites is less well established. Previous studies have shown HPV in tumors of the head and neck, but its prevalence has varied depending on the detection methods and the types of tumor and/or tissue examined. This study was undertaken for the detection of high-risk HPV types 16 and 18 and human immunodeficiency virus (HIV in oral squamous cell carcinoma. Materials and Methods: Twenty-five patients histologically diagnosed with oral squamous cell carcinoma and 10 apparently normal persons as controls were selected for the present study. Two biopsy specimens were removed surgically by incision biopsy for histopathological examination and polymerized chain reaction (PCR study. Results: Out of 25 oral squamous cell carcinoma subjects, 8 were found to be HPV positive in PCR. Out of these eight subjects, four had HPV 16 and the other four had other genotypes, and one subject was HIV positive. Conclusion: The conclusion drawn from the present study was that well-defined risk factors like HPV may play a prominent role in the development of oral squamous cell carcinomas, in addition to other risk factors. Further studies with a larger sample size are necessary to arrive at conclusions and to explore the relationship of HPV and HIV in oral squamous cell carcinoma.

  20. Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

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    G. Perrone


    Full Text Available The human equilibrative nucleoside transporter 1 (hENT1 is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively. Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036, while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

  1. Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study. (United States)

    Faouzi, S; Le Bail, B; Neaud, V; Boussarie, L; Saric, J; Bioulac-Sage, P; Balabaud, C; Rosenbaum, J


    Marked changes in extracellular matrix occur in the stroma of hepatocellular carcinoma, as compared to normal or cirrhotic liver. The cell types responsible for extracellular matrix synthesis within hepatocellular carcinoma have not been clearly identified. In vivo collagen synthesis was studied by in situ hybridization and immunohistochemistry for types I, IV, V and VI collagen, together with immunolabeling of alpha-smooth muscle actin, a myofibroblast marker, and CD34, an endothelial cell marker. In vitro, extracellular matrix deposition by cultured myofibroblasts was studied by reticulin staining, immunocytochemistry and RNase protection. All collagens studied were expressed in the stroma of the tumor, with a higher level of type VI and IV collagens than of type I and V. The majority of the cells expressing collagen transcripts in human hepatocellular carcinoma stroma were alpha-actin positive and CD 34 negative. In vitro experiments demonstrated that the hepatocellular carcinoma cell lines HepG2, HuH7 and Hep3B markedly increased extracellular matrix deposition by human liver myofibroblasts. This increase was mediated by a soluble mediator present in tumor cell conditioned medium. It was not explained by an increase in mRNA levels of extracellular matrix components, nor by a decrease in the secretion of matrix-degrading proteinases by myofibroblasts. Myofibroblasts are the main source of collagens in the stroma of hepatocellular carcinoma. Our data also indicate that tumoral hepatocytes increase extracellular matrix deposition by cultured myofibroblasts, probably by post-transcriptional mechanisms. The generation of hepatocellular carcinoma stroma by myofibroblasts could thus be under control of tumoral cells.

  2. Estrogen mediated expression of nucleophosmin 1 in human endometrial carcinoma clinical stages through estrogen receptor-α signaling. (United States)

    Zhou, Yunxiao; Shen, Jie; Xia, Liqun; Wang, Yanli


    Endometrial carcinoma is one of the most common gynecologic malignancies. Estrogen plays a critical role in its pathogenesis, but the underlying mechanism is not clear. Nucleophosmin 1 (NPM1), a multifunctional protein involved in many cellular activities, has been implicated in the tumorigenesis processes. However, the role of NPM1 in endometrial carcinogenesis remains to be elucidated. The present study was aimed to elucidate the role of NPM1 in different clinical stages of human endometrial carcinoma and the underlying mechanism of NPM1 action. The distribution and expression of NPM1 in normal endometrium, FIGO stages I to IV endometrial carcinoma tissues was analyzed using immunohistochemistry, RT-qPCR and Western blotting. The association between NPM1 expression and estrogen and estrogen receptor signaling was investigated in primary-cultured FIGO stage I endometrial adenocarcinoma cells. A strong positive correlation between NPM1 level and the clinical stage and histological grade of endometrial carcinomas was observed. Expression of NPM1 was up-regulated by estrogen in primary-cultured human endometrial adenocarcinoma cells. Furthermore, estrogen increased NPM1 level via estrogen receptor-α (ERα) signaling, nor estrogen receptor-β signaling. Expression of NPM1 was gradually increased with the increase of clinical stages of endometrial carcinomas. Overexpression of NPM1 may play a role in the effects of estrogen on the malignant progression of endometrioid adenocarcinoma via ERα signaling. These findings may extend our understanding of the oncogenesis of steroid hormone-related cancers and have significance for the diagnosis and treatment of this carcinoma.

  3. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. (United States)

    Rao, Quan; Zuo, Bingfeng; Lu, Zhen; Gao, Xianjun; You, Abin; Wu, Chenxuan; Du, Zhi; Yin, HaiFang


    Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472). © 2016 by the American Association for the Study of Liver Diseases.

  4. Integrative Genomic Analysis Identifies the Core Transcriptional Hallmarks of Human Hepatocellular Carcinoma. (United States)

    Allain, Coralie; Angenard, Gaëlle; Clément, Bruno; Coulouarn, Cédric


    Integrative genomics helped characterize molecular heterogeneity in hepatocellular carcinoma (HCC), leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here, we performed a meta-analysis of 15 independent datasets (n = 784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared with the surrounding nontumor tissue. In the HCC signature, upregulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer. Cancer Res; 76(21); 6374-81. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

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    Ioannis Anestopoulos


    Full Text Available Silibinin, extracted from milk thistle (Silybum marianum L., has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2 members Enhancer of Zeste Homolog 2 (EZH2, Suppressor of Zeste Homolog 12 (SUZ12, and Embryonic Ectoderm Development (EED in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR. Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ-27 residue (H3K27me3 levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473 (pAkt and phosphorylated EZH2 (ser21 (pEZH2. Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT activity while it decreased histone deacetylases 1-2 (HDACs1-2 expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.

  6. Listeria monocytogenes mutants defective in gallbladder replication represent safety-enhanced vaccine delivery platforms. (United States)

    Dowd, Georgina C; Bahey-El-Din, Mohammed; Casey, Pat G; Joyce, Susan A; Hill, Colin; Gahan, Cormac G M


    The Gram positive intracellular pathogen Listeria monocytogenes represents a promising vaccine or therapeutic DNA delivery vector that has been successfully administered to humans in clinical trials. However in generating Listeria mutants with therapeutic potential it is important to balance safety attenuation with efficacy. Here we show that L. monocytogenes mutants with a reduced capacity for murine gallbladder replication are capable of stimulating T cell responses in mice and protecting vaccinated animals from secondary challenge. Mutation of L. monocytogenes genes lmo2566 or lmo0598 resulted in significant attenuation in the murine model yet mutants retained a capacity for intracellular growth and stimulation of T cell responses against key Listeria epitopes (LLO91-99 and P60217-225). Importantly the mutants showed a reduced capacity for growth in the gallbladders of vaccinated mice as well as significantly reduced faecal shedding indicating that this approach generates live Listeria-based vector delivery systems with a reduced capacity for the spread of live genetically modified microorganisms into the natural environment.

  7. A practical guide for the identification of membrane and plasma membrane proteins in human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Mummery, C.L.; Krijgsveld, J.; Heck, A.


    The identification of (plasma) membrane proteins in cells can provide valuable insights into the regulation of their biological processes. Pluripotent cells such as human embryonic stem cells and embryonal carcinoma cells are capable of unlimited self-renewal and share many of the biological

  8. Detection of integrated human papillomavirus by human papillomavirus types 16 and 18 in situ hybridization: a valuable diagnostic tool in diagnosing cervical carcinoma?

    NARCIS (Netherlands)

    Golde, R.J.T. van; Hullu, J.A. de; Bekkers, R.L.M.; Bulten, J.; Grefte, J.M.


    Human papillomavirus (HPV) infection is an important factor in cervical carcinogenesis. We describe 3 cases of patients with difficulties in diagnosing either a primary or recurrent cervical carcinoma. These cases illustrate that detection of integrated HPV is helpful in diagnosing cervical

  9. Measurement of Gallbladder Volume with Ultrasonography in Pregnant Women

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    Sait Kapicioglu


    Full Text Available Fasting and postprandial gallbladder volumes were investigated using ultrasonography in three groups (10 subjects in each of healthy women: third trimester pregnant women, postpartum women up to 10 days after giving birth and nonpregnant controls. The scans were performed at 09:00 after a 12 h fast. After the basal measurement was taken, gallbladder volumes were rescanned in 15 min intervals for 60 mins. At the end of this period, all volunteers received a standard liquid test meal, and scans were performed again for 1 h. The mean basal gallbladder volume was 22.2±4.2 mL in the nonpregnant (control group. In the third trimester group, the basal volume was 37.8±10.5 mL – 70.5% higher than in the nonpregnant group (P<0.001. In the postpartum group, the mean basal volume was 37.9% lower (27.4±6.5 mL than that of the third trimester group (P<0.02. This basal volume was 23.6% greater than that of the control group (P<0.05. After administration of a test meal, the postprandial gallbladder volumes decreased during the first few minutes compared with baseline values. The volumes decreased by 10.2% to 39.8% (23.5±7.3 to 34.0±10.2; P<0.01 in the third trimester group, by 14.9% to 43.2% (16.6±4.3 to 23.3±5.5; P<0.01, 0.001 in the postpartum group and by 19.2% to 51.6% (11.9±3.5 to 17.9±3.6; P<0.02, 0.05, 0.01, 0.001 in the control group. Postprandial mean gallbladder volumes of the third trimester (P<0.02 and postpartum groups (P<0.02 to 0.01 were significantly different from those of the control group. In conclusion, incomplete emptying of the gallbladder after eating during the third trimester of pregnancy may contribute to cholesterol-gallstone formation, and pregnancy may thus increase the risk of gallstones.

  10. [Therapeutic effect of flavopiridol, a small molecular cyclin-dependent kinase inhibitor, in human ovarian carcinoma]. (United States)

    Song, Yue; Shen, Keng; Tang, Ping-ping


    To investigate the antitumor effect of flavopiridol in ovarian cancer. After the treatment with flavopiridol of AO cells, cell apoptotic rate and cell cycle distribution were detected by flow cytometer and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Real time PCR was used to detect the expression of cyclin D and active caspase-3 in AO cells. Subcutaneous tumor models and abdominally spread tumor models of human ovarian carcinoma using AO cells in BALB/c nude mice were established. The mouse survival rates were measured for abdominally spread tumor models and the volume of tumor nodules was determined for subcutaneous tumor models following the treatments of flavopiridol. TUNEL was used to detect cell apoptosis, and immunohistochemistry was used to measure microvessel density (MVD) in tumor tissues. AO cells showed apoptotic rates of 4.1%, 10.7% and 7.6% following the treatments with flavopiridol at 150, 300 and 500 nmol/L respectively, accompanied by an increase in G(1) progression and a decrease in S phase progression. The level of active caspase-3 increased (2.55 vs 2.49) and the level of cyclin D expression decreased significantly (0.25 vs 0.69, P flavopiridol. Flavopiridol prolonged mouse survival [mean survival time of (141 +/- 14) days] and suppressed tumor growth significantly (tumor growth suppression rate of 40%), when compared with treatment using phosphate-buffered saline [(106 +/- 11) days, P flavopiridol. MVD of tumor tissue was 12 +/- 5 following flavopiridol treatment, significantly higher than that of 35 +/- 10 treated with phosphate-buffered saline (P Flavopiridol results in significant suppression of ovarian carcinoma cell growth and prolongs survival of mice.

  11. Epithelial cell adhesion molecule in human hepatocellular carcinoma cell lines: a target of chemoresistence. (United States)

    Li, Yan; Farmer, Russell W; Yang, Yingbin; Martin, Robert C G


    The low survival rate of hepatocellular carcinoma (HCC) is partly attributable to its resistance to existing chemotherapeutic agents. Until now, there have been limited chemotherapeutic agents for liver cancer. Epithelial cell adhesion molecule (EpCAM) has been found to be over-expressed during stages of carcinogenesis and has been associated with poor overall survival in many cancers. The aim of this study was to evaluate EpCAM expression in HCC and evaluate the effects of EpCAM to established chemotherapy. Three human hepatocellular carcinoma cell lines--HepG2, Hep3B and HuH-7--were pre- and post-treated with doxorubicin, 5-fluorouracil (5-FU) and cisplatin. Cell viability and EpCAM protein expression were measured by MTT assay and Western Blotting respectively. EpCAM positive cells were analyzed by flow cytometry. To evaluate the effects of doxorubicin efficacy on EpCAM positive cells, a small interfering RNA (siRNA) specific to EpCAM was transfected into the cells and treated with doxorubicin. EpCAM was significantly down-regulated by doxorubicin treatment in all three HCC cell lines (P cells, however the EpCAM expression was up-regulated by 5-FU and cisplatin in Hep3B cell line. EpCAM expression was down-regulated by 5-FU, and up-regulated by cisplatin in Huh-7 cell line. Flow cytometry assay showed doxorubicin exposure decreased EpCAM positive cell quantities in three HCC cell lines. EpCAM siRNA knock-down attenuated cell mortality after doxorubicin exposure. All of these findings demonstrate that EpCAM is one of targets of chemoresistence.

  12. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues. (United States)

    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji


    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (povarian cancer and RCC tissue samples (povarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  13. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

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    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  14. Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients. (United States)

    Kouketsu, Atsumu; Sato, Ikuro; Abe, Satoko; Oikawa, Mariko; Shimizu, Yoshinaka; Takahashi, Tetsu; Kumamoto, Hiroyuki


    Recent evidence suggests that human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a separate HNSCC subgroup with distinct epidemiology, histopathological characteristics, therapeutic response to chemotherapy and radiation, and clinical outcome. This study aimed to investigate the role of HPV infection in oral squamous cell carcinoma (OSCC) and the correlation between HPV infection, tumor suppressor protein p16 expression, and clinicopathological features in Japanese patients. In total, 174 OSCC specimens were examined for p16 levels by immunohistochemistry, and p16-positive OSCCs were analyzed for HPV DNA by in situ hybridization (ISH) and HPV genotypes by real-time PCR. The results were evaluated for the association with clinicopathological characteristics of OSCC patients. Twenty-four OSCC samples were found positive for p16 expression; all of them were well-differentiated tumors. P16 immunoreactivity was significantly associated with the invasion depth and tended to correlate with sex, site in the oral cavity, stromal reaction, TNM stage, and survival. HPV DNA was detected in 13 of 24 (54%) p16-positive OSCC by real-time PCR; HPV 16, 18, and other high-risk genotypes were the most prevalent. However, ISH failed to detect HPV DNA in p16-positive OSCCs. P16 immunoreactivity and HPV genotyping by real-time PCR may be useful markers of HPV infection in OSCC. However, although HPV-related OSCC showed good outcomes, HPV infection may have a minor role in oral oncogenesis in Japanese patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Transcriptionally-active human papillomavirus is consistently retained in the distant metastases of primary oropharyngeal carcinomas. (United States)

    Mehrad, Mitra; Zhao, Hongwei; Gao, Ge; Wang, Xiaowei; Lewis, James S


    High-risk human papillomavirus (HPV) is both causative and prognostic in the majority of oropharyngeal squamous cell carcinomas (OPSCCs). The aim of this study was to evaluate for transcriptionally-active HPV in matched primary OPSCCs and their distant metastases given the implications of HPV status for diagnosis and treatment. Twenty matched pairs of primary OPSCC and their distant metastases were retrieved from departmental files. Two study pathologists reviewed all cases to confirm the diagnoses and to evaluate histologic features. Real-time PCR (RT-PCR) for detection of E6/E7 mRNA for all major high-risk HPV types and p16 immunohistochemistry were performed. Distant metastases were to lung (70 %), bone (20 %), non-regional lymph nodes (5 %) and pericardium (5 %). Histologically, 15 primary tumors were nonkeratinizing, 3 nonkeratinizing with maturation, one basaloid, and one keratinizing. Seventeen (85 %) of the metastases had the same histologic type as the primary tumor. All 20 matched pairs were concordant for HPV status by RT-PCR and for p16 expression with 19 of 20 cases positive for high risk HPV and one negative. HPV types were concordant in all cases. These findings show that the distant metastases from HPV-related primary OPSCCs uniformly retain transcriptionally-active HPV and p16 overexpression. They also retain similar morphology. This argues that HPV status can be utilized to differentiate metastatic OPSCC from separate, new, primary squamous cell carcinomas in other organs, and that therapies specifically targeting HPV or virus-related proteins in patients with distant metastases can be utilized.

  16. Cacospongionolide and scalaradial, two marine sesterterpenoids as potent apoptosis-inducing factors in human carcinoma cell lines. (United States)

    De Stefano, Daniela; Tommonaro, Giuseppina; Malik, Shoaib Ahmad; Iodice, Carmine; De Rosa, Salvatore; Maiuri, Maria Chiara; Carnuccio, Rosa


    Apoptosis, a form of programmed cell death, is a critical defence mechanism against the formation and progression of cancer and acts by eliminating potentially deleterious cells without causing such adverse effects, as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death. In the present study, we investigated the effects of scalaradial and cacospongionolide, two sesterterpenoids from Cacospongia scalaris and Fasciospongia cavernosa marine sponges, on the apoptotic signalling pathway in three different human tumoral cells. Results were obtained by using DNA fragmentation, comet and viability assays, quantification of the mitochondrial transmembrane potential and Western blot. The T47D (human breast carcinoma), A431 (human epidermoid carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial or cacospongionolide. Treatment of T47D cells with scalaradial or cacospongionolide for 24 h brought about a significant increase in DNA migration as well as fragmentation. Moreover, incubation of HCT116 and HeLa cells with scalaradial or cacospongionolide for 24 h caused an increased expression of pro-apoptotic proteins. Furthermore, scalaradial or cacospongionolide, added to HCT116 and HeLa cells overnight, induced a significant and concentration-dependent loss of mitochondrial transmembrane potential, an early apoptosis signalling event. These effects paralleled with those achieved with p50 and p65, NF-κB subunits, nuclear level. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell

  17. Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers. (United States)

    Aggarwal, Anshu; Hunter, William J; Aggarwal, Himanshu; Silva, Edibaldo D; Davey, Mary S; Murphy, Richard F; Agrawal, Devendra K


    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Inhibitory effect of iron withdrawal by chelation on the growth of human and murine mammary carcinoma and fibrosarcoma cells. (United States)

    Power Coombs, Melanie R; Grant, Taryn; Greenshields, Anna L; Arsenault, Daniel J; Holbein, Bruce E; Hoskin, David W


    Since iron uptake is essential for cell growth, rapidly dividing cancer cells are sensitive to iron depletion. To explore the effect of iron withdrawal on cancer cell growth, mouse and human mammary carcinoma cells (4T1 and MDA-MB-468, respectively) and mouse and human fibrosarcoma cells (L929 and HT1080, respectively) were cultured in the absence or presence of DIBI, a novel iron-chelating polymer containing hydroxypyridinone iron-ligand functionality. Cell growth was measured by a colorimetric assay for cell metabolic activity. DIBI-treated 4T1, MDA-MB-468, L929 and HT1080 cells, as well as their normal counterparts, showed a dose- and time-dependent reduction in growth that was selective for human cancer cells and mouse fibrosarcoma cells. The inhibitory effect of DIBI on fibrosarcoma and mammary carcinoma cell growth was reversed by addition of exogenous iron in the form of iron (III) citrate, confirming the iron selectivity of DIBI and that its inhibitory activity was iron-related. Fibrosarcoma and mammary carcinoma cell growth inhibition by DIBI was associated with S-phase cell cycle arrest and low to moderate levels of cell death by apoptosis. Consistent with apoptosis induction following DIBI-mediated iron withdrawal, fibrosarcoma and mammary carcinoma cells exhibited mitochondrial membrane permeabilization. A comparison of DIBI to other iron chelators showed that DIBI was superior to deferiprone and similar to or better than deferoxamine for inhibition of fibrosarcoma and mammary carcinoma cell growth. These findings suggest that iron withdrawal from the tumor microenvironment with a selective and potent iron chelator such as DIBI may prevent or inhibit tumor progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Analysis of gene expression changes associated with human carcinoma-associated fibroblasts in non-small cell lung carcinoma. (United States)

    Wu, Xiaofen; Ruan, Lei; Yang, Yi; Mei, Qi


    This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC). We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis. We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-β signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%. Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.

  20. Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma. (United States)

    Basic-Jukic, Nikolina; Hudolin, Tvrtko; Radic-Antolic, Margareta; Coric, Marijana; Zadro, Renata; Kastelan, Zeljko; Pasini, Josip; Bandic-Pavlovic, Daniela; Kes, Petar


    Recent studies demonstrated that the expression pattern of bone morphogenetic protein-7 (BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC). Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression was analyzed by immunohistochemistry. RT-PCR showed strong down-regulation of BMP-7 mRNA in cancer tissue. Immunohistochemistry revealed expression of BMP-7 in normal renal tissue, with almost complete loss of BMP-7 expression in malignant cells of 6 patients (30%). After 3 years of follow-up, 5 out of 6 patients with high BMP-7 mRNA expression were alive and disease-free, compared with 9 out of 14 patients with low BMP-7 mRNA expression. BMP-7 mRNA and protein expression were down-regulated in CCRC. Further prospective studies are needed to characterize the role of BMP-7 in human CCRC.

  1. Effects of guggulsterone on proliferation and apoptosis of HepG2 human hepatocellular carcinoma cells

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    JIA Xiaoli


    Full Text Available ObjectiveTo investigate the potential therapeutic effects of the plant-derived polyphenol, guggulsterone, on cell proliferation and apoptosis of hepatocellular carcinoma (HCC by using an in vitro system with the human hepatoma cell line, HepG2. MethodsHepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L for 24-72 hours. Differential effects on cell proliferation were tested by MTT assay and on cell cycle and apoptosis were detected by flow cytometry (FACS. ResultsGuggulsterone significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner, with the maximal inhibition effect being observed with 100 μmol/L guggulsterone (81.9%±1.92%. FACS analysis indicated that guggulsterone-treated HepG2 cells were arrested in the G0/G1 phase. Guggulsterone also induced apoptosis of HepG2 cells (apoptotic %: 50 μmol/L, 24.91±2.41 and 75 μmol/L, 53.03±2.28. ConclusionGuggulsterone exerts anticancer effects on HepG2 hepatoma cells by inhibiting cell proliferation and inducing apoptosis. The anti-proliferative effect may be related to interference of the cell cycle.

  2. GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma

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    Toshihiko Inowa


    Full Text Available Side population (SP cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.

  3. [Effect of monoclonal antibodies against LI-cadherin on the proliferation of human hepatocellular carcinoma cells]. (United States)

    Chen, Xiao-ting; DU, Hong-yan; Yuan, Shao-fei; Wang, Sen-ming; Li, Ming


    To obtain monoclonal antibodies (mAb) against LI-cadherin and investigate their effects on the proliferation of human hepatocellular carcinoma cells. Balb/c mice were immunized with recombinant LI-cadherin, and hybridoma cell lines secreting monoclonal antibodies against LI-cadherin were established with routine cell fusion and subcloning approach. The specificity of these mAbs was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of the mAbs obtained on the growth of HepG2 cells was assessed using inverted microscope and MTT assay. Two hybridoma cell lines (F001 and F002) stably secreting specific mAbs were obtained. Western blot analysis showed that the two antibodies specifically recognized LI-cadherin antigen derived from human eucaryotic cells or tissue. Treatment of the HepG2 cells with the mAbs resulted in reduced viable cell number and changes in the cell morphologies, and the two mAbs inhibited the proliferation of HepG2 cells in a concentration-dependent manner (Pcells in vitro, which facilitates further study of the relationship between LI-cadherin and tumors.

  4. In Vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp-2 Cells

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    Michelle C. Búfalo


    Full Text Available Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2 cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis's antitumor action.

  5. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

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    Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: [Division of Pharmacology, National Institute of Health Sciences (Japan)


    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  6. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu


    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  7. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level. (United States)

    Liu, Deli; Xiong, Huan; Ellis, Angela E; Northrup, Nicole C; Dobbin, Kevin K; Shin, Dong M; Zhao, Shaying


    Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  8. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

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    Rodrigo Ramirez-Tagle


    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1 and 3′-bromo-3,4-dimethoxy-chalcone (CH2, over human hepatoma cells (HepG2 and Huh-7 and cultured mouse hepatocytes (HepM. Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i a caspase-dependent intrinsic pathway; and (ii by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  9. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells. (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar


    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  10. Progesterone receptor structure and protease activity in primary human endometrial carcinoma. (United States)

    Feil, P D; Clarke, C L; Satyaswaroop, P G


    Monoclonal antibodies were used to investigate progesterone receptor structure (isoforms) in 33 primary human endometrial tumors. The monoclonal antibodies recognized on protein blots two progesterone receptor proteins with molecular weights of 116,000 and 81,000. The Mr 116,000 protein appeared as a triplet, while a single band was found for the Mr 81,000 protein. The triplet/singlet structure was found in all progesterone receptor-positive tumors, regardless of the degree of tumor differentiation. Protease activity, which gave rise to a false-negative pattern on protein blots, was found in approximately one-half of the tumors in which it was investigated. Inclusion of a cocktail of protease inhibitors during sample preparation resulted in the maintenance of the triplet/singlet progesterone receptor structure. Mixing experiments using a progesterone receptor-rich human endometrial carcinoma (EnCa 101), which lacks protease activity, and protease-containing primary tumor homogenates indicated that the protease was leupeptin sensitive. Interestingly, while the proteolytic activity reduced or eliminated the triplet/singlet progesterone receptor structure seen on protein blot analysis, it did not affect progesterone receptor concentration measured by Scatchard analysis. Sample preparation in the presence of protease inhibitors is therefore a requisite for structural analysis of the progesterone receptor in endometrial tumors.

  11. Assessment of the Selenoprotein M (SELM over-expression on human hepatocellular carcinoma tissues by immunohistochemistry

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    E. Guerriero


    Full Text Available Selenium is an essential trace mineral of fundamental importance to human healthy and exerts its biological function through selenoproteins. In particular, Selenoprotein M (SELM is located in the endoplasmic reticulum and contains the common redox motif of cysteine-X-X-selenocysteine type. It attracts great attention due to its high expression in brain and its potential roles as antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our group found SELM over-expression  in human hepatocellular carcinoma (HCC cell lines. In this report some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV-related cirrhosis and HCC were immunohistochemically stained and SELM expression scoring was evaluated. Our results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. Therefore, we propose to use i SELM as putative marker for HCC as well as ii simple immunohistochemistry technique to distinguish between the different grades of malignancy. 

  12. Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma. (United States)

    Guidolin, Diego; Marinaccio, Christian; Tortorella, Cinzia; Annese, Tiziana; Ruggieri, Simona; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico


    Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites.

  13. Human embryonic stem cells and embryonal carcinoma cells have overlapping and distinct metabolic signatures.

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    Raed Abu Dawud

    Full Text Available While human embryonic stem cells (hESCs and human embryonal carcinoma cells (hECCs have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS. Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline or lower (e.g., glutamic acid, mannitol, malic acid, GABA in hESCs (H9 compared to hECCs (NTERA2, these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O(2 while oxidative phosphorylation (OXPHOS is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency.

  14. Extramedullary plasmacytoma imitating neoplasm of the gallbladder fossa after cholecystectomy. (United States)

    Majerović, Matea; Bogdanić, Branko; Drinković, Niksa; Kinda, Sandra Basić; Jakić-Razumović, Jasminka; Gasparović, Vladimir


    Extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow. They account for approximately 3% of plasma cell neoplasms and are most frequently located in the head and neck region. Five months after undergoing cholecystectomy, a 69-year-old patient presented with the pain under the right costal margin and a 12 kg weight loss. Computed tomography of the abdomen demonstrated irregular, vascular mass in the gallbladder fossa that dents towards the duodenum and the pylorus and lowers caudally to the hepatic flexure. His laboratory tests indicated normocytic anemia and showed elevated sedimentation rate. During operative procedure, a tumorous mass in the gallbladder fossa was found, inseparable of the peritoneum of the hepatoduodenal ligament and the IVb liver segment. Histopathological examination and immunohistochemical staining determined the diagnosis of the plasmacytoma. Total resection of the tumor was achieved and after 24-month follow-up patient showed no signs of local recurrence or dissemination of the disease.

  15. Postprandial gallbladder emptying in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Sonne, David P; Rehfeld, Jens F; Holst, Jens Juul


    fat, 93 g carbohydrate and 11 g protein; and iii) 40 g fat, 32 g carbohydrate and 3 g protein. Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP1, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin and gastrin were measured. Furthermore......OBJECTIVE: Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1(GCG)) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile......-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility. DESIGN AND METHODS...

  16. Expression pattern of RAGE and IGF-1 in the human fetal ovary and ovarian serous carcinoma. (United States)

    Poljicanin, Ana; Filipovic, Natalija; Vukusic Pusic, Tanja; Soljic, Violeta; Caric, Ana; Saraga-Babic, Mirna; Vukojevic, Katarina


    The expression pattern of RAGE and IGF-1 proteins in different ovarian cell lineages was histologically analyzed in six fetal, nine adult human ovaries, and nine serous ovarian carcinomas (OSC) using immunohistochemical methods. Mild expression of IGF-1 in ovarian surface epithelium (Ose) and oocytes in the 15-week human ovaries increased to moderate or strong in the stromal cells, oocytes and follicular cells in week 22. Occasional mild RAGE expression was observed in Ose during week 15, while strong expression characterized primordial follicles in week 22. In the reproductive human ovary, IGF-1 was mildly to moderately expressed in all ovarian cell lineages except in theca cells of the tertiary follicle where IGF-1 was negative. RAGE was strongly positive in the granulosa cells and some theca cells of the tertiary follicle, while negative to mildly positive in all cells of the secondary follicle. In the postmenopausal human ovary IGF-1 and RAGE were mildly expressed in Ose and stroma. In OSC, cells were strongly positive to IGF-1 and RAGE, except for some negative stromal cells. Different levels of IGF-1 and RAGE co-expression characterized fetal ovarian cells during development. In reproductive ovaries, IGF-1 and RAGE were co-localized in the granulosa and theca interna cells of tertiary follicles, while in postmenopausal ovaries and OSC, IGF-1 and RAGE were co-localized in Ose and OSC cells respectively. Our results indicate that intracellular levels of IGF-1 and RAGE protein might regulate the final destiny of the ovarian cell populations prior and during folliculogenesis, possibly controlling the metastatic potential of OSC as well. Copyright © 2015. Published by Elsevier GmbH.

  17. Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells. (United States)

    Dong, Wenjie; Shen, Ruizhe; Wang, Qi; Gao, Yabo; Qi, Xiaoguang; Jiang, He; Yao, Jingjing; Lin, Xiaolin; Wu, Yunlin; Wang, Lifu


    Telomere repeat binding factor 2 (TRF2) plays a key role in the protective activity of telomere and is overexpression in several kinds of solid cancer cells. However, the role of overexpressed TRF2 in colorectal carcinoma remains unclear. The aim of this study was to determine the expression of TRF2, address the mechanism of TRF2 overexpression in human colorectal carcinoma. In present study, we examined the expression of TRF2 in colorectal cancer tissues from 39 patients, peritumoral normal tissues from 21 patients, and colon carcinoma SW480 cell line by quantitative PCR, immunohistochemistry and western blot. After siRNA silencing TRF2 expression in SW480, tumorigenesis of TRF2 was tested by cell proliferation, soft agar assay, cytofluorimetric analysis and cytogenetic analysis. To discover transcription factor that mediated TRF2 expression, Chromatin Immunoprecipitation (Chip) Assay and Electrophoretic mobility shift assays (EMSA) were employed. Overexpression of TRF2 protein was detected in SW480 cells and 19 of 39 colorectal carcinoma tissues (49%), no overexpression was observed in 21 of 21 adjacent peritumoral normal colorectal tissues. After siRNA silencing TRF2 expression, the proliferation and colony formation of SW480 cells were significantly inhibited. Defective TRF2 induced apoptosis and increased chromosomal instability in SW480 cells, in which there were more end-to-end fusions and ring chromosomes. Chip assay and EMSA showed that transcription factor Sp1 is involved in upregulation of TRF2. These results indicate that TRF2 is overexpressed in colorectal carcinoma, Sp1 upregulates TRF2 expression, TRF2 inhibition reduces tumorigenesis of colorectal cancer, which suggests that TRF2 and SP1 may become new targets for the development of anti-cancer therapy in colorectal carcinoma.

  18. Lead, cadmium and zinc in mineral structure of deposits of the gallbladder in men and women


    Jerzy Kwapuliński; Bożena Ahnert; Barbara Brodziak-Dopierała; Błażej Szad; Brewczyński, Piotr Z.; Jarosław Rutkiewicz; Mariusz Bogunia; Jolanta Kowol


    Introduction: The former studies have shown the presence of As and Sb in deposits of the gallbladder. The aim of studies: The aim of the studies was to define the level of accumulation of Pb, Cd, Zn in deposits of the gallbladder as supplementary biological test for exposure assessment in a long run. Materials and methods: Pb, Cd and Zn content was investigated with inductive coupled plasmaatomic emission spectrometry were deposits of the gallbladder in men and women l...

  19. Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Wanner, Matthew R.; Karmazyn, Boaz [Indiana University School of Medicine, Riley Hospital for Children, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Fan, Rong [Indiana University School of Medicine, Riley Hospital for Children, Department of Pathology and Laboratory Medicine, Indianapolis, IN (United States)


    Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life-threatening bleeding. (orig.)

  20. Long-term survival after multidisciplinary therapy for residual gallbladder cancer with peritoneal dissemination: a case report. (United States)

    Kuga, Daisuke; Ebata, Tomoki; Yokoyama, Yukihiro; Igami, Tsuyoshi; Sugawara, Gen; Mizuno, Takashi; Yamaguchi, Junpei; Nagino, Masato


    Although surgical resection is the only curative treatment for gallbladder cancer (GBC), concomitant peritoneal dissemination is considered far beyond the scope of resection. We report a long-term survivor with a residual GBC with multiple peritoneal disseminations who underwent an extended resection after effective chemotherapy. A 59-year-old male underwent an open cholecystectomy for Mirizzi syndrome at a local hospital. Because of severe inflammation, the gallbladder was perforated during surgery, ending in a piecemeal resection. A pathological examination revealed GBC with positive margins, and the patient was referred to our hospital 1 month after surgery for further treatment. A multidetector-row computed tomography (MDCT) showed three hypoattenuated tumours: a tumour (3.9 cm) at the left medial segment corresponding to the gallbladder bed, a tumour (1.8 cm) around the hepatic flexure of the transverse colon, and a tumour (1.0 cm) at the stump of the cystic duct. Percutaneous needle biopsy was performed, which provided histologic evidence of adenocarcinoma. Thus, the patient had a rapidly progressive local relapse with limited peritoneal dissemination, labelled ycT3N0M1, stage IVB disease according to the UICC system. After the administration of 3 cycles of gemcitabine plus cisplatin combination chemotherapy, the size of all tumours and the CA19-9 level decreased significantly. Since the patient's general condition and liver function reserve were satisfactory, we decided the initial unresectable scenario to perform surgical therapy. After portal vein embolization, right hepatectomy, resection of the extrahepatic bile duct, partial duodenectomy, and partial colectomy were performed. Operative time was 555 min, and intraoperative blood loss was 1654 mL. Pathologic diagnosis of residual gallbladder carcinoma with peritoneal dissemination was confirmed, and the surgical margins were tumour-free. The patient was discharged on postoperative day 29, with a

  1. MiR-4282 suppresses proliferation and mobility of human colorectal carcinoma cells by targeting semaphorin 3E. (United States)

    Kang, Xing; Wang, Meng; Wang, Hao; Shen, Xiaofei; Guan, Wenxian


    MicroRNAs play an important role in cancer development. Deregulation of microRNAs can lead to tumorigenesis. Class 3 semaphorin, semaphorin 3E (Sema3E), has been shown to be implicated in tumor growth and metastasis. The role of miR-4282 in regulating colorectal carcinoma and its correlation to Sema3E remain uncertain. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the levels of miR-4282 and Sema3E in colorectal carcinoma cells and colorectal tumor tissues. Sema3E protein level in cell lines and human tissues was analyzed by western blot Transient transfections of miR-4282 inhibitor or mimics were conducted to silence or overexpress miR-4282. Sema3E siRNA was transfected to knockdown Sema3E in tumor cell lines. MTT assay was employed to measure colorectal tumor cell growth. Migration and invasion of the cells were examined by trans-well assays. Luciferase reporter assays were performed to confirm miR-4282 targeted at Sema3E. In the present study, reduced miR-4282 expression was observed in the colorectal carcinoma cell lines and human carcinoma tissues in comparison with normal human colon cells (Phuman colorectal tumor tissues (Pmobility (P<0.05). Sema3E was predicted as a target of miR-4282 in miRDB database. We found that miR-4282 overexpression significantly reduced luciferase activity of pRL-Sema3E-3'-UTR (P<0.05), but failed to alter the activity of pRL-sema3E-3'-UTR-mutation. Also, miR4282 overexpression suppressed Sema3E expression in the colorectal carcinoma cell lines. To further confirm the role of Sema3E suppression in the function of the colorectal carcinoma cells by miR-4282, HT29 and HCT116 cells were transfected with Sema3E siRNA. We found that cell growth, migration and invasion of HT29 and HCT116 cells were dramatically inhibited by Sema3E knockdown (P<0.05). Our findings suggested that miR-4282 is a tumor suppressor in colorectal carcinoma cells and exerted its inhibitory effect on the tumor cells

  2. Effect of narcotic premedication of scintigraphic evaluation of gallbladder perforation

    Energy Technology Data Exchange (ETDEWEB)

    Sefczek, D.M.; Sharma, P.; Isaacs, G.H.; Brodmerkel, G.J. Jr.; Adatepe, M.H.; Powell, O.M.; Nichols, K.


    A case of gallbladder perforation is presented in which a small bile leak was demonstrated by cholescintigraphy while the patient was receiving meperidine, but not after meperidine was discontinued. The scintigrams obtained during meperidine therapy also showed a pattern of bile-duct obstruction. It is suggested that increased biliary pressure secondary to meperidine admininstration permitted visualization of the leak. Use of narcotic drugs may be a useful pharmocologic intervention in cases of peritonitis due to small obscure bile leaks.

  3. Expression of the human sodium/iodide symporter (hNIS) in xenotransplanted human thyroid carcinoma

    NARCIS (Netherlands)

    Smit, J.W.A.; Schröder - van der Elst, J.P.; Karperien, M.; Que, I.; Romijn, J.A.; Heide, van der D.


    The uptake of iodide in thyroid epithelial cells is mediated by the sodium/iodide symporter (NIS). The uptake of iodide is of vital importance for thyroid physiology and is a prerequisite for radioiodine therapy in thyroid cancer. Loss of iodide uptake due to diminished expression of the human NIS

  4. Experience in laparoscopic cholecystectomy for complicated gallbladder disease

    Directory of Open Access Journals (Sweden)

    LI Xueyuan


    Full Text Available ObjectiveTo investigate the approach to laparoscopic cholecystectomy (LC in the treatment of complicated gallbladder disease. MethodsA retrospective analysis was performed on the clinical data of 81 patients with complicated gallbladder disease admitted to the Department of General Surgery in our hospital from August 2007 to November 2013, including 66 cases of acute cholecystitis, 14 cases of atrophic cholecystitis, and 1 case of Mirizzi syndrome. All laparoscopic operations were completed using the aspirating dissector and ultrasonic knife and lasted for 1.5-3 h. ResultsLC was successfully completed in 79 cases. One case had common hepatic duct injury during operation, which was treated by laparoscopic suture repair; one case had intraoperative bleeding and was converted to laparotomy; one case was suspected of having Mirizzi syndrome before operation and was converted to laparotomy after the syndrome was confirmed during operation. ConclusionLaparoscopic cholecystectomy is safe and feasible in the treatment of complicated gallbladder disease. The key to successful treatment is preoperative evaluation of this disease, intraoperative use of aspirating dissector and ultrasonic knife for dissecting the Calot triangle, antegrade resection combined with retrograde resection, and total resection combined with partial resection, which can effectively avoid intraoperative hemorrhage and bile duct injury.

  5. Clonorcis sinensis eggs are associated with calcium carbonate gallbladder stones. (United States)

    Qiao, Tie; Ma, Rui-hong; Luo, Zhen-liang; Yang, Liu-qing; Luo, Xiao-bing; Zheng, Pei-ming


    Calcium carbonate gallbladder stones were easily neglected because they were previously reported as a rare stone type in adults. The aim of this study was to investigate the relationship between calcium carbonate stones and Clonorchis sinensis infection. A total of 598 gallbladder stones were studied. The stone types were identified by FTIR spectroscopy. The C. sinensis eggs and DNA were detected by microscopic examination and real-time fluorescent PCR respectively. And then, some egg-positive stones were randomly selected for further SEM examination. Corresponding clinical characteristics of patients with different types of stones were also statistically analyzed. The detection rate of C. sinensis eggs in calcium carbonate stone, pigment stone, mixed stone and cholesterol stone types, as well as other stone types was 60%, 44%, 36%, 6% and 30%, respectively, which was highest in calcium carbonate stone yet lowest in cholesterol stone. A total of 182 stones were egg-positive, 67 (37%) of which were calcium carbonate stones. The C. sinensis eggs were found adherent to calcium carbonate crystals by both light microscopy and scanning electron microscopy. Patients with calcium carbonate stones were mainly male between the ages of 30 and 60, the CO2 combining power of patients with calcium carbonate stones were higher than those with cholesterol stones. Calcium carbonate gallbladder stones are not rare, the formation of which may be associated with C. sinensis infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Sonographic evaluation of gallbladder motility in children with chronic functional constipation. (United States)

    Mehra, Rakesh; Sodhi, Kushaljit Singh; Saxena, Akshay; Thapa, B R; Khandelwal, Niranjan


    Studies in adults suggest that constipation may not be a purely colonic pathology and may be a component of a generalized gastrointestinal (GI) motor disorder in which proximal GI motility can be impaired. Pediatric data are scarce, and the natural history of the disorder remains undefined. We aimed to evaluate gallbladder motility in a subset of Asian children with chronic functional constipation. Abdominal ultrasound was performed on 105 children, including 55 patients (aged 3 to 13 years) with chronic functional constipation who met the inclusion criteria and 50 age- and gender-matched controls. The gallbladder contractility index was calculated based on the preprandial and postprandial gallbladder areas. Preprandial and postprandial values for gallbladder volume and wall thickness were evaluated. The mean value of the contractility index for the patients (15.77±24.68) was significantly lower than the mean value for the controls (43.66±11.58) (p=0.001). The mean postprandial gallbladder volumes and areas were larger in children with gallbladder hypomotility (pconstipation (4.8 months) was significantly higher (p=0.004) in the children with gallbladder hypomotility. Gallbladder motility is significantly impaired in children with chronic functional constipation. This study contributes to the understanding of the underlying pathophysiology, which will enable advancement in and improved management of children with chronic constipation and associated gallbladder hypomotility.

  7. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway. (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei


    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  8. Comparison between ultrasonographic and clinical findings in 43 dogs with gallbladder mucoceles. (United States)

    Choi, Jihye; Kim, Ahyoung; Keh, Seoyeon; Oh, Juyeon; Kim, Hyunwook; Yoon, Junghee


    Cholecystectomy is the current standard recommended treatment for dogs with gallbladder mucoceles. However, medical management with monitoring has also been recommended for asymptomatic dogs. The purpose of this retrospective study was to compare ultrasonographic patterns of gallbladder mucoceles with clinical disease status in a group of dogs. For each included dog, the ultrasonographic pattern of the mucocele was classified into one of six types: type 1, immobile echogenic bile; type 2, incomplete stellate pattern; type 3, typical stellate pattern; type 4, kiwi like pattern and stellate combination; type 5, kiwi like pattern with residual central echogenic bile; and type 6, kiwi like pattern. A total of 43 dogs were included. Twenty-four dogs, including 11 dogs with gallbladder rupture, were symptomatic. Nineteen dogs were asymptomatic. Cholecystectomy (n = 19), medical therapy (n = 17), or monitoring (n = 6) treatments were applied according to clinical signs and owners' requests. One dog suspected of having gallbladder rupture was euthanized. Frequencies of gallbladder mucocele patterns were as follows: type 1 = 10 (23%), type 2 = 13 (30%), type 3 = 5 (12%), type 4 = 11 (26%), type 5 = 4 (9%), and type 6 = 0. In dogs with gallbladder rupture, type 2 (8/13) was the most common. No significant correlations were found between ultrasonographic patterns of gallbladder mucoceles and clinical disease status or gallbladder rupture. Findings indicated that ultrasonographic patterns of gallbladder mucoceles may not be valid bases for treatment recommendations in dogs. © 2013 American College of Veterinary Radiology.

  9. MicroRNA-328 enhances cellular motility through posttranscriptional regulation of PTPRJ in human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Luo X


    Full Text Available Xiaoling Luo,1 Shiyan Yang,2 Chuanwen Zhou,1 Feng Pan,1 Qianjun Li,1 Shijie Ma1 1Department of Gastroenterology, Huai’an First People’s Hospital, Nanjing Medical University, 2Department of Gastroenterology, Huai’an Hospital Affiliated to Xuzhou Medical College and Huai’an Second People’s Hospital, Huai’an, Jiangsu, People’s Republic of China Objective: Interaction between microRNA (miR-328 and PTPRJ (protein tyrosine phosphatase, receptor type, J has been reported to be responsible for miR-328-dependent increase in epithelial cancer cell proliferation. However, the role of miR-328 and PTPRJ in hepatocellular carcinoma (HCC remains unclear. The aim of this study was to investigate the clinical significance of miR-328 and/or PTPRJ expression in human HCC and determine their precise biological functions in this malignancy. Methods: Expression levels of miR-328 and PTPRJ messenger RNA (mRNA in 100 pairs of HCC and adjacent noncancerous tissues were detected using quantitative real-time reverse transcription polymerase chain reaction. The associations between miR-328 and/or PTPRJ expression and various clinicopathological features of HCC patients were further statistically assessed. Then, the functions of miR-328 and PTPRJ in migration and invasion of two human HCC cell lines were determined by transwell assays. Results: miR-328 and PTPRJ mRNA expression levels were markedly upregulated and downregulated in HCC tissues, respectively, compared to adjacent noncancerous tissues. Notably, the upregulation of miR-328 in HCC tissues was significantly correlated with the downregulation of PTPRJ mRNA in HCC tissues (r=-0.362, P=0.01. In addition, miR-328-high and/or PTPRJ-low expression were found to be closely correlated with high Edmondson–Steiner grading (all P<0.05 and advanced tumor-node-metastasis stage (all P<0.05. Moreover, the restoration of miR-328 dramatically promoted HCC cell migration and invasion by repressing PTPRJ expression

  10. Detection of human papillomavirus in squamous cell carcinoma arising from dermoid cysts. (United States)

    Chiang, An-Jen; Chen, Di-Rong; Cheng, Jiin-Tsuey; Chang, Tsung-Hsien


    Primary squamous cell carcinoma (SCC) of the ovary in humans is rare. Most cases represent a malignant transformation of ovarian teratoma, Brenner tumor, or endometriosis. The etiology of this cancer remains largely unknown. Human papillomavirus (HPV) infection is a critical factor that induces tumor formation, particularly cervical cancer. Therefore, this study aimed to evaluate the association of HPV with malignant transformation of mature cystic teratoma (MCT) into SCC of the ovary. The samples included four formalin-fixed paraffin-embedded SCC-MCT tissues and their adjacent tissues from the cervix to the ovaries, 12 cases of benign teratoma ovarian tissues (dermoid tissues), and 11 cases of benign nonteratoma ovarian tissues (nondermoid tissues). The two squamous carcinoma tissues of the cervix were used as control samples. HPV was detected by immunohistochemistry (IHC) with anti-HPV capsid or E6 (HPV type 16/18) antibodies and in situ hybridization (ISH) with three sets of genotyping probes, HPV types 6/11, 16/18, and 31/33. IHC revealed HPV infection associated with the four cases of SCC-MCT and the two cases of control cervical cancer samples. Importantly, HPV was also detected in adjacent reproductive tissues of the SCC-MCT cases, which suggested that the viral particles might spread in an ascending route through the fallopian tubes, endometrium, endocervix, and cervix to the ovaries. ISH revealed HPV type 16/18 in all SCC-MCT cases and HPV type 31/33 in two, with no HPV type 6/11 in any SCC-MCT cases. However, compared with the SCC-MCT cases, the lower detection rates of HPV in dermoid cysts and nondermoid tissues suggested that HPV might not be associated with normal ovarian tissues or benign ovarian teratomas. Our data suggest that high-risk HPV infection might be a causal factor that induces malignant transformation of MCT into SCC of the ovary, although further investigation is still required. Copyright © 2015. Published by Elsevier B.V.

  11. Cyclic AMP Induces Transforming Growth Factor β2 Gene Expression and Growth Arrest in the Human Androgen-Independent Prostate Carcinoma Cell Line PC-3

    National Research Council Canada - National Science Library

    Yung-Jue Bang; Seong-Jin Kim; David Danielpour; Michael A. O'Reilly; Kyung Young Kim; Charles E. Myers; Jane B. Trepel


    .... To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines...

  12. Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3

    National Research Council Canada - National Science Library

    Y J Bang; S J Kim; D Danielpour; M A O'Reilly; K Y Kim; C E Myers; J B Trepel


    .... To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines...

  13. Cyclic AMP-independent secretion of mucin by SW1116 human colon carcinoma cells. Differential control by Ca2+ ionophore A23187 and arachidonic acid

    National Research Council Canada - National Science Library

    Yedgar, S; Eidelman, O; Malden, E; Roberts, D; Etcheberrigaray, R; Goping, G; Fox, C; Pollard, H B


    The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients...

  14. Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines. (United States)

    Lorente, Cristina; Arias, José L; Cabeza, Laura; Ortiz, Raúl; Prados, José C; Melguizo, Consolación; Delgado, Ángel V; Clares-Naveros, Beatriz


    Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents. © 2018 Royal Pharmaceutical Society.

  15. Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Hirako, Yoshiaki, E-mail: [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Yonemoto, Yuki; Yamauchi, Tomoe [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Nishizawa, Yuji; Kawamoto, Yoshiyuki [Department of Biomedical Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Owaribe, Katsushi [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan)


    Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to basement membranes. For the first time, we present a method to prepare a fraction from human cultured cells that are highly enriched in hemidesmosomal proteins. Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of hemidesmosomes was observed when these cells were cultured for more than 10 days in a commercial serum-free medium without supplemental calcium. Electron microscopy demonstrated that numerous electron-dense adhesion structures were present along the basal cell membranes of DJM-1 cells cultured under the aforementioned conditions. After removing cellular materials using an ammonia solution, hemidesmosomal proteins and deposited extracellular matrix were collected and separated by electrophoresis. There were eight major polypeptides, which were determined to be plectin, BP230, BP180, integrin α6 and β4 subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we designated this preparation as a hemidesmosome-rich fraction. This fraction contained laminin-332 exclusively in its unprocessed form, which may account for the promotion of laminin deposition, and minimal amounts of Lutheran blood group protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich fraction would be useful not only for biological research on hemidesmosomes but also for developing a serum test for patients with blistering skin diseases. - Highlights: • A defined condition promoted accumulation of hemidesmosomes in human cultured cells. • A fraction isolated from the cells contained eight major polypeptides. • The polypeptides were the five major hemidesmosome proteins and laminin-332. • The cultured cells deposited laminin-332 in its unprocessed form under the condition. • We report a method to prepare a fraction highly enriched in hemidesmosome proteins.

  16. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han


    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  17. Mutational spectra of aflatoxin B1in vivo establish biomarkers of exposure for human hepatocellular carcinoma. (United States)

    Chawanthayatham, Supawadee; Valentine, Charles C; Fedeles, Bogdan I; Fox, Edward J; Loeb, Lawrence A; Levine, Stuart S; Slocum, Stephen L; Wogan, Gerald N; Croy, Robert G; Essigmann, John M


    Aflatoxin B 1 (AFB 1 ) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB 1 -DNA adducts in hepatocytes seeds a population of mutations, mainly G:C→T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Responding to a need for early-onset evidence predicting disease development, highly accurate duplex sequencing was used to monitor acquisition of high-resolution mutational spectra (HRMS) during the process of hepatocarcinogenesis. Four-day-old male mice were treated with AFB 1 using a regimen that induced HCC within 72 wk. For analysis, livers were separated into tumor and adjacent cellular fractions. HRMS of cells surrounding the tumors revealed predominantly G:C→T:A mutations characteristic of AFB 1 exposure. Importantly, 25% of all mutations were G→T in one trinucleotide context (C G C; the underlined G is the position of the mutation), which is also a hotspot mutation in human liver tumors whose incidence correlates with AFB 1 exposure. The technology proved sufficiently sensitive that the same distinctive spectrum was detected as early as 10 wk after dosing, well before evidence of neoplasia. Additionally, analysis of tumor tissue revealed a more complex pattern than observed in surrounding hepatocytes; tumor HRMS were a composite of the 10-wk spectrum and a more heterogeneous set of mutations that emerged during tumor outgrowth. We propose that the 10-wk HRMS reflects a short-term mutational response to AFB 1 , and, as such, is an early detection metric for AFB 1 -induced liver cancer in this mouse model that will be a useful tool to reconstruct the molecular etiology of human hepatocarcinogenesis.

  18. In vitro anti-proliferative activity of clove extract on human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    A. Karimi


    Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

  19. Molecular basis of arsenite (As+3-induced acute cytotoxicity in human cervical epithelial carcinoma cells

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    Muhammad Nauman Arshad


    Full Text Available Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3 on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml. Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3 resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

  20. Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium. (United States)

    Cartularo, Laura; Laulicht, Freda; Sun, Hong; Kluz, Thomas; Freedman, Jonathan H; Costa, Max


    Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Human papillomavirus genotypes in invasive cervical squamous cell carcinoma in Trinidad Genotipos de virus de los papilomas humanos en carcinoma cervicouterino escamocelular invasor en Trinidad

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    Felicia Hosein


    Full Text Available OBJECTIVE: To determine the relative contribution of known high-risk human papillomavirus (HPV genotypes to the occurrence of cervical cancers in Trinidad. METHODS: The distribution of HPV genotypes in cases of invasive cervical squamous cell carcinoma in Trinidad was investigated. This study was a follow-up to an investigation of HPV genotypes in 310 nonsymptomatic women in Trinidad. The latter study showed that cervical HPV prevalence and heterogeneity of genotypes were high in the study population; notably, the genotypes targeted by the available HPV prophylactic vaccines were not the most common types. RESULTS: The current study of 85 cases of invasive cervical squamous cell carcinomas demonstrated that the previously observed heterogeneity in HPV genotype distribution is lost in cases of invasive cervical cancer, with the vaccine-targeted HPV types HPV 16 and HPV 18 becoming the most prevalent. CONCLUSIONS: HPV 16 and HPV 18 were the primary HPV genotypes associated with cases of invasive squamous cell carcinoma in the current Trinidad study. This strong association leads us to conclude that the HPV vaccines targeting HPV 16 and HPV 18 may contribute to reducing the cervical cancer burden in Trinidad.OBJETIVO: Determinar la contribución relativa de los diferentes genotipos de virus de los papilomas humanos (VPH conocidos como de alto riesgo para la aparición de cáncer cervicouterino en Trinidad. MÉTODOS: Se investigó la distribución de los genotipos de VPH en casos de carcinoma cervicouterino escamocelular invasor en Trinidad. Este estudio fue la continuación de una investigación de los genotipos de VPH presentes en 310 mujeres asintomáticas en Trinidad. Este último estudio reveló altas prevalencia de VPH en el cuello uterino y heterogeneidad de los genotipos en la población del estudio; cabe destacar que los genotipos a los que se dirigen las vacunas preventivas de la infección por VPH disponibles no fueron los tipos m

  2. Gallbladder ejection fraction declines with age in patients undergoing cholecystectomy for acalculous biliary symptoms but has low accuracy in the prediction of gallbladder pathology. (United States)

    Jones, Aled; Shahtahmassebi, Golnaz; Stell, David


    Hepatobiliary Iminodiacetic Acid (HIDA) scan provides a technique to quantify gallbladder ejection fraction (EF) in patients suffering acalculous biliary colic (ACBC). We wished to evaluate the accuracy of EF in the prediction of gallbladder pathology in patients undergoing cholecystectomy. Data were retrieved from a database of patients referred for HIDA scan for ACBC, including EF and the pathological outcome of those undergoing cholecystectomy, and compared to normal values obtained from a review of related studies. Significant associations were demonstrated by chi-square, Mann-Whitney test, and linear regression. The predictive accuracy of different cut-offs of EF was demonstrated by the ROC curve analysis. Of 83 patients referred for HIDA scan for ACBC, 41 underwent cholecystectomy. The median EF of this group (33%) was significantly lower than the composite normal median value from previous studies (56%). Thirty-two patients revealed evidence of gallbladder pathology. The EF declined with age (coefficient = -0.51, 95% CI = -0.99 to -0.33), but the median value did not differ between those with gallbladder pathology (34%) and those with normal gallbladders (29%). Although an EF cut-off of 35% had the greatest accuracy in the prediction of pathology of those tested (0.56), the poor negative predictive value (23.5%) was a major contributor to its low accuracy. Although patients with ACBC have reduced gallbladder EF compared to the normal population, its quantitative assessment is of limited value in the prediction of gallbladder pathology.

  3. Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma.


    Wilczynski, S P; Lin, B T; Xie, Y; Paz, I.B.


    Human papillomavirus (HPV) DNA has been detected in approximately 15% of squamous cell carcinomas (SCCs) of the head and neck. Recent studies have shown a predilection of HPV for certain anatomical sites, especially the tonsillar region, with viral DNA identified in approximately 60% of SCCs of the Waldeyer's tonsillar ring. This study was undertaken to determine whether there are differences in morphology or in oncogene expression in SCC of the tonsil with and without detectable HPV DNA. Twe...

  4. The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells


    Yang, In-Hyoung; Shin, Ji-Ae; Kim, Lee-Han; Kwon, Ki Han; CHO, SUNG-DAE


    In the present study, the apoptotic effect of pycnogenol and its molecular mechanism in human oral squamous cell carcinoma HSC-3 cells were investigated. Pycnogenol significantly inhibited the viability of HSC-3 cells and suppressed neoplastic cell transformation in HSC-3 cells and TPA-treated JB6 cells. It caused caspase-dependent apoptosis evidenced by the increase in cleaved poly (ADP-ribose) polymerase and caspase 3 in a dose-dependent manner. Pycnogenol increased Bak protein by enhancing...

  5. Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells


    Carraz, Maëlle; Lavergne, C.; Jullian, Valérie; Wright, M.; Gairin, J E; de la Cruz, M. G.; Bourdy, Geneviève


    Ethnopharmacological relevance: The high incidence of human hepatocellular carcinoma (HCC) in Peru and the wide use of medicinal plants in this country led us to study the activity against HCC cells in vitro of somes species used locally against liver and digestive disorders. Materials and methods: Ethnopharmacological survey: Medicinal plant species with a strong convergence of use for liver and digestive diseases were collected fresh in the wild or on markets, in two places of Peru: Chiclay...

  6. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest.

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    Md Sultan Ahamad

    Full Text Available A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01 with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001 dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation.

  7. Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth, angiogenesis, invasion, and metastasis. (United States)

    Li, Wendong; Ding, Fang; Zhang, Liyong; Liu, Zhongmin; Wu, Yu; Luo, Aiping; Wu, Min; Wang, Mingrong; Zhan, Qimin; Liu, Zhihua


    Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy. We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor. Both transfection of stefin A and treatment with 10 micromol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice. Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.

  8. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma. (United States)

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei


    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  9. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells. (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu


    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells. (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria


    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  11. Antiproliferative effect of chitosan-added kimchi in HT-29 human colon carcinoma cells. (United States)

    Kong, Chang-Suk; Bahn, Young-Eun; Kim, Boh-Kyung; Lee, Kang-Yoon; Park, Kun-Young


    The anticancer effects of chitosan-added kimchi were investigated by using an in vitro cellular system with HT-29 human colon carcinoma cells. Two different kinds of chitosan-soluble chitosan with a 90% degree of deacetylation and 3 cps viscosity and nonsoluble chitosan with a 95% degree of deacetylation and 22 cps viscosity-were used as sub-ingredients to increase anticancer effects of kimchi. The soluble chitosan-added kimchi (SK) and nonsoluble chitosan-added kimchi (NK) were stronger growth inhibitors in HT-29 cells than the control kimchi (CK) according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the growth inhibition test. Treatment with SK and NK induced apoptosis, as determined by 4,6-diamidino-2-phenylindole staining, and resulted in the up-regulation of Bax expression and down-regulation of Bcl-2, cIAP-1, cellular inhibitor of apoptosis-2, cyclooxygenase-2, inhibitory nitric oxide synthase, and nuclear factor kappaB (NF-kappaB) expressions when compared to CK. The antiproliferative and anti-apoptotic effects appeared to be more pronounced in the cells treated with NK. The antiproliferative effects of the chitosan-added kimchi appeared to be associated with the induction of apoptosis through NF-kappaB or an NF-kappaB-dependent pathway. These results suggest that chitosan has potential to be a valuable active ingredient in functional kimchi products with anticancer effects.

  12. Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line

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    Chen Show-Li


    Full Text Available Abstract Background Troglitazone (TGZ is a potential anticancer agent. Little is known about the effect of this agent on cancer cell migration. Methods Human ovarian carcinoma cell line, ES-2 cells were treated with various concentrations of TGZ. Cell migration was evaluated by wound-healing and Boyden chamber transwell experiments. PPARγ expression was blocked by PPARγ small interfering RNA. The effects of TGZ on phosphorylation of FAK, PTEN, Akt were assessed by immunoblotting using phospho-specific antibodies. The cellular distribution of paxillin, vinculin, stress fiber and PTEN was assessed by immunocytochemistry. Results TGZ dose- and time-dependently impaired cell migration through a PPARγ independent manner. TGZ treatment impaired cell spreading, stress fiber formation, tyrosine phosphorylation of focal adhesion kinase (FAK, and focal adhesion assembly in cells grown on fibronectin substratum. TGZ also dose- and time-dependently suppressed FAK autophosphorylation and phosphorylation of the C-terminal of PTEN (a phosphatase. At concentration higher than 10 μM, TGZ caused accumulation of PTEN in plasma membrane, a sign of PTEN activation. Conclusion These results indicate that TGZ can suppress cultured ES-2 cells migration. Our data suggest that the anti-migration potential of TGZ involves in regulations of FAK and PTEN activity.

  13. The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

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    Zheng Zhi


    Full Text Available Autophagy is a conserved catabolic process, which functions in maintenance of cellular homeostasis in eukaryotic cells. The self-eating process engulfs cellular long-lived proteins and organelles with double-membrane vesicles, and forms a so-called autophagosome. Degradation of contents via fusion with lysosome provides recycled building blocks for synthesis of new molecules during stress, e.g. starvation. Peiminine is a steroidal alkaloid extracted from Fritillaria thunbergii which is widely used in Traditional Chinese Medicine. Previously, peiminine has been identified to induce autophagy in human colorectal carcinoma cells. In this study, we further investigated whether peiminine could induce autophagic cell death via activating autophagy-related signaling pathway AMPK-mTOR-ULK by promoting SQSTM1(P62. Xenograft tumor growth in vivo suggested that both peiminine and starvation inhibit the growth of tumor size and weight, which was prominently enhanced when peiminine and starvation combined. The therapeutical effect of peiminine in cancer treatment is to be expected.

  14. Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism

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    Cuilan Hou


    Full Text Available Isoliquiritigenin (ISL, a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113 were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS generation, Gelatin zymography assay for matrix metalloproteinase (MMP activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax. Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism.

  15. Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism (United States)

    Hou, Cuilan; Li, Wenguang; Li, Zengyou; Gao, Jing; Chen, Zhenjie; Zhao, Xiqiong; Yang, Yaya


    Isoliquiritigenin (ISL), a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC) is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL) on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113) were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM) analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS) generation, Gelatin zymography assay for matrix metalloproteinase (MMP) activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax). Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism. PMID:28203317

  16. No evidence of human papilloma virus infection in basal cell carcinoma

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    Yalda Nahidi


    Full Text Available Background: Basal cell carcinoma (BCC is the most common skin cancer among whites, and several risk factors have been discussed in itsdevelopment and progress. Detection of human papilloma virus (HPV deoxyribonucleic acid (DNA BCCs in some studies suggests that the virus may play a role in the pathogenesis of this disease. Several molecular studies showed conflicting reports. Aims: The purpose of this study was to investigate the association between HPV and BCC using polymerase chain reaction (PCR. Materials and Methods: HPV DNA detection was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin samples around the lesions by PCR using GP5+/GP6+ primers. Results: HPV DNA was not found in any of the 42 samples of BCC, and only one normal skin sample around the lesions was positive for HPV DNA by PCR. Conclusion: In this study, no statistically significant difference was seen between the presence of HPV DNA in BCC and normal skin around the lesion, and HPV is not likely to have an important role in pathogenesis of BCC.

  17. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

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    Miao Yun

    Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

  18. Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

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    Li Bin


    Full Text Available Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging. Results PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control. Conclusions and Clinical Relevance PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.

  19. Tributyltin induces mitochondrial fission through NAD-IDH dependent mitofusin degradation in human embryonic carcinoma cells. (United States)

    Yamada, Shigeru; Kotake, Yaichiro; Nakano, Mizuho; Sekino, Yuko; Kanda, Yasunari


    Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure.

  20. [Study of inhibitory effect of extracts from Actinidia arguta on human carcinoma of esophagus cells]. (United States)

    Zhang, Li; Guo, Hong-Li; Tian, Lin; Cao, Shu-Fen; Du, Chang-Hai


    To study the inhibitory effect of extracts from Actinidia arguta by n-butyl alcohol on human carcinoma of esophagus cells (Eca-109) and Its mechanism. MTT colonmetric assay was used to examine the growth inhibitory of concentration-effect (1 microg/ml, 10 microg/ml,100 microg/ml) and time-effect (24 h, 48 h, 72 h) of extracts from Actinidia arguta by n-butyl alcohol on Eca-109 cells. TUNEL test were performed to observe the apoptosis induced by the extracts (1 microg/ml, 10 microg/ml, 100 microg/ml) on Eca-109 cells. The inhibitory effect of the extracts on Eca-109 cells increased in a dose-time Manner and the highest rate of inhibition was 87.2%. The extracts could significantly induce apoptosis of Eca-109 cells, but in control group, apoptosis wasn't observed. The extracts from Actinidia arguta by n-butyl alcohol have good inhibitory effect on Eca-109 cells.

  1. Spatial distribution of mast cells and macrophages around tumor glands in human breast ductal carcinoma. (United States)

    Tamma, Roberto; Guidolin, Diego; Annese, Tiziana; Tortorella, Cinzia; Ruggieri, Simona; Rega, Serena; Zito, Francesco A; Nico, Beatrice; Ribatti, Domenico


    Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

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    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

  3. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja


    Full Text Available BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  4. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja


    Full Text Available Background Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. Methods During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. Results Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. Conclusion The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  5. Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo. (United States)

    Koci, Lenka; Chlebova, Katarina; Hyzdalova, Martina; Hofmanova, Jirina; Jira, Miroslav; Kysela, Petr; Kozubik, Alois; Kala, Zdenek; Krejci, Pavel


    Apoptosis inhibitor 5 (API-5) is a 55 kDa nuclear protein with potent anti-apoptotic signaling in tumor cells in vitro. In this study, we analyzed the expression of the API-5 protein in vivo in a broad spectrum of human carcinomas, including those of the colon, lung, liver, kidney, pancreas, stomach and esophagus using tumor tissues obtained during tumor resection. The results showed significant upregulation of API-5 expression in biopsies of lung (23%, n=13) and colorectal tumors (33%, n=27) in comparison with biopsies from the adjacent normal tissue. Colon cancer biopsies were used to study the cell populations with an upregulated level of expression of API-5 more closely. Using a magnetic bead-based selection for the epithelial cell marker EpCAM, we purified epithelial cells from the tumor and control tissues and analyzed these cells for API-5 expression by western immunoblotting. We observed that EpCAM-positive tumor cells expressed API-5 in all three colorectal cancer cases tested, in contrast to the control EpCAM-positive and EpCAM-negative cells isolated from the control or tumor tissues. These data suggest that the expression of the API-5 protein is upregulated in tumor epithelial cells and may serve as a prognostic marker in colorectal cancer.

  6. CD200-expressing human basal cell carcinoma cells initiate tumor growth. (United States)

    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K


    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  7. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase

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    Haberkorn, Uwe; Khazaie, Khashayarsha; Morr, Iris; Altmann, Annette; Mueller, Markus; Kaick, Gerhard van


    Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r=0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.

  8. Piperine Triggers Apoptosis of Human Oral Squamous Carcinoma Through Cell Cycle Arrest and Mitochondrial Oxidative Stress. (United States)

    Siddiqui, Sahabjada; Ahamad, Md Sultan; Jafri, Asif; Afzal, Mohd; Arshad, Md


    Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine. Results showed that various concentrations (25-300 μM) of piperine exposure reduced the cell viability of KB cells significantly (P Piperine induced significant (P piperine stimulated cell death by inducing loss of MMP, and caspase-3 activation. Cell cycle study revealed that piperine arrested the cells in G2/M phase and decreased the DNA content. Findings of this study suggest the efficacy of piperine in inducing cell death via the decrease in MMP and ROS liberation followed by caspase-3 activation and cell cycle arrest. Further assessment of the anticancer potency of piperine is needed for anticancer drug development.

  9. Pheophorbide a mediated photodynamic therapy against human epidermoid carcinoma cells (A431) (United States)

    Chen, Yi-Chun; Li, Wen-Tyng


    The objective of this study was to characterize the death mechanism of human epidermoid carcinoma cells (A431) triggered by photodynamic therapy (PDT) with pheophorbide a. First of all, significant inhibition on the survival of A431 cells (cancer cells selectively. Mitochondria were the main target sites where pheophorbide a accumulated. Formation of reactive oxygen species (ROS) was detected after PDT. Addition of antioxidant N-Acetyl cysteine prevented ROS production and increased cell survival thereafter. The decrease in cellular ATP level was also observed at 6 hrs after PDT. Typical apoptotic cellular morphology and a collapse of mitochondrial membrane potential occurred after PDT. The loss of mitochondrial membrane potential led to the release of cytochrome c from the mitochondria to the cytosol, followed by activation of caspase-9 and caspase-3. The activation of caspase-3 resulted in poly(ADP-ribose) polymerase (PARP) cleavage in A431 cells, followed by DNA fragmentation. In conclusion, the results demonstrated that pheophorbide a possessed photodynamic action against A431 cells, mainly through apoptosis mediated by mitochondrial intrinsic pathway triggered by ROS.

  10. Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells. (United States)

    Kuznetsov, Andrey V; Javadov, Sabzali; Saks, Valdur; Margreiter, Raimund; Grimm, Michael


    Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca2+ are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria. In addition, mitochondria-mitochondria interactions can produce wave propagations of mitoROS flashes and ΔΨm collapses in cancer cells similar to phenomena of ROS-induced ROS release (RIRR). Our data suggest that in cancer cells RIRR, activation of mitoROS flashes and mitochondrial depolarization may involve participation of extramitochondrial-ROS produced either by individual mitochondria and/or by neighboring mitochondria. This could represent general mechanisms in ROS-ROS signaling with suggested role in both mitochondrial and cellular physiology and signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma. (United States)

    Belvisi, Valeria; Martellucci, Salvatore; Garbuglia, Anna Rosa; Del Borgo, Cosmo; Martellucci, Stanislao; Baiocchini, Andrea; Manicone, Anna Maria; Bagni, Oreste; Mastroianni, Claudio Maria; Gallo, Andrea


    The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

  12. Ethanolic Extracts of Pluchea indica Induce Apoptosis and Antiproliferation Effects in Human Nasopharyngeal Carcinoma Cells

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    Chiu-Li Kao


    Full Text Available Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04 in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins.

  13. Prevalence of human papillomavirus in laryngeal and hypopharyngeal squamous cell carcinomas in northern Spain. (United States)

    Rodrigo, Juan P; Hermsen, Mario A; Fresno, Manuel F; Brakenhoff, Ruud H; García-Velasco, Fabian; Snijders, Peter J F; Heideman, Daniëlle A M; García-Pedrero, Juana M


    Recent studies support a role for human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (SCCs); however, the significance of HPV in non-oropharyngeal head and neck cancers is uncertain. The aim of this study was to determine the prevalence of HPV in a large cohort of laryngeal and hypopharyngeal SCCs in northern Spain. Clinical records and paraffin-embedded tumor specimens of 124 consecutive patients surgically treated for laryngeal (62 cases) and hypopharyngea