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Sample records for ameloblastic carcinoma based

  1. Treatment of ameloblastoma and ameloblastic carcinoma with radiotherapy.

    PubMed

    Kennedy, William R; Werning, John W; Kaye, Frederic J; Mendenhall, William M

    2016-10-01

    The purpose of this study is to report our institutional experience using radiotherapy in the treatment of ameloblastoma and ameloblastic carcinoma. Three patients with ameloblastoma and 3 patients with ameloblastic carcinoma were treated with radiotherapy alone (2 patients) or surgery and postoperative radiotherapy (4 patients) at the University of Florida between 1973 and 2007. Follow-up ranged from 4.0 to 13.1 years with a median of 7.8 years. Radiotherapy complications were scored using the Common Terminology Criteria for Adverse Events, version 4.0. Local control was achieved in 4 of the 6 patients. One patient treated with RT alone for an unresectable ameloblastoma developed a local recurrence and metastases in both the cervical lymph nodes and lungs, but had excellent response to dual BRAF/MEK inhibition with dabrafenib and trametinib. Another patient treated with surgery and postoperative radiotherapy for an ameloblastic carcinoma recurred locally without metastasis, but was not salvaged. No significant treatment-related complications were observed. For patients with local recurrence or inadequate margins after surgery, adjuvant radiotherapy provides the potential for disease control. In the setting of metastatic disease, targeted therapies may provide an additional opportunity for salvage. PMID:26796877

  2. Ameloblastic carcinoma (secondary type) with extensive squamous differentiation areas and dedifferentiated regions.

    PubMed

    Fonseca, Felipe Paiva; de Almeida, Oslei Paes; Vargas, Pablo Agustin; Gonçalves, Fábio; Corrêa Pontes, Flávia Sirotheau; Rebelo Pontes, Hélder Antônio

    2016-06-01

    Ameloblastic carcinoma is rare, accounting for 1.5%-2.0% of all odontogenic tumors. Few small series are available, but data on its clinicopathologic characteristics derive mainly from single case reports; therefore, descriptions of new cases may help to better understand the biological characteristics of this rare odontogenic malignancy. In the current report we describe an ameloblastic carcinoma affecting a 27-year-old female patient who had a previous diagnosis of ameloblastoma 7 years before. The carcinoma featured extensive areas of squamous differentiation resembling a primary intraosseous squamous cell carcinoma, as well as areas of dedifferentiation, a poorly documented histologic characteristic of ameloblastic carcinoma. This case provides new insights on the microscopic spectrum of ameloblastic carcinoma, permitting a critical discussion of the current World Health Organization classification of this odontogenic tumor. PMID:26768075

  3. Ameloblastic carcinoma of the maxilla: a report of two cases and a review of the literature.

    PubMed

    Fomete, Benjamin; Adebayo, Ezekiel Taiwo; Ayuba, Godwin Iko; Okeke, Uche Albert

    2016-02-01

    Ameloblastic carcinoma is a malignant form of ameloblastoma defined by histological evidence of malignancy in primary, recurrent, or metastatic tumor. Such a tumor is rare, and the maxilla is an unusual site. Due to its rarity, the characteristics of this tumor in the maxilla have not been well described. Case 1: A 55-year-old, ill-appearing Nigerian male presented to our center with left maxillary swelling of seven-year duration. The swelling had been slow-growing and painless until one year prior, when the growth became rapid and was coupled with severe pain. The swelling affected both oral function and facial esthetics, and the patient reported difficulty breathing. There was a maxillary, ulcerated swelling extending from teeth 12 to 18 and blocking the left nostril. The involved teeth were moderately mobile. Case 2: A 32-year-old male farmer presented with recurrent right maxillary swelling of six-year duration. Prior to this episode, he had undergone surgery for ameloblastoma (follicular type). The present swelling was fungating through the skin and protruding into the right nostril. Ameloblastic carcinoma is an aggressive odontogenic tumor that requires aggressive surgical treatment. PMID:26904494

  4. Ameloblastic carcinoma of the maxilla: a report of two cases and a review of the literature

    PubMed Central

    Adebayo, Ezekiel Taiwo; Ayuba, Godwin Iko; Okeke, Uche Albert

    2016-01-01

    Ameloblastic carcinoma is a malignant form of ameloblastoma defined by histological evidence of malignancy in primary, recurrent, or metastatic tumor. Such a tumor is rare, and the maxilla is an unusual site. Due to its rarity, the characteristics of this tumor in the maxilla have not been well described. Case 1: A 55-year-old, ill-appearing Nigerian male presented to our center with left maxillary swelling of seven-year duration. The swelling had been slow-growing and painless until one year prior, when the growth became rapid and was coupled with severe pain. The swelling affected both oral function and facial esthetics, and the patient reported difficulty breathing. There was a maxillary, ulcerated swelling extending from teeth 12 to 18 and blocking the left nostril. The involved teeth were moderately mobile. Case 2: A 32-year-old male farmer presented with recurrent right maxillary swelling of six-year duration. Prior to this episode, he had undergone surgery for ameloblastoma (follicular type). The present swelling was fungating through the skin and protruding into the right nostril. Ameloblastic carcinoma is an aggressive odontogenic tumor that requires aggressive surgical treatment. PMID:26904494

  5. Immunohistochemical Expression of GLUT-1 and HIF-1α in Tooth Germ, Ameloblastoma, and Ameloblastic Carcinoma.

    PubMed

    Sánchez-Romero, Celeste; Bologna-Molina, Ronell; Mosqueda-Taylor, Adalberto; Paes de Almeida, Oslei

    2016-08-01

    Hypoxia-inducible factor-1α (HIF-1α) promotes proteins that enable cell survival during hypoxia, such as glucose transporter 1 (GLUT-1). Their coexpression has been associated with aggressiveness in malignancies and has not been studied in odontogenic tumors. Immunohistochemical expression of HIF-1α and GLUT-1 was analyzed in 13 tooth germs (TGs), 55 ameloblastomas (AMs), and 3 ameloblastic carcinomas (ACs). HIF-1α was negative in all TGs, and just 1 case of AM and 1 of AC had nuclear positivity. GLUT-1 expressed in ameloblastic cells of all TGs, AMs, and ACs, with an increasing intensity, respectively, and was significantly higher in solid AM than in unicystic AM (P = .041). Absence of nuclear HIF-1α in TGs and most AMs suggest that GLUT-1 may be induced by alternative pathways to hypoxia. However, in ACs, HIF-1α may be activated; however, to confirm this, additional cases are needed. GLUT-1 overexpression could be related to aggressiveness in AMs and ACs and must represent a normal metabolite in TGs. PMID:27020375

  6. Evaluation of PKM2 and MAPK8IP2 Polymorphism in Ameloblastic Carcinoma: A Retrospective Quantitative Study

    PubMed Central

    Khodayari, Abbas; Ghaderian, Seyyed Mohammad Hossein; Jafarian, Mohammad; Jahangirnia, Alireza; Nayebi, Alireza; Akhlaghi, Fahimeh; Taghavi, Nasim; Akbarzadeh Najar, Reza; Tabarestani, Sanaz; Khojasteh, Arash; Aghabozorg Afjeh, Sarah

    2012-01-01

    Ameloblastic carcinoma (AC) is a rare malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Epidemiological evidence shows that human cancer is generally caused by genotoxic factors, genes involved in the susceptibility of cancer, including those involved in metabolism or detoxification of genotoxic environment and those controlling DNA replication. Nowadays, gene polymorphism has an important role in development of malignant tumor. We report a case series study of ameloblastic carcinoma and ameloblastoma to show the role of PKM2 and MAPK8IP2 polymorphisms in these tumors. The DNA was extracted separately from specimens in paraffin sections of the tumor. Polymorphism of these genes was determined by PCR-RFLP (Polymerase Chain Reaction-Restriction fragment length polymorphism) method. The allele distributions of all samples were in Hardy-Weinberg equilibrium. The genotype and allele distribution in these genes were not statistically different between patients and controls. PMID:24551779

  7. Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns.

    PubMed

    Carreón-Burciaga, Ramón Gil; González-González, Rogelio; Molina-Frechero, Nelly; Bologna-Molina, Ronell

    2015-01-01

    Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors. PMID:26823641

  8. Ameloblastic fibro-odontoma.

    PubMed

    Gantala, Ramlal; Gotoor, Srikanth Goud; Kumar, R Vijaya; Munisekhar, M S

    2015-06-04

    Ameloblastic fibro-odontoma is a slow growing, benign, expansile epithelial odontogenic tumour with odontogenic mesenchyme, accounting for 0.3-1.7% of jaw tumours, signifying its rarity. The WHO defines it as "a neoplasm composed of proliferating odontogenic epithelium in a cellular ectomesenchymal tissue with varying degrees of inductive changes and dental hard tissue formation". We report a case of an 11-year-old girl who presented to the Department of Maxillo-Facial Medicine and Radiology for the evaluation of a swelling in the left posterior mandible. Her clinical chart and investigations unveiled it as ameloblastic fibro-odontoma. After a promising presurgical evaluation, the lesion was enucleated using an intraoral approach followed by osteoplasty. Osteogenesis was attained despite of any definitive techniques to promote bone regeneration. Immediate postoperative inter-maxillary fixation was performed to prevent pathological fractures for a period of 3 weeks. In an 8-month follow-up, no untoward complications were noticed.

  9. Clinical and radiological profile of ameloblastic fibro-odontoma: an update on an uncommon odontogenic tumor based on a critical analysis of 114 cases.

    PubMed

    Buchner, Amos; Kaffe, Israel; Vered, Marilena

    2013-03-01

    Ameloblastic fibro-odontoma is an uncommon benign tumor of the jaws that belongs to the group of mixed odontogenic tumors. The descriptions of its clinical and radiological features in the literature are not always accurate and sometimes even contradictory. The aim of the present study was to critically evaluate their clinical and radiological features as reported in the English-language literature. A total of 114 well-documented cases of ameloblastic fibro-odontomas (103 from publications and 11 of our own new cases) were analyzed. The patients' age ranged from 8 months to 26 years (mean 9.6). There were 74 (65 %) males, with a male-to-female ratio of 1.85:1 (P = 0.001). The mandible was involved in 74 (65 %) cases, and the mandible-to-maxilla ratio was 1.85:1 (P < 0.001). Nearly 80 % of the lesions were located in the posterior region of the jaws, and most (58 %) were in the posterior mandible. Radiographically, most of the lesions were unilocular and only a few (~10 %) were multilocular. Most lesions were mixed radiolucent-radiopaque, and only a few (~5 %) were radiolucent. Almost all lesions (~92 %) were associated with the crown of an unerupted tooth/teeth. This comprehensive analysis of a large number of patients with an uncommon lesion revealed that ameloblastic fibro-odontomas are significantly more common in males and in the mandible, and that multilocular lesions are uncommon. It also revealed that, based on their clinical and radiological features, some of them are probably true neoplasms while others appear to be developing odontomas (hamartomas).

  10. Ameloblastic fibroma and its sarcomatous transformation.

    PubMed

    Prein, J; Remagen, W; Spiessl, B; Schafroth, U

    1979-12-01

    A case of ameloblastic fibroma, and one of its more aggressive variety, the ameloblastic "fibrosarcoma", are presented. The clinical and morphologic differences are discussed. In our opinion, ameloblastic "fibrosarcoma" is a semimalignant tumor. Therefore we propose "proliferating ameloblastic fibroma" as a more appropriate designation.

  11. Materials Engineering by Ameloblasts

    PubMed Central

    2015-01-01

    Enamel is unique. It is the only epithelial-derived mineralized tissue in mammals and has a distinct micro- and nanostructure with nanofibrous apatite crystals as building blocks. It is synthesized by a highly specialized cell, the ameloblast, which secretes matrix proteins with little homology to any other known amino acid sequence, but which is composed of a primary structure that makes it competent to self-assemble and control apatite crystal growth at the nanometer scale. The end-product of ameloblast activity is a marvel of structural engineering: a material optimized to provide the tooth with maximum biting force, withstanding millions of cycles of loads without catastrophic failure, while also protecting the dental pulp from bacterial attack. This review attempts to bring into context the mechanical behavior of enamel with the developmental process of amelogenesis and structural development, since they are linked to tissue function, and the importance of controlling calcium phosphate mineralization at the nanometer scale. The origins of apatite nanofibers, the development of a stiffness gradient, and the biological processes responsible for the synthesis of a hard and fracture-resistant dental tissue are discussed with reference to the evolution of enamel from a fibrous composite to a complex, tough, and damage-tolerant coating on dentin. PMID:25800708

  12. Materials engineering by ameloblasts.

    PubMed

    Habelitz, S

    2015-06-01

    Enamel is unique. It is the only epithelial-derived mineralized tissue in mammals and has a distinct micro- and nanostructure with nanofibrous apatite crystals as building blocks. It is synthesized by a highly specialized cell, the ameloblast, which secretes matrix proteins with little homology to any other known amino acid sequence, but which is composed of a primary structure that makes it competent to self-assemble and control apatite crystal growth at the nanometer scale. The end-product of ameloblast activity is a marvel of structural engineering: a material optimized to provide the tooth with maximum biting force, withstanding millions of cycles of loads without catastrophic failure, while also protecting the dental pulp from bacterial attack. This review attempts to bring into context the mechanical behavior of enamel with the developmental process of amelogenesis and structural development, since they are linked to tissue function, and the importance of controlling calcium phosphate mineralization at the nanometer scale. The origins of apatite nanofibers, the development of a stiffness gradient, and the biological processes responsible for the synthesis of a hard and fracture-resistant dental tissue are discussed with reference to the evolution of enamel from a fibrous composite to a complex, tough, and damage-tolerant coating on dentin. PMID:25800708

  13. Role of NBCe1 and AE2 in Secretory Ameloblasts

    PubMed Central

    Paine, Michael L.; Snead, Malcolm L.; Wang, HongJun; Abuladze, Natalia; Pushkin, Alexander; Liu, Weixin; Kao, Li Yo; Wall, Susan M.; Kim, Young-Hee; Kurtz, Ira

    2008-01-01

    The H+/base transport processes that control the pH of the microenvironment adjacent to ameloblasts are not currently well understood. Mice null for the AE2 anion exchanger have abnormal enamel. In addition, patients with mutations in the electrogenic sodium bicarbonate cotransporter NBCe1 and mice lacking NBCe1 have enamel abnormalities. These observations suggest that AE2 and NBCe1 play important roles in amelogenesis. The present study aimed to understand the roles of AE2 and NBC1 in ameloblasts. The data showed that NBCe1 is expressed at the basolateral membrane of secretory ameloblasts, whereas AE2 is expressed at the apical membrane. Transcripts for AE2a and NBCe1-B were detected in RNA isolated from cultured ameloblast-like LS8 cells. Our data are the first evidence that AE2 and NBCe1 are expressed in ameloblasts in vivo in a polarized fashion thereby providing a mechanism for ameloblast transcellular bicarbonate secretion in the process of enamel formation and maturation. PMID:18362326

  14. [The ameloblastic fibro-odontoma].

    PubMed

    Grätz, K W; Makek, M; Sailer, H F

    1991-01-01

    The ameloblastic fibro-odontoma is a rare nonagressive mixed odontogenic tumor. Most of these lesions occur in patients under 20 years. There is no sex predilection. They are located more often in the mandible, usually in the posterior segment. Painless swelling in the most common clinical sign. Radiologically, ameloblastic fibro-odontomas show a circumscribed radiolucency which contains radiopaque foci of various sizes and shapes. Histological examination reveals fibrous soft tissue and islands of odontogenic epithelium. The tumor produces enamel or enamel matrix, dentin and cementum. Treatment of ameloblastic fibro-odontomas usually consists of enucleation or surgical curettage. Eight cases of ameloblastic fibro-odontoma are reported and the clinical features, radiographic and histo-pathologic findings will be discussed along with the 67 cases found in the literature.

  15. Ameloblastic fibroma: an uncommon entity.

    PubMed

    Vij, Ruchieka; Vij, Hitesh

    2013-07-09

    Ameloblastic fibroma is an uncommon mixed odontogenic tumour, which is often confused with ameloblastoma. It exhibits both epithelial and mesenchymal components with absence of any calcified dental structure. This paper presents two cases of this rare entity with detailed review of literature.

  16. Molecular and circadian controls of ameloblasts

    PubMed Central

    Athanassiou-Papaefthymiou, Maria; Kim, Doohak; Harbon, Lindsay; Papagerakis, Silvana; Schnell, Santiago; Harada, Hidemitsu; Papagerakis, Petros

    2012-01-01

    Stage-specific expression of ameloblast-specific genes is controlled by differential expression of transcription factors. In addition, ameloblasts follow daily rhythms in their main activities i.e. enamel protein secretion and enamel mineralization. This time related control is orchestrated by oscillations of clock proteins involved in circadian rhythms regulation. Our aim was to identify the potential links between daily rhythms and developmental controls of ameloblast differentiation. The effects of selected transcriptional factors Distal-less homeobox 3 (Dlx3) and Runt related transcription factor 2 (Runx2) and clock gene Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) on secretory and maturation ameloblasts [using stage-specific markers amelogenin (Amel), enamelin (Enam) and kallikrein related-peptidase 4 (Klk4)] were evaluated in HAT-7 ameloblast cell line. Amel and Enam steady-state RNA expression levels were down-regulated in Runx2 over-expressing cells and up-regulated in Dlx3 over-expressing cells. In contrast, Klk4 was up-regulated by both Dlx3 and Runx2. Furthermore, a temporal and spatial relationship between clock genes and ameloblast differentiation markers was detected. Of interest, clock genes not only affected rhythmic expression of ameloblast specific genes but also influenced the expression of Runx2. Multi-scale mathematical modeling is being explored to further understand the temporal and developmental controls of ameloblast differentiation. Our study provides novel insights into the regulatory mechanisms sustaining ameloblast differentiation. PMID:22243224

  17. Ameloblastic fibromas and related tumors in cattle.

    PubMed

    Gardner, D G

    1996-03-01

    This article concerns rare odontogenic tumors that occur predominantly in the mandibular incisor region of young cattle and which have often in the past been referred to as ameloblastomas, or as the outdated synonym, adamantinoma. Twenty-two examples from the literature and two new ones were studied. Six consisted of epithelial islands which resembled those of ameloblastoma but which were located within a cellular fibrous connective tissue that was the second component of the tumor; these mixed odontogenic tumors therefore represented ameloblastic fibromas, not ameloblastomas. Eight consisted of a combination of ameloblastic fibroma and odontoma and therefore were ameloblastic fibro-odontomas, and one was apparently malignant (ameloblastic fibro-odontosarcoma). Excluding this last lesion, these tumors should respond well to enucleation, like their human counterparts but, to confirm this hypothesis, the margins of future examples should be carefully examined to determine that they are well-demarcated, not invasive. The microscopic features of the remaining 9 tumours could not be evaluated adequately, while another 17 tumors in cattle and water buffalo reported briefly could not be studied to any extent because of insufficient information.

  18. Ameloblastic fibroma and related lesions: current pathologic concept.

    PubMed

    Takeda, Y

    1999-11-01

    Ameloblastic fibroma (AF) is a true mixed tumor, in which the epithelial and the ectomesenchymal elements are neoplastic. There are two rare variants of AF; granular cell AF and peripheral AF. Ameloblastic fibrosarcoma is a rare tumor, and is regarded as the malignant counterpart of the benign AF. Recent immunohistochemical study using MIB-1 shows labelling indices in the mesenchymal component of the recurrent AF and ameloblastic fibrosarcoma are quite high, in contrast with the conventional AF. Ameloblastic fibrodentinoma is a histologic variant of AF in which dentin or dentinoid tissue has formed, but there is no eveidence that ameloblastic fibrodentinoma exhibit a different biologic behavior than ordinary AF. Ameloblastic fibro-odontoma is a lesion similar to AF, but also showing inductive changes that lead to the formation of both dentin and enamel. Some lesions diagnosed as ameloblastic fibro-odontoma are probably developing odontoma, but the others should not be considered as hamartomatous in nature, since there are rare cases of ameloblastic fibro-odontoma showing true neoplastic behavior, and since the existence of malignant variant is evident. In revised WHO's classification of odontogenic tumors, the terms "ameloblastic fibrodentinoma" and "dentinoma" are used synonymously, however, there are histologic difference between several cases reported previously as "dentinoma" and ameloblastic fibrodentinoma.

  19. The Impact of Fluoride on Ameloblasts and the Mechanisms of Enamel Fluorosis

    PubMed Central

    Bronckers, A.L.J.J.; Lyaruu, D.M.; DenBesten, P.K.

    2009-01-01

    Intake of excess amounts of fluoride during tooth development cause enamel fluorosis, a developmental disturbance that makes enamel more porous. In mild fluorosis, there are white opaque striations across the enamel surface, whereas in more severe cases, the porous regions increase in size, with enamel pitting, and secondary discoloration of the enamel surface. The effects of fluoride on enamel formation suggest that fluoride affects the enamel-forming cells, the ameloblasts. Studies investigating the effects of fluoride on ameloblasts and the mechanisms of fluorosis are based on in vitro cultures as well as animal models. The use of these model systems requires a biologically relevant fluoride dose, and must be carefully interpreted in relation to human tooth formation. Based on these studies, we propose that fluoride can directly affect the ameloblasts, particularly at high fluoride levels, while at lower fluoride levels, the ameloblasts may respond to local effects of fluoride on the mineralizing matrix. A new working model is presented, focused on the assumption that fluoride increases the rate of mineral formation, resulting in a greater release of protons into the forming enamel matrix. PMID:19783795

  20. Extensive Mandibular Ameloblastic Fibro-Odontoma.

    PubMed

    Ribeiro, Cínthia Magalhães; Santos, Tatiana Tavares Marcelino Dos; de Castro, Sérgio Roberto; de Carli, Marina Lara; Sperandio, Felipe Fornias; Hanemann, João Adolfo Costa; Pereira, Alessandro Antônio Costa

    2016-09-01

    Ameloblastic fibro-odontoma (AFO) is a mixed odontogenic tumor that presents epithelial and mesenchymal components. Ameloblastic fibro-odontoma is generally diagnosed between the first and second decades of life and normally shows a slow clinical growth in the posterior portion of the maxilla or mandible, being mostly associated with 1 or more impacted teeth. Radiographic features of AFO show a radiolucent well-defined, uni, or multilocular defect due to containing variable amounts of calcified material. The enucleation of the tumor is the usual conduct and should be followed up for a long period of time. Here, the authors report the case of 17-year-old male patient who presented an extensive AFO on the right posterior side of the mandible. The panoramic radiograph and the tomographic examination revealed a multilocular radiolucent lesion with impacted teeth. Histological examination revealed connective tissue resembling the dental papilla along with epithelial strands or islands, as well as dental hard tissue such enamel and dentin. Enucleation and curettage was performed and led to good outcome. There was no recurrence after an 8-year follow-up, and oral rehabilitation was performed with dental implants.

  1. Ameloblastic Fibrodentinoma: Report of a Case in an Infant

    PubMed Central

    Bhargava, Manish; Rathore, Pallvi

    2016-01-01

    Ameloblastic fibrodentinoma (AFD) is a debatable neoplasm with respect to its clinical, biological and histopathological diagnosis. The clinical and radiological presentation may mimic ameloblastic fibro odontoma, odontoma, ameloblastic fibroma and cemento-ossifying fibroma. We report an interesting case of AFD occurring in canine region of mandible in a one-year-old infant. From a review of English language literature, to the best of our knowledge this is the first case occurring in an infant. The purpose of this case report is to create awareness among the clinicians to make the best possible management of this controversial pathologic entity. PMID:26894185

  2. Ameloblastic Fibrodentinoma: Report of a Case in an Infant.

    PubMed

    Bhargava, Manish; Sood, Saloni; Rathore, Pallvi

    2016-01-01

    Ameloblastic fibrodentinoma (AFD) is a debatable neoplasm with respect to its clinical, biological and histopathological diagnosis. The clinical and radiological presentation may mimic ameloblastic fibro odontoma, odontoma, ameloblastic fibroma and cemento-ossifying fibroma. We report an interesting case of AFD occurring in canine region of mandible in a one-year-old infant. From a review of English language literature, to the best of our knowledge this is the first case occurring in an infant. The purpose of this case report is to create awareness among the clinicians to make the best possible management of this controversial pathologic entity.

  3. Ameloblastic Fibrodentinoma: Report of a Case in an Infant.

    PubMed

    Bhargava, Manish; Sood, Saloni; Rathore, Pallvi

    2016-01-01

    Ameloblastic fibrodentinoma (AFD) is a debatable neoplasm with respect to its clinical, biological and histopathological diagnosis. The clinical and radiological presentation may mimic ameloblastic fibro odontoma, odontoma, ameloblastic fibroma and cemento-ossifying fibroma. We report an interesting case of AFD occurring in canine region of mandible in a one-year-old infant. From a review of English language literature, to the best of our knowledge this is the first case occurring in an infant. The purpose of this case report is to create awareness among the clinicians to make the best possible management of this controversial pathologic entity. PMID:26894185

  4. Ameloblastic fibro-odontoma: a case report.

    PubMed

    Cavalcante, Ana-Sueli-Rodrigues; Anbinder, Ana-Lia; Costa, Nívea-Cristina-Sena; Lima, José-Roberto Sá; Carvalho, Yasmin-Rodarte

    2009-12-01

    Ameloblastic fibro-odontoma (AFO) is a rare, benign, slow-growing odontogenic tumor, generally asymptomatic and more prevalent in children and adolescents. We report a case of AFO in the mandible of an eight-year-old Caucasian male patient, and review the literature . Intraoral examination revealed a swelling extending from the deciduous second molar to the retromolar triangle, covered with normal mucosa. A panoramic radiograph showed a large, well-demarcated radiolucency with radiopaque areas. The provisional diagnosis was of AFO, and so an incisional biopsy was performed. Histologically, the lesion was composed of connective tissue resembling the dental papilla, with epithelial strands or islands, as well as denticles and amorphous masses of enamel and dentin consistent with a diagnosis of AFO. Surgical excision and curettage of the lesion were performed. The patient has been monitored for eight years and the lesion has not recurred.

  5. Ameloblastic Fibrosarcoma Arising in the Maxilla

    PubMed Central

    Pillay, Rachael R.; Bilski, Arthur; Batstone, Martin

    2016-01-01

    Background: Ameloblastic fibrosarcoma (AFS) is a rare odontogenic neoplasm of the jaw that usually arises de novo or through a malignant change in the mesenchymal component of a preexisting or recurrent benign fibroma. The majority of AFS cases reported in the literature arise in the mandible. Case Report: A 35-year-old male presented with an asymptomatic left maxillary mass that on imaging was found to be effacing most of his maxillary sinus. He underwent a left maxillectomy with free-flap reconstruction and adjuvant radiotherapy to the tumor bed. Conclusion: Wide local excision remains the treatment of choice for AFS, given the poor survival rates of patients with recurrent disease. However, long-term studies and follow-up are needed to elucidate the role of adjuvant therapies in the primary treatment of AFS. PMID:27303223

  6. Pigmented ameloblastic fibro-odontoma: clinical, histological, and immunohistochemical profile.

    PubMed

    Martínez Martínez, Marisol; Romero, Celeste Sánchez; Piña, Alicia Rumayor; Palma Guzmán, José Mario; de Almeida, Oslei Paes

    2015-02-01

    Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy.

  7. Ameloblastic fibro-odontoma in children: report of 2 cases.

    PubMed

    Santos, Thiago de Santana; de Carvalho, Ricardo Wathson Feitosa; Avelar, Rafael Linard; Dias de Oliveira e Silva, Emanuel; Frota, Riedel; Anjos, Edvaldo Dória

    2011-01-01

    Ameloblastic fibro-odontoma is a rare, mixed, benign, odontogenic tumor of significant prevalence in the mandible, with epithelial and mesenchymal components. It usually affects pediatric patients and is associated with teeth, causing a delay in eruption chronology or an alteration in the dental eruption pathway. It is occasionally diagnosed during radiographic evaluations of these patients. The literature is unclear whether it is a distinct pathological entity or a stage of odontoma. As it is benign and has a low recurrence rate, conservative treatment is recommended. The purpose of this paper was to present 2 cases of ameloblastic fibro-odontoma in the mandibles of children.

  8. Epithelial Dysplasia in Ameloblastic Fibrosarcoma Arising from Recurrent Ameloblastic Fibroma in a 26-Year-Old Iranian Man

    PubMed Central

    Mohsenifar, Zhaleh; Behrad, Samira; Abbas, Fatemeh Mashhadi

    2015-01-01

    Patient: Male, 26 Final Diagnosis: Ameloblastic fibrosarcoma Symptoms: Swelling Medication: — Clinical Procedure: Hemimandibulectomy Specialty: Dentistry Objective: Rare disease Background: Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor with a mesenchymal component, showing sarcomatous features and epithelial nests resembling ameloblastic fibroma (AF). Case Report: We report a case of AFS showing epithelial dysplasia arising in a recurrent AF in the left mandible after 3 years in a 26-year-old man, which is regarded as an uncommon histopathologic finding in AFS. We also emphasize the comprehensive clinical, radiographic, and histopathologic evaluation, and immunohistochemical staining of this patient. Conclusions: We conclude that it is important to consider malignancy alternations in the epithelial component of AFS, along with that of the mesenchymal component, to provide a proper diagnosis and treatment of recurrent AF. PMID:26289384

  9. Ameloblastic Fibrosarcoma of the mandible evolving from a prior Ameloblastic Fibroma after two years: an unusual finding.

    PubMed

    Bertoni, Franco; Del Corso, Giacomo; Bacchini, Patrizia; Marchetti, Claudio; Tarsitano, Achille

    2016-10-01

    Transformation of an ameloblastic fibroma to an ameloblastic fibrosarcoma has been reported rarely in the literature. The present case report describes such evolution in a patient under long-term follow-up. The patient was first treated in 2008, and he developed the malignant counterpart of the disease 2 years later. The patient is currently under careful long-term follow-up and is free of disease. This article describes the clinical and radiographic features, histological characteristics, immunohistochemical findings, and surgical treatment of the tumor.

  10. [Mixed odontogenic tumors. Studies on the significance of correlations between ameloblastic fibroma, ameloblastic fibro-odontoma and odontoma].

    PubMed

    Fabris, G A; Ferretti, S; Balderi, A; Trombelli, L; Calura, G

    1991-03-01

    The purpose of the present study was to evaluate the interrelationship between the mixed odontogenic tumors. A population of 292 cases--9 cases from our own files, 283 cases taken from the literature--was considered. Data concerning age, sex distribution and site of occurrence of the different lesions were statistically analyzed. The results showed a significant prevalence of odontomas in the anterior region and a highly significant correlation for age and site distribution in relation to the various lesions. It is supposed that ameloblastic fibroma, ameloblastic fibro-odontoma and odontoma represent different maturational stages of the same lesion whose histogenesis is linked to the odontogenic process.

  11. MSX2 in ameloblast cell fate and activity

    PubMed Central

    Babajko, Sylvie; de La Dure-Molla, Muriel; Jedeon, Katia; Berdal, Ariane

    2015-01-01

    While many effectors have been identified in enamel matrix and cells via genetic studies, physiological networks underlying their expression levels and thus the natural spectrum of enamel thickness and degree of mineralization are now just emerging. Several transcription factors are candidates for enamel gene expression regulation and thus the control of enamel quality. Some of these factors, such as MSX2, are mainly confined to the dental epithelium. MSX2 homeoprotein controls several stages of the ameloblast life cycle. This chapter introduces MSX2 and its target genes in the ameloblast and provides an overview of knowledge regarding its effects in vivo in transgenic mouse models. Currently available in vitro data on the role of MSX2 as a transcription factor and its links to other players in ameloblast gene regulation are considered. MSX2 modulations are relevant to the interplay between developmental, hormonal and environmental pathways and in vivo investigations, notably in the rodent incisor, have provided insight into dental physiology. Indeed, in vivo models are particularly promising for investigating enamel formation and MSX2 function in ameloblast cell fate. MSX2 may be central to the temporal-spatial restriction of enamel protein production by the dental epithelium and thus regulation of enamel quality (thickness and mineralization level) under physiological and pathological conditions. Studies on MSX2 show that amelogenesis is not an isolated process but is part of the more general physiology of coordinated dental-bone complex growth. PMID:25601840

  12. A peripheral ameloblastic fibro-odontoma in a 3-year-old girl: case report, immunohistochemical analysis, and literature review.

    PubMed

    Lin, Yi-Chun; Hsu, Hsiu-Ming; Liu, Chiang-Shin; Yuan, Kuo

    2014-01-01

    Ameloblastic fibro-odontoma (AFO) predominantly occurs in the jaw bones of children and young adults. Extraosseous AFO is extremely rare. We describe a peripheral ameloblastic fibro-odontoma in the maxillary gingiva of a 3-year-old girl. The clinical appearance resembled fiery red reactive gingival lesions. The histopathological examination of the excised lesion showed small islands and cords of odontogenic epithelium with cellular myxoid stroma in the subepithelial tissue. The mass contained calcified material and an enamel-like deposit. Many small blood vessels appeared in the connective tissue surrounding the odontogenic epithelium. The immunohistochemical assays showed strong reactivity for amelogenin, β-catenin, CD44, and CD31 in the tissue sections. There was no recurrence after the 1-year follow-up. Because this lesion clinically resembles other nonneoplastic lesions and is very rare in gingiva, establishing a correct diagnosis is achieved only based on specific histological characteristics. Conservative excision of the tumor is the treatment of choice.

  13. Calcifying odontogenic cyst with ameloblastic fibroma: report of three cases.

    PubMed

    Lin, Cheng-Chung; Chen, Chung-Ho; Lin, Li-Min; Chen, Yuk-Kwan; Wright, John M; Kessler, Harvey P; Cheng, Yi-Shing Lisa; Ellis, Edward

    2004-10-01

    Although it is a rare event, odontogenic tumors such as ameloblastoma, ameloblastic fibroma (AF), ameloblastic fibro-odontoma, and odontoma have been reported associated with calcifying odontogenic cyst (COC). There are only four cases of COC with AF cited in the English literature. However, three of these four cases were either included in a review of a series of cases or reported as an abstract, and limited clinical and histological information was provided. We present three additional cases of COC with AF and discuss the management for this combined lesion. Because COC is known for its histologic diversity and variable clinical behavior, and the clinical significance of an association of COC with AF is still unknown, we think it is valuable to report COC with AF with detailed clinical and pathological documentation.

  14. The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells.

    PubMed

    Zheng, Li-Wei; Linthicum, Logan; DenBesten, Pamela K; Zhang, Yan

    2013-03-01

    This study aimed to compare epithelial cells derived from human embryonic stem cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine their potential use as a cell source for ameloblast regeneration. Induced by various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA) and lithium chloride (LiCl) for 7 days, hESCs adopted cobble-stone epithelial phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14. Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs. ES-ECs were compared with human fetal skin epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well. ALCs had relatively high expression levels of cytokeratin 76, which was also found to be upregulated in ES-ECs. Based on the present study, with the similarity of gene expression with ALCs, ES-ECs are a promising potential cell source for regeneration, which are not available in erupted human teeth for regeneration of enamel.

  15. High-fluoride promoted phagocytosis-induced apoptosis in a matured ameloblast-like cell line.

    PubMed

    Yang, Ting; Zhang, Yanli; Zheng, Dongdong; Hao, Ying; Snead, Malcolm L; Duan, Xiaohong

    2015-01-01

    Endocytosis and phagocytosis are important physiologic activities occurring during ameloblast differentiation. We have previously found that excess fluoride inhibited ameloblasts endocytotic functions. Here, we hypothesized that increasing amounts of fluoride may affect ameloblast phagocytotic function during their differentiation. Using cell culture, we first induced maturation of the mouse ameloblast-like LS8 cells by treatment with exogenous retinoic acid (RA) and dexamethasone (DEX). We measured their phagocytotic activity by fluorescent microscopy using a live cell visualization station. We found that ameloblast-like LS8 cells matured with RA/DEX treatment and the increasing amounts of fluoride demonstrated the up-regulated expression of the phagocytotic marker proteins, LAMP1 and CD68. A connection between phagocytosis and apoptosis was confirmed by the increased number of phagocytotic vacuole-like structures and the heterochromatin margination phenomenon observed in the RA/DEX with NaF treatment group. The increase in albumin uptake by ameloblasts was confirmed using whole organ culture of incisor tooth germs. Here, in fluoride treated tooth germs, mature canonical ameloblasts showed greater amounts of albumin uptake, which was accompanied by decreased expression of the anti-apoptosis marker, Bcl-2 along with up-regulated expression of CD68. From these observations, we inferred that high doses of fluoride may cause apoptosis by increasing the phagocytosis of protein particles in mature-stage ameloblasts and loss of Bcl-2 signals might be involved in this process.

  16. Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity.

    PubMed

    Zhang, Yan; Kim, Ji-Yeon; Horst, Orapin; Nakano, Yukiko; Zhu, Li; Radlanski, Ralf J; Ho, Sunita; Den Besten, Pamela K

    2014-01-01

    Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of 4.5 µM, a four-fold increase over control mice with no fluoride added to drinking water. MicroCT analyses showed delayed and incomplete mineralization of fluorosed incisor enamel as compared to control enamel. A microarray analysis of secretory and maturation stage ameloblasts microdissected from control and fluorosed mouse incisors showed that genes clustered with Mmp20 appeared to be less downregulated in maturation stage ameloblasts of fluorosed incisors as compared to control maturation ameloblasts. One of these Mmp20 co-regulated genes was the global chromatin organizer, special AT-rich sequence-binding protein-1 (SATB1). Immunohistochemical analysis showed increased SATB1 protein present in fluorosed ameloblasts compared to controls. In vitro, exposure of human ameloblast-lineage cells to micromolar levels of both NaF and AlF3 led to a significantly increase in SATB1 protein content, but not levels of Satb1 mRNA, suggesting a fluoride-induced mechanism protecting SABT1 from degradation. Consistent with this possibility, we used immunohistochemistry and Western blot to show that fluoride exposed ameloblasts had increased phosphorylated PKCα both in vivo and in vitro. This kinase is known to phosphorylate SATB1, and phosphorylation is known to protect SATB1 from degradation by caspase-6. In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts.

  17. Fluorosed Mouse Ameloblasts Have Increased SATB1 Retention and Gαq Activity

    PubMed Central

    Zhang, Yan; Kim, Ji-Yeon; Horst, Orapin; Nakano, Yukiko; Zhu, Li; Radlanski, Ralf J.; Ho, Sunita; Besten, Pamela K. Den

    2014-01-01

    Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of 4.5 µM, a four-fold increase over control mice with no fluoride added to drinking water. MicroCT analyses showed delayed and incomplete mineralization of fluorosed incisor enamel as compared to control enamel. A microarray analysis of secretory and maturation stage ameloblasts microdissected from control and fluorosed mouse incisors showed that genes clustered with Mmp20 appeared to be less downregulated in maturation stage ameloblasts of fluorosed incisors as compared to control maturation ameloblasts. One of these Mmp20 co-regulated genes was the global chromatin organizer, special AT-rich sequence-binding protein-1 (SATB1). Immunohistochemical analysis showed increased SATB1 protein present in fluorosed ameloblasts compared to controls. In vitro, exposure of human ameloblast-lineage cells to micromolar levels of both NaF and AlF3 led to a significantly increase in SATB1 protein content, but not levels of Satb1 mRNA, suggesting a fluoride-induced mechanism protecting SABT1 from degradation. Consistent with this possibility, we used immunohistochemistry and Western blot to show that fluoride exposed ameloblasts had increased phosphorylated PKCα both in vivo and in vitro. This kinase is known to phosphorylate SATB1, and phosphorylation is known to protect SATB1 from degradation by caspase-6. In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts. PMID:25090413

  18. Hepatocellular carcinoma and evidence-based surgery

    PubMed Central

    Braillon, Alain

    2009-01-01

    Transplantation cannot be considered the most important therapeutic procedure for hepatocellular carcinoma (HCC). In France, no more than 2% of patients with HCC undergo a transplantation. Randomized controlled trial must assess the benefit to risk ratio of various potentially “curative” treatment procedures (transplantation, resection, radio-frequency ablation). PMID:19908350

  19. Large ameloblastic fibro-odontoma in an 18-year-old girl and review of literature.

    PubMed

    Pillai, Ajay; Moghe, Swapnil; Guru, Kanishka Navin; Nair, Preeti P

    2012-11-19

    The ameloblastic fibro-odontoma is a rare, benign, mixed neoplasm composed of proliferating odontogenic epithelium, ectomesenchymal tissue and varying degrees of dental hard tissue formation. It occurs exclusively as an intraosseous lesion. It usually exhibits slow growth and is commonly seen in children and young adults. Radiologically, ameloblastic fibro-odontoma appears as a circumscribed radiolucency which may contain radiopaque foci. Most cases of ameloblastic fibro-odontoma exhibit benign behaviour, but cases of malignant transformation have been reported. The treatment modality in most cases involves conservative surgery, but in cases with malignant transformation more radical treatment will be required. A massive ameloblastic fibro-odontoma involving the mandible is being described here with its clinical, radiological and histopathological features.

  20. [Ameloblastic fibro-odontoma. Clinical aspects and review of the literature].

    PubMed

    Villareal, P M; Junquera, L M; Albertos, J M; Molina, R; Gonzalez, S; Villarreal, P M

    1998-02-01

    Ameloblastic fibro-odontoma is a rare odontogenic tumor. It is formed by proliferation of epithelial odontogenic elements combined with ectomesechimal tissue. The presence of dentine, enamel and osteoid like tissue can be identified. Cases of sarcomatous degeneration have been described. In this work, we present two new cases of ameloblastic fibro-odontoma, analyzing the most important aspects of their differential diagnosis, with a review of literature.

  1. Function and repair of dental enamel - Potential role of epithelial transport processes of ameloblasts.

    PubMed

    Varga, Gábor; Kerémi, Beáta; Bori, Erzsébet; Földes, Anna

    2015-07-01

    The hardest mammalian tissue, dental enamel is produced by ameloblasts, which are electrolyte-transporting epithelial cells. Although the end product is very different, they show many similarities to transporting epithelia of the pancreas, salivary glands and kidney. Enamel is produced in a multi-step epithelial secretory process that features biomineralization which is an interplay of secreted ameloblast specific proteins and the time-specific transport of minerals, protons and bicarbonate. First, "secretory" ameloblasts form the entire thickness of the enamel layer, but with low mineral content. Then they differentiate into "maturation" ameloblasts, which remove organic matrix from the enamel and in turn further build up hydroxyapatite crystals. The protons generated by hydroxyapatite formation need to be buffered, otherwise enamel will not attain full mineralization. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. The whole process has been the focus of many immunohistochemical and gene knock-out studies, but, perhaps surprisingly, no functional data existed for mineral ion transport by ameloblasts. However, recent studies including ours provided a better insight for molecular mechanism of mineral formation. The secretory regulation is not completely known as yet, but its significance is crucial. Impairing regulation retards or prevents completion of enamel mineralization and results in the development of hypomineralized enamel that easily erodes after dental eruption. Factors that impair this function are fluoride and disruption of pH regulators. Revealing these factors may eventually lead to the treatment of enamel hypomineralization related to genetic or environmentally induced malformation.

  2. Ameloblasts require active RhoA to generate normal dental enamel.

    PubMed

    Xue, Hui; Li, Yong; Everett, Eric T; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M; Kuehl, Melissa A; Pugach, Megan K; Bouchard, Jessica; Gibson, Carolyn W

    2013-08-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo dramatic cytoskeletal changes and the RhoA protein level is up-regulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene-regulatory sequences. Transgenic and wild-type (WT) molar tooth germs were incubated with sodium fluoride (NaF) or sodium chloride (NaCl) in organ culture. Filamentous actin (F-actin) stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared with WT ameloblasts treated with NaCl or with transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/Rho-associated protein kinase (ROCK) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between WT and transgenic incisors from mice provided with drinking water containing NaF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin, E-cadherin, and Ki67 compared with WT molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited.

  3. Establishment of primary cultures for mouse ameloblasts as a model of their lifetime

    SciTech Connect

    Suzawa, Tetsuo . E-mail: suzawa@dent.showa-u.ac.jp; Itoh, Nao; Takahashi, Naoyuki; Katagiri, Takenobu; Morimura, Naoko; Kobayashi, Yasuna; Yamamoto, Toshinori; Kamijo, Ryutaro

    2006-07-07

    To understand how the properties of ameloblasts are spatiotemporally regulated during amelogenesis, two primary cultures of ameloblasts in different stages of differentiation were established from mouse enamel epithelium. Mouse primary ameloblasts (MPAs) prepared from immature enamel epithelium (MPA-I) could proliferate, whereas those from mature enamel epithelium (MPA-M) could not. MPA-M but not MPA-I caused apoptosis during culture. The mRNA expression of amelogenin, a marker of immature ameloblasts, was down-regulated, and that of enamel matrix serine proteiase-1, a marker of mature ameloblasts, was induced in MPA-I during culture. Using green fluorescence protein as a reporter, a visualized reporter system was established to analyze the promoter activity of the amelogenin gene. The region between -1102 bp and -261 bp was required for the reporter expression in MPA-I. These results suggest that MPAs are valuable in vitro models for investigation of ameloblast biology, and that the visualized system is useful for promoter analysis in MPAs.

  4. Ameloblasts require active RhoA to generate normal dental enamel

    PubMed Central

    Li, Yong; Xue, Hui; Everett, Eric T.; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M.; Kuehl, Melissa A.; Pugach, Megan K.; Bouchard, Jessica; Gibson, Carolyn W.

    2013-01-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment and cell proliferation. During amelogenesis, ameloblasts which produce the enamel proteins undergo dramatic cytoskeletal changes and RhoA protein level is upregulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene regulatory sequences. Transgenic and WT molar tooth germs were incubated with NaF or NaCl in organ culture. F-actin stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared to WT ameloblasts treated with NaCl or compared to transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/ROCK pathway in the transgenic mice. Little difference in quantitative fluorescence (estimation of fluorosis) was observed between WT and transgenic incisors from mice provided NaF in their drinking water. We subsequently found reduced transgene expression in incisors compared to molars. Transgenic molar teeth had reduced amelogenin, E-cadherin and Ki67 compared to WT. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited. PMID:23841780

  5. Ctip2/Bcl11b controls ameloblast formation during mammalian odontogenesis.

    PubMed

    Golonzhka, Olga; Metzger, Daniel; Bornert, Jean-Marc; Bay, Brian K; Gross, Michael K; Kioussi, Chrissa; Leid, Mark

    2009-03-17

    The transcription factor Ctip2/Bcl11b plays essential roles in developmental processes of the immune and central nervous systems and skin. Here we show that Ctip2 also plays a key role in tooth development. Ctip2 is highly expressed in the ectodermal components of the developing tooth, including inner and outer enamel epithelia, stellate reticulum, stratum intermedium, and the ameloblast cell lineage. In Ctip2(-/-) mice, tooth morphogenesis appeared to proceed normally through the cap stage but developed multiple defects at the bell stage. Mutant incisors and molars were reduced in size and exhibited hypoplasticity of the stellate reticulum. An ameloblast-like cell population developed ectopically on the lingual aspect of mutant lower incisors, and the morphology, polarization, and adhesion properties of ameloblasts on the labial side of these teeth were severely disrupted. Perturbations of gene expression were also observed in the mandible of Ctip2(-/-) mice: expression of the ameloblast markers amelogenin, ameloblastin, and enamelin was down-regulated, as was expression of Msx2 and epiprofin, transcription factors implicated in the tooth development and ameloblast differentiation. These results suggest that Ctip2 functions as a critical regulator of epithelial cell fate and differentiation during tooth morphogenesis.

  6. Dental enamel structure is altered by expression of dominant negative RhoA in ameloblasts.

    PubMed

    Li, Yong; Pugach, Megan K; Kuehl, Melissa A; Peng, Li; Bouchard, Jessica; Hwang, Soon Y; Gibson, Carolyn W

    2011-01-01

    Using in vitrotooth germ cultures and analysis by confocal microscopy, ameloblasts treated with sodium fluoride were found to have elevated amounts of filamentous actin. Because this response is reduced by inhibitors of the Rho/ROCK signaling pathway, we generated mice that express dominant negative RhoA (RhoA(DN)) in ameloblasts for in vivo analysis. Expression of the EGFP-RhoA(DN) fusion protein was evaluated by RT-PCR and immunohistochemistry, and teeth were analyzed by scanning electron microscopy. The 3 strains expressed at either low (TgEGFP-RhoA(DN)-8), intermediate (TgEGFP-RhoA(DN)-2), or high (TgEGFP-RhoA(DN)-13) levels, and the molar teeth from the 3 strains had enamel hypoplasia and surface defects. We conclude that RhoA(DN) expressed in ameloblasts interferes with normal enamel development through the pathway that is induced by sodium fluoride.

  7. Ameloblastic fibro-odontoma. Case report and review of the literature.

    PubMed

    De Riu, Giacomo; Meloni, Silvio Mario; Contini, Marcella; Tullio, Antonio

    2010-03-01

    Ameloblastic fibro-odontoma (AFO) is defined by the World Health Organization (WHO) as a neoplasm composed of proliferating odontogenic epithelium. It is a benign, slow-growing, expansive tumour that clinically appears as a well-encapsulated, benign lesion. Histologically, AFO has been classified as an ameloblastic fibroma or odontoma. Despite numerous efforts, however, there is still considerable confusion concerning the nature, the histology and the therapy of these lesions. This paper reports an additional case of a large AFO and reviews the relevant literature regarding the clinical and pathologic features of this lesion.

  8. Calcifying cystic odontogenic tumor associated with ameloblastic fibro-odontoma of the anterior mandible.

    PubMed

    Lee, Jun; Song, Young-Gook; Moon, Seong-Yong; Choi, Boyoung; Kim, Bong Chul; Yoon, Jung-Hoon

    2014-05-01

    Calcifying cystic odontogenic tumor, which was formerly named calcifying odontogenic cyst, is a benign odontogenic tumor containing clusters of ghost cells within ameloblastic epithelium. Calcifying cystic odontogenic tumors have been associated with other odontogenic tumors, a finding that is a rare event in other types of odontogenic cysts or tumors. This report describes a case of hybrid odontogenic tumor composed of calcifying cystic odontogenic tumor and ameloblastic fibroma-odontoma of the anterior mandible that occurred in a 4-year-old Korean girl.

  9. Monitoring the progression from intraductal carcinoma to invasive ductal carcinoma based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-09-01

    Intraductal carcinoma is a precancerous lesion of the breast and the immediate precursor of invasive ductal carcinoma. Multiphoton microscopy (MPM) was used to monitor the progression from intraductal carcinoma to invasive ductal carcinoma, which can improve early detection of precursor lesions and halt progression to invasive neoplastic disease. It was found that MPM has the capability to reveal the qualitative changes in features of cells, structure of basement membranes, and architecture of collagens during the development from intraductal carcinoma to invasive ductal carcinoma, as well as the quantitative alterations in nuclear area, circle length of basement membrane, and collagen density. Combined with intra-fiberoptic ductoscopy or transdermal biopsy needle, MPM has the potential to provide immediate histological diagnosis of tumor progression in the field of breast carcinoma.

  10. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case.

    PubMed

    Atarbashi Moghadam, Saede; Mokhtari, Sepideh

    2016-01-01

    Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment.

  11. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case

    PubMed Central

    Atarbashi Moghadam, Saede

    2016-01-01

    Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment. PMID:26981293

  12. {beta}-Catenin/LEF1 activated enamelin expression in ameloblast-like cells

    SciTech Connect

    Tian, Hua; Lv, Ping; Ma, Kangtao; Zhou, Chunyan; Gao, Xuejun

    2010-07-30

    Research highlights: {yields} {beta}-Catenin/LEF1 complex could activate enamelin gene transcription. {yields} {beta}-Catenin/LEF1 can directly bind to enamelin 5' regulatory region. {yields} Wnt/{beta}-catenin signaling can upregulate enamelin expression in ameloblast-like cells. -- Abstract: Enamelin is an ameloblast-specific matrix protein believed to play essential roles in enamel formation. However, mechanisms of enamelin transcription regulation are not clear. {beta}-Catenin/LEF1 is a key transcriptional complex involved in tooth development. In this study, the role of {beta}-catenin/LEF1 in enamelin expression was investigated. The 5'-flanking region of the mouse enamelin gene was analyzed and cloned. Co-transfection analysis and mutation assays revealed that two conserved LEF1 responsive elements located at -1002 and -597 bp upstream of the enamelin translation initiation site could augment transcriptional activity of the enamelin. The interaction between the enamelin elements and {beta}-catenin/LEF1 was further confirmed by electrophoresis mobility shift assays and chromatin immunoprecipitation assays. In addition, LiCl treatment induced nuclear translocation of {beta}-catenin and elevated endogenous enamelin expression in mouse ameloblast-like cells. The results suggested that Wnt/{beta}-catenin signaling could function in enamelin gene expression by direct interaction through two conserved LEF1 responsive elements on the enamelin gene in ameloblast-like cells.

  13. Ameloblastic fibrosarcoma of the upper jaw: Report of a rare case with long-term follow-up

    PubMed Central

    Khalili, Maryam; Shakib, Pouyan Amini

    2013-01-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant mixed odontogenic tumor which is usually considered as the malignant counterpart of ameloblastic fibroma. Only mesenchymal component represents sarcomatous alterations and ameloblast-like epithelial nest remains bland in AFS. Here, we report a case of AFS in a 26-year-old man in the maxilla, which was regarded as an uncommon location for this tumor. After 2 years follow up, no evidence of recurrence was noted. We also emphasize on comprehensive clinical, radiographic, and histopathologic evaluation of such patients rather than immunohistochemical staining to make an accurate diagnosis. PMID:23878574

  14. Tight junctions in differentiating ameloblasts and odontoblasts differentially express ZO-1, occludin, and claudin-1 in early odontogenesis of rat molars.

    PubMed

    João, Silvia M A; Arana-Chavez, Victor E

    2004-04-01

    Little is known about the expression of associated proteins during the assembly of tight junctions (TJs). We studied the distribution of ZO-1, occludin, and claudin-1 between differentiating ameloblasts and odontoblasts in molar tooth germs from 1- to 3-day-old rats by confocal laser scanning microscopy. Immunoreactivity for ZO-1 was strong at proximal and distal junctional complexes of differentiating ameloblasts, while it was weak and punctuate at the distal region of differentiating odontoblasts. Occludin was immunoreactive at distal and proximal complexes of early differentiating ameloblasts and at distal regions of differentiating odontoblasts. However, in more advanced stages, occludin was only evident at the proximal complex of ameloblasts. Claudin-1 was strongly detected at the proximal complex but it was weak at distal complex of late differentiating ameloblasts. Thus, our results showed that ZO-1, occludin, and claudin-1 are differentially expressed as TJs assemble for regulating polarity and/or paracellular permeability in differentiating ameloblasts and odontoblasts.

  15. Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model.

    PubMed

    Bori, E; Guo, J; Rácz, R; Burghardt, B; Földes, A; Kerémi, B; Harada, H; Steward, M C; Den Besten, P; Bronckers, A L J J; Varga, G

    2016-05-01

    Formation and growth of hydroxyapatite crystals during amelogenesis generate a large number of protons that must be neutralized, presumably by HCO3 (-)ions transported from ameloblasts into the developing enamel matrix. Ameloblasts express a number of transporters and channels known to be involved in HCO3 (-)transport in other epithelia. However, to date, there is no functional evidence for HCO3 (-)transport in these cells. To address questions related to HCO3 (-)export from ameloblasts, we have developed a polarized 2-dimensional culture system for HAT-7 cells, a rat cell line of ameloblast origin. HAT-7 cells were seeded onto Transwell permeable filters. Transepithelial resistance was measured as a function of time, and the expression of transporters and tight junction proteins was investigated by conventional and quantitative reverse transcription polymerase chain reaction. Intracellular pH regulation and HCO3 (-)transport were assessed by microfluorometry. HAT-7 cells formed epithelial layers with measureable transepithelial resistance on Transwell permeable supports and expressed claudin-1, claudin-4, and claudin-8-key proteins for tight junction formation. Transport proteins previously described in maturation ameloblasts were also present in HAT-7 cells. Microfluorometry showed that the HAT-7 cells were polarized with a high apical membrane CO2 permeability and vigorous basolateral HCO3 (-)uptake, which was sensitive to Na(+)withdrawal, to the carbonic anhydrase inhibitor acetazolamide and to H2DIDS inhibition. Measurements of transepithelial HCO3 (-)transport showed a marked increase in response to Ca(2+)- and cAMP-mobilizing stimuli. Collectively, 2-dimensional HAT-7 cell cultures on permeable supports 1) form tight junctions, 2) express typical tight junction proteins and electrolyte transporters, 3) are functionally polarized, and 4) can accumulate HCO3 (-)ions from the basolateral side and secrete them at the apical membrane. These studies provide

  16. Ameloblast Modulation and Transport of Cl⁻, Na⁺, and K⁺ during Amelogenesis.

    PubMed

    Bronckers, A L J J; Lyaruu, D; Jalali, R; Medina, J F; Zandieh-Doulabi, B; DenBesten, P K

    2015-12-01

    Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na(+)K(+)-dependent calcium transporter NCKX4 and the Na(+)-dependent HPO4 (2-) (Pi) cotransporter NaPi-2b. To regulate pH, ameloblasts express anion exchanger 2 (Ae2a,b), chloride channel Cftr, and amelogenins that can bind protons. Exposure to fluoride or null mutation of Cftr, Ae2a,b, or Amelx each results in formation of hypomineralized enamel. We hypothesized that enamel hypomineralization associated with disturbed pH regulation results from reduced ion transport by NCKX4 and NaPi-2b. This was tested by correlation analyses among the levels of Ca, Pi, Cl, Na, and K in forming enamel of mice with null mutation of Cftr, Ae2a,b, and Amelx, according to quantitative x-ray electron probe microanalysis. Immunohistochemistry, polymerase chain reaction analysis, and Western blotting confirmed the presence of apical NaPi-2b and Nckx4 in maturation-stage ameloblasts. In wild-type mice, K levels in enamel were negatively correlated with Ca and Cl but less negatively or even positively in fluorotic enamel. Na did not correlate with P or Ca in enamel of wild-type mice but showed strong positive correlation in fluorotic and nonfluorotic Ae2a,b- and Cftr-null enamel. In hypomineralizing enamel of all models tested, 1) Cl(-) was strongly reduced; 2) K(+) and Na(+) accumulated (Na(+) not in Amelx-null enamel); and 3) modulation was delayed or blocked. These results suggest that a Na(+)K(+)-dependent calcium transporter (likely NCKX4) and a Na(+)-dependent Pi transporter (potentially NaPi-2b) located in ruffle-ended ameloblasts operate in a coordinated way with the pH-regulating machinery to transport Ca(2+), Pi, and bicarbonate into maturation-stage enamel. Acidification and/or associated physicochemical/electrochemical changes in ion levels in enamel fluid near the apical ameloblast membrane may

  17. Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model.

    PubMed

    Bori, E; Guo, J; Rácz, R; Burghardt, B; Földes, A; Kerémi, B; Harada, H; Steward, M C; Den Besten, P; Bronckers, A L J J; Varga, G

    2016-05-01

    Formation and growth of hydroxyapatite crystals during amelogenesis generate a large number of protons that must be neutralized, presumably by HCO3 (-)ions transported from ameloblasts into the developing enamel matrix. Ameloblasts express a number of transporters and channels known to be involved in HCO3 (-)transport in other epithelia. However, to date, there is no functional evidence for HCO3 (-)transport in these cells. To address questions related to HCO3 (-)export from ameloblasts, we have developed a polarized 2-dimensional culture system for HAT-7 cells, a rat cell line of ameloblast origin. HAT-7 cells were seeded onto Transwell permeable filters. Transepithelial resistance was measured as a function of time, and the expression of transporters and tight junction proteins was investigated by conventional and quantitative reverse transcription polymerase chain reaction. Intracellular pH regulation and HCO3 (-)transport were assessed by microfluorometry. HAT-7 cells formed epithelial layers with measureable transepithelial resistance on Transwell permeable supports and expressed claudin-1, claudin-4, and claudin-8-key proteins for tight junction formation. Transport proteins previously described in maturation ameloblasts were also present in HAT-7 cells. Microfluorometry showed that the HAT-7 cells were polarized with a high apical membrane CO2 permeability and vigorous basolateral HCO3 (-)uptake, which was sensitive to Na(+)withdrawal, to the carbonic anhydrase inhibitor acetazolamide and to H2DIDS inhibition. Measurements of transepithelial HCO3 (-)transport showed a marked increase in response to Ca(2+)- and cAMP-mobilizing stimuli. Collectively, 2-dimensional HAT-7 cell cultures on permeable supports 1) form tight junctions, 2) express typical tight junction proteins and electrolyte transporters, 3) are functionally polarized, and 4) can accumulate HCO3 (-)ions from the basolateral side and secrete them at the apical membrane. These studies provide

  18. Immune-based Therapy Clinical Trials in Hepatocellular Carcinoma

    PubMed Central

    Liu, Dai; Staveley-O’Carroll, Kevin F.; Li, Guangfu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality and continues to increase. Current standard of care for patients with HCC only provides limited therapeutic benefit. Development of innovative strategies is urgently needed. Experience with immunotherapy in HCC is quite early, but rapidly rise in the recent 15 years. Multifaceted immune-based approaches have shown efficacy in achieving disease regression, representing the most promising new treatment approach. Here, we classify the ongoing or completed clinical trials in HCC in terms of the immune strategies to be used and assess their clinical outcomes. The generated information may be helpful in the design of future immune-based therapies for achieving ideal tumor control and maximizing anti-tumor immunity. PMID:26877890

  19. Peripheral ameloblastic fibro-odontoma or peripheral developing complex odontoma: report of a case.

    PubMed

    Reibel, Jesper; Grønbaek, Anni B; Poulsen, Sven

    2011-11-01

    BACKGROUND. Peripheral (extraosseous) odontogenic tumors are rare. CASE REPORT. This report describes a case which illustrates the clinical and histopathological features of a lesion in an 8-year-old, healthy Caucasian girl that on purely morphological grounds would seem to be an ameloblastic fibro-odontoma, but may represent a case of a peripheral developing complex odontoma. CONCLUSION. Conservative surgical enucleation of the lesion was followed by unbcomplicated healing and no recurrence was seen.

  20. Ameloblastic secretion and calcification of the enamel layer in shark teeth.

    PubMed

    Kemp, N E

    1985-05-01

    Tooth primordia at early stages of mineralization in the sharks Negaprion brevirostris and Triaenodon obesus were examined electron microscopically for evidence of ameloblastic secretion and its relation to calcification of the enamel (enameloid) layer. Ameloblasts are polarized with most of the mitochondria and all of the Golgi dictyosomes localized in the infranuclear end of the cell toward the squamous outer cells of the enamel organ. Endoplasmic reticular membranes and ribosomes are also abundant in this region. Ameloblastic vesicles bud from the Golgi membranes and evidently move through perinuclear and supranuclear zones to accumulate at the apical end of the cell. The vesicles secrete their contents through the apical cell membrane in merocrine fashion and appear to contribute precursor material both for the basal lamina and the enameline matrix. The enamel layer consists of four zones: a juxta-laminar zone containing newly polymerized mineralizing fibrils (tubules); a pre-enamel zone of assembly of matrix constituents; palisadal zones of mineralizing fibrils (tubules); and interpalisadal zones containing granular amorphous matrix, fine unit fibrils, and giant cross-banded fibers with a periodicity of 17.9 nm. It seems probable that amorphous, non-mineralizing fibrillar and mineralizing fibrillar constituents of the matrix are all products of ameloblastic secretion. Odontoblastic processes are tightly embedded in the matrix of the palisadal zones and do not appear to be secretory at the stages investigated. The shark tooth enamel layer is considered homologous with that of other vertebrates with respect to origin of its mineralizing fibrils from the innerental epithelium. The term enameloid is appropriate to connote the histological distinction that the enamel layer contains odontoblastic processes but should not signify that shark tooth enamel is a modified type of dentine. How amelogenins and/or enamelins secreted by amelo- blasts in the shark and other

  1. Type VII collagen deficiency causes defective tooth enamel formation due to poor differentiation of ameloblasts.

    PubMed

    Umemoto, Hiroko; Akiyama, Masashi; Domon, Takanori; Nomura, Toshifumi; Shinkuma, Satoru; Ito, Kei; Asaka, Takuya; Sawamura, Daisuke; Uitto, Jouni; Uo, Motohiro; Kitagawa, Yoshimasa; Shimizu, Hiroshi

    2012-11-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone. Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries. We examined the tooth enamel structure of an RDEB patient by scanning electron microscopy. It showed irregular enamel prisms, indicating structural enamel defects. To elucidate the pathomechanisms of enamel defects due to COL7 deficiency, we investigated tooth formation in Col7a1(-/-) and COL7-rescued humanized mice that we have established. The enamel from Col7a1(-/-) mice had normal surface structure. The enamel calcification and chemical composition of Col7a1(-/-) mice were similar to those of the wild type. However, transverse sections of teeth from the Col7a1(-/-) mice showed irregular enamel prisms, which were also observed in the RDEB patient. Furthermore, the Col7a1(-/-) mice teeth had poorly differentiated ameloblasts, lacking normal enamel protein-secreting Tomes' processes, and showed reduced mRNA expression of amelogenin and other enamel-related molecules. These enamel abnormalities were corrected in the COL7-rescued humanized mice expressing a human COL7A1 transgene. These findings suggest that COL7 regulates ameloblast differentiation and is essential for the formation of Tomes' processes. Collectively, COL7 deficiency is thought to disrupt epithelial-mesenchymal interactions, leading to defective ameloblast differentiation and enamel malformation in RDEB patients.

  2. Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.

    PubMed

    Miyazaki, Kanako; Yoshizaki, Keigo; Arai, Chieko; Yamada, Aya; Saito, Kan; Ishikawa, Masaki; Xue, Han; Funada, Keita; Haruyama, Naoto; Yamada, Yoshihiko; Fukumoto, Satoshi; Takahashi, Ichiro

    2016-01-01

    Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex. PMID:27015268

  3. Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.

    PubMed

    Miyazaki, Kanako; Yoshizaki, Keigo; Arai, Chieko; Yamada, Aya; Saito, Kan; Ishikawa, Masaki; Xue, Han; Funada, Keita; Haruyama, Naoto; Yamada, Yoshihiko; Fukumoto, Satoshi; Takahashi, Ichiro

    2016-01-01

    Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex.

  4. Ameloblastic Fibro-Odontoma in a 4-Year-Old Boy

    PubMed Central

    Ghandehari-Motlagh, Mehdi; Khosravi, Zahra; Meighani, Ghasem; Baradaran-Nakhjavani, Yahya

    2016-01-01

    Introduction Ameloblastic fibro-odontoma (AFO) is defined as a benign odontogenic tumor with slow growing behavior. Its prevalence is rare. AFO is characterized by histologic features of ameloblastic fibroma (AF) with the formation of enamel and dentine. Case Presentation This is a case report of AFO accompanied with a number of impacted deciduous teeth and its management in a 4-year old boy. Examination of oral cavity revealed an extensive swelling from midline to left deciduous maxillary first molar, covered with normal mucosa. Radiographic examination showed a well-defined mixed radiolucent-radiopaque lesion that extended horizontally from midline to mesial border of the left maxillary primary first molar and vertically from alveolar crest to the floor of nose. The differential diagnosis was odontoma (ameloblastic fibro-odontoma, complex odontoma). Surgical enucleation and curettage was performed under general anesthesia. Histopathologic sections show bone trabeculae in marrow spaces. There was myxoid matrix in some spaces which contained odontogenic epithelial cells. These findings led to diagnosis of AFO. No sign of recurrence has been observed during the 12-month follow-up period. Conclusion Although AFO is a rare tumor, it is more prevalent in childrenʼs jaw. Conservative surgical treatment allowed the normal development of teeth. PMID:27307963

  5. Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation

    PubMed Central

    Arai, Chieko; Yamada, Aya; Saito, Kan; Ishikawa, Masaki; Xue, Han; Funada, Keita; Haruyama, Naoto; Yamada, Yoshihiko; Fukumoto, Satoshi; Takahashi, Ichiro

    2016-01-01

    Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex. PMID:27015268

  6. Hepatocellular carcinoma review: Current treatment, and evidence-based medicine

    PubMed Central

    Raza, Ali; Sood, Gagan K

    2014-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC including curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach. In the past few years with significant advances in surgical treatments and locoregional therapies, the short-term survival of HCC has improved but the recurrent disease remains a big problem. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. For patients with advanced disease, sorafenib is the only approved therapy, but novel systemic molecular targeted agents and their combinations are emerging. This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature. PMID:24764650

  7. Effects of chronic fluoride exposure on morphometric parameters defining the stages of amelogenesis and ameloblast modulation in rat incisors.

    PubMed

    Smith, C E; Nanci, A; Denbesten, P K

    1993-10-01

    The response of ameloblasts to long-term (6 weeks) exposure to 100 ppm fluoride was examined in continuously erupting mandibular incisors of female Sprague-Dawley rats as compared to control rats receiving a similar diet (Teklad L-356) but no sodium fluoride in their drinking water. After treatment, animals from both groups were perfused intravascularly with glutaraldehyde, and the incisors were removed and processed for light microscope morphometric analyses directly from 1 microns thick Epon sections. Other animals were injected intravenously with calcein (green fluorescence) followed 4 hours later by xylenol orange (red fluorescence) in order to reveal smooth-ended ameloblast modulation bands and thereby allow quantification of parameters related to the creation and movement of modulation waves within the maturation zone of these teeth. The results indicated that rat incisors expressed four major changes in normal amelogenesis which could be attributed to the chronic fluoride treatment. First, ameloblasts produced a thinner than normal enamel layer by the time they completed the secretory stage and entered the maturation stage of amelogenesis. Second, enamel organ cells within the maturation zone, especially those from the papillary layer, were shorter in height than normal. Third, ameloblasts related to maturing enamel in areas where it was partially soluble and/or fully soluble in EDTA modulated at a rate that was much slower than normal. In some locations ameloblasts remained ruffle-ended for as much as 30% longer than normal per cycle. This upset the usual pattern such that fewer total modulation cycles were completed per unit time by these ameloblasts. Fourth, enamel proteins were lost from the maturing enamel layer at a rate that was about 40% slower than normal. The data suggested that ameloblasts detected the delay in the extracellular breakdown and/or loss of enamel proteins and they responded by remaining ruffle-ended for longer intervals than usual

  8. Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization.

    PubMed

    Soares, Maria; Madeira, Sara; Correia, Jorge; Peleteiro, Maria; Cardoso, Fátima; Ferreira, Fernando

    2016-06-01

    Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p < 0.001), contrasting with the triple negative basal-like subtype, that was associated with larger and poorly differentiated tumors (p < 0.001), and with the presence of necrotic areas in the tumoral lesion (p = 0.003). In the survival analysis, cats with Luminal A subtype presented the highest survival time (mean OS = 943.6 days) and animals with triple negative basal-like subtype exhibited the lowest survival time (OS mean = 368.9 days). Moreover, two thirds (64%, 32/50) of the queens with multiple primary tumors showed different molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals. Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  9. Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in Gynecologic Oncology Group trials of cisplatin-based chemoradiation

    PubMed Central

    Rose, Peter G; Java, James J; Whitney, Charles W.; Stehman, Frederick B; Lanciano, Rachelle; Thomas, Gillian M

    2015-01-01

    Objective Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer. Methods Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. Results Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies. Conclusion Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation. PMID:25152438

  10. THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) IS EXPRESSED IN MATURATION STAGE AMELOBLASTS, ODONTOBLASTS AND BONE CELLS

    PubMed Central

    Bronckers, Antonius; Kalogeraki, Lida; Jorna, Huub J.N.; Wilke, Martina; Bervoets, Theodore J.; Lyaruu, Donacian M.; Zandieh-Doulabi, Behrouz; DenBesten, Pamela; de Jonge, Hugo

    2010-01-01

    Patients with cystic fibrosis (CF) have mild defects in dental enamel. The gene mutated in these patients is CFTR, a Cl− channel involved in transepithelial salt- and water transport and bicarbonate secretion. We tested the hypothesis that Cftr channels are present and operating in the plasma membranes of mouse ameloblasts. Tissue sections of young mouse jaws and fetal human jaws were immunostained with various anti-Cftr antibodies. Specificity of the antibodies was validated in Cftr-deficient murine and human tissues. Immunostaining for Cftr was obtained in the apical plasma membranes of mouse maturation ameloblasts of both incisor and molar tooth germs. A granular intracellular immunostaining of variable intensity was also noted in bone cells and odontoblasts. In Cftr-deficient mice the incisors were chalky white and eroded much faster than in wild type mice. Histologically, only maturation ameloblasts of incisors were structurally affected in Cftr-deficient mice. Some antibody species gave also a positive cytosolic staining in Cftr-deficient cells. Transcripts of Cftr were found in maturation ameloblasts, odontoblasts and bone cells. Similar data were obtained in forming human dentin and bone. We conclude that Cftr protein locates in the apical plasma membranes of mouse maturation ameloblasts. In mouse incisors Cftr is critical for completion of enamel mineralization and conceivably functions as a regulator of pH during rapid crystal growth. Osteopenia found in CF patients as well as in Cftr-deficient mice is likely associated with defective Cftr operating in bone cells. PMID:20004757

  11. The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in maturation stage ameloblasts, odontoblasts and bone cells.

    PubMed

    Bronckers, Antonius; Kalogeraki, Lida; Jorna, Huub J N; Wilke, Martina; Bervoets, Theodore J; Lyaruu, Donacian M; Zandieh-Doulabi, Behrouz; Denbesten, Pamela; de Jonge, Hugo

    2010-04-01

    Patients with cystic fibrosis (CF) have mild defects in dental enamel. The gene mutated in these patients is CFTR, a Cl(-) channel involved in transepithelial salt and water transport and bicarbonate secretion. We tested the hypothesis that Cftr channels are present and operating in the plasma membranes of mouse ameloblasts. Tissue sections of young mouse jaws and fetal human jaws were immunostained with various anti-Cftr antibodies. Specificity of the antibodies was validated in Cftr-deficient murine and human tissues. Immunostaining for Cftr was obtained in the apical plasma membranes of mouse maturation ameloblasts of both incisor and molar tooth germs. A granular intracellular immunostaining of variable intensity was also noted in bone cells and odontoblasts. In Cftr-deficient mice the incisors were chalky white and eroded much faster than in wild type mice. Histologically, only maturation ameloblasts of incisors were structurally affected in Cftr-deficient mice. Some antibody species gave also a positive cytosolic staining in Cftr-deficient cells. Transcripts of Cftr were found in maturation ameloblasts, odontoblasts and bone cells. Similar data were obtained in forming human dentin and bone. We conclude that Cftr protein locates in the apical plasma membranes of mouse maturation ameloblasts. In mouse incisors Cftr is critical for completion of enamel mineralization and conceivably functions as a regulator of pH during rapid crystal growth. Osteopenia found in CF patients as well as in Cftr-deficient mice is likely associated with defective Cftr operating in bone cells.

  12. Odontogenic carcinoma with dentinoid: a new odontogenic carcinoma.

    PubMed

    Mosqueda-Taylor, Adalberto; Neville, Brad W; Tatemoto, Yukihiro; Ogawa, Ikuko; Takata, Takashi

    2014-12-01

    Dentinoid is an integral part of some odontogenic tumors. This article describes the clinico-pathological features of three cases of odontogenic carcinomas with dentinoid (OCD). A comparison of these with previously reported cases of dentinoid-producing epithelial odontogenic tumors allowed us to identify another six cases that may be considered as examples of OCD. Six cases occurred in the mandible and three in the maxilla, all developing behind the canines. There was no sex predilection (five men and four women; age range 14-61 years, mean 38.1). Pain or discomfort was mentioned in five cases, four of which showed tooth resorption. All cases appeared initially as well-defined radiolucencies, five of which showed variable amounts of calcified material. Recurrences were recorded in three instances, but no evidence of metastasis has been found. Seven cases were composed predominantly or entirely of clear cells, usually with minimal cellular atypia and variable mitotic activity; however, in all cases there was evidence of tumor infiltration into adjacent tissues, including the presence of perineural invasion in two tumors. Those cases in which no reference was made to the presence of clear cells exhibited evident mitotic activity and cellular pleomorphism. The epithelium in OCD does not produce buds or enamel organ-like structures such as those found in ameloblastic fibro-dentinoma and this tumor does not contain a mesenchyme-like connective tissue resembling dental papilla as observed in several mixed odontogenic tumors. Based on the existing data and the present series of cases, OCD appears to represent a distinct entity. PMID:25409850

  13. Prognostic value of DNA repair based stratification of hepatocellular carcinoma

    PubMed Central

    Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

    2016-01-01

    Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

  14. Personalized Clinical Trials in Hepatocellular Carcinoma Based on Biomarker Selection

    PubMed Central

    Zhang, Bingnan; Finn, Richard S.

    2016-01-01

    Background Since the approval of sorafenib there have been numerous failures of new agents in Phase III studies for treatment of advanced hepatocellular carcinoma (HCC). These studies have generally ignored the molecular heterogeneity of HCC and they have not enrolled patients based on predictive markers of response. The development of molecular targeted therapeutics in HCC needs to model the approach that has been taken with great success in other solid tumors, to decrease the likelihood of failure in future studies. Summary Here we review the paradigm taken with novel targeted agents in other solid tumors and highlight ongoing studies in HCC that are incorporating biomarkers in clinical development. Key Messages With the appreciation of the molecular diversity of HCC, clinical development of new agents in HCC will need to be targeted towards those patients who are most likely to benefit. This strategy, based on biomarkers for patient selection, is more likely to yield positive results and mitigate the risk of continued negative Phase III studies. PMID:27493897

  15. Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization.

    PubMed

    Björnson, Elias; Mukhopadhyay, Bani; Asplund, Anna; Pristovsek, Nusa; Cinar, Resat; Romeo, Stefano; Uhlen, Mathias; Kunos, George; Nielsen, Jens; Mardinoglu, Adil

    2015-12-01

    Hepatocellular carcinoma (HCC) is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM) for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB) and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1) in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC. PMID:26655911

  16. Report of four cases of ameloblastic fibro-odontoma in mandible and discussion of the literature about the treatment.

    PubMed

    Pontes, Helder Antonio Rebelo; Pontes, Flavia Sirotheau Correa; Lameira, Aladim Gomes; Salim, Rodrigo Alves; Carvalho, Pedro Luiz de; Guimarães, Douglas Magno; Pinto, Décio Dos Santos

    2012-02-01

    The ameloblastic fibro-odontoma is defined as a tumour with the general features of the ameloblastic fibroma but that also contains enamel and dentine. AFO normally presents as a painless swelling in the posterior portion of the maxilla or mandible. Radiographs show a well-defined radiolucent area containing various amounts of radiopaque material of irregular size and form. The most appropriate treatment for a large AFO has not been completely determined. This paper reports four large AFO cases and reviews the relevant literature regarding the clinical and surgical features of this lesion.

  17. Chemotherapy responsiveness in a patient with multiply relapsed ameloblastic fibro‐odontosarcoma of the maxilla

    PubMed Central

    Thway, Khin; Mandeville, Henry; Kerawala, Cyrus; MacVicar, David; Chisholm, Julia

    2015-01-01

    Ameloblastic fibro‐odontosarcoma (AFOS) is an extremely rare malignant odontogenic tumor. Complete surgical excision is the treatment of choice. Deaths due to disease recurrence and/or progression are documented. Here, we report the case of a 15‐year‐old female with multiple recurrent AFOS. She responded to chemotherapy with ifosfamide and doxorubicin consolidated by stereotactic reirradiation using cyberknife and remained in complete remission 14 months from the end of reirradiation therapy. Chemotherapy with ifosfamide and doxorubicin should be considered in advanced cases of AFOS. Pediatr Blood Cancer © 2015 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc. PMID:26178860

  18. Ameloblastic fibroma: A rare case appearing as a mixed radiographic image

    PubMed Central

    de Castro, Jurema-Freire-Lisboa; Correia, Andreza-Veruska-Lira; Santos, Lucas-Alexandre-Moraes; Guerra, Luiz-Antônio-Portela; Ramos-Perez, Flávia-Maria-de-Moraes

    2014-01-01

    Ameloblastic fibroma (AF) is a benign tumor of mixed odontogenic origin, which affects predominantly young individuals. AF appearing as a mixed radiographic image is very rare. This report describes a case of AF in a 12-year-old male identified during a routine radiographic exam for orthodontic treatment planning. The panoramic radiography revealed a well-defined multilocular mixed image located in the mandible between the roots of the left mandibular second premolar and first molar. The lesion was excised under local anesthesia. Histopathological analysis revealed islands of epithelial cells and columnar peripheral cells showing a nucleus in inverted polarization, interspersed with spindle-shaped cells and abundant extracellular matrix deposition. No atypia was observed. The diagnosis of AF was established. No tumor recurred up to 30 months after treatment. Although rare, AF should be also considered in the differential diagnosis of mixed radiographic images of the jaws in young patients. Key words:Ameloblastic fibroma, differential diagnosis, incidental finding, mixed image, radiographic features. PMID:25674330

  19. Carcinomas of the base of the tongue: diagnosis using double-contrast radiography of the pharynx

    SciTech Connect

    Apter, A.J.; Levine, M.S.; Glick, S.N.

    1984-04-01

    A barium examination is frequently performed as the primary screening study on patients with carcinoma of the base of the tongue who present with dysphagia. Because of the limitations of the conventional barium study in visualizing the pharynx, double-contrast views of this region are routinely included as part of the standard barium examination on all patients with pharyngeal dysphagia. With this technique, six carcinomas of the base of the tongue were detected, including four ulcerating and two exophytic lesions. The normal and abnormal appearance of the tongue base on double-contrast radiography of the pharynx is described.

  20. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    PubMed

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

  1. A network-based method for identifying prognostic gene modules in lung squamous carcinoma

    PubMed Central

    Zhang, Kaitai; Wang, Guiqi; Zhang, Lei; An, Ning; Cheng, Shujun

    2016-01-01

    Similarities in gene expression between both developing embryonic and precancerous tissues and cancer tissues may help identify much-needed biomarkers and therapeutic targets in lung squamous carcinoma. In this study, human lung samples representing ten successive time points, from embryonic development to carcinogenesis, were used to construct global gene expression profiles. Differentially expressed genes with similar expression in precancerous and cancer samples were identified. Using a network-based greedy searching algorithm to analyze the training cohort (n = 69) and three independent testing cohorts, we successfully identified a significant 22-gene module in which expression levels were correlated with overall survival in lung squamous carcinoma patients. PMID:26919109

  2. Ultrastructural and immunocytochemical characterization of ameloblast-enamel adhesion at maturation stage in amelogenesis in Macaca fuscata tooth germ.

    PubMed

    Sawada, Takashi

    2015-12-01

    Maturation-stage ameloblasts are firmly bound to the tooth enamel by a basal lamina-like structure. The mechanism underlying this adhesion, however, remains to be fully clarified. The goal of this study was to investigate the mechanism underlying adhesion between the basal lamina-like structure and the enamel in monkey tooth germ. High-resolution immunogold labeling was performed to localize amelotin and laminin 332 at the interface between ameloblasts and tooth enamel. Minute, electron-dense strands were observed on the enamel side of the lamina densa, extending into the degrading enamel matrix to produce a well-developed fibrous layer (lamina fibroreticularis). In un-demineralized tissue sections, mineral crystals smaller than those in the bulk of the enamel were observed adhering to these strands where they protruded into the surface enamel. Immunogold particles reactive for amelotin were preferentially localized on these strands in the fibrous layer. On the other hand, those for laminin 332 were localized solely in the lamina densa; none were observed in the fibrous layer. These results suggest that the fibrous layer of the basal lamina-like structure is partly composed of amelotin molecules, and that these molecules facilitate ameloblast-enamel adhesion by promoting mineralization of the fibrous layer during the maturation stage of amelogenesis. PMID:26357954

  3. Reconstructing impairment of secretory ameloblast function in porcine teeth by analysis of morphological alterations in dental enamel

    PubMed Central

    Witzel, Carsten; Kierdorf, Uwe; Dobney, Keith; Ervynck, Anton; Vanpoucke, Sofie; Kierdorf, Horst

    2006-01-01

    We studied the relationship between the macroscopic appearance of hypoplastic defects in the dental enamel of wild boar and domestic pigs, and microstructural enamel changes, at both the light and the scanning electron microscopic levels. Deviations from normal enamel microstructure were used to reconstruct the functional and related morphological changes of the secretory ameloblasts caused by the action of stress factors during amelogenesis. The deduced reaction pattern of the secretory ameloblasts can be grouped in a sequence of increasingly severe impairments of cell function. The reactions ranged from a slight enhancement of the periodicity of enamel matrix secretion, over a temporary reduction in the amount of secreted enamel matrix, with reduction of the distal portion of the Tomes' process, to either a temporary or a definite cessation of matrix formation. The results demonstrate that analysis of structural changes in dental enamel allows a detailed reconstruction of the reaction of secretory ameloblasts to stress events, enabling an assessment of duration and intensity of these events. Analysing the deviations from normal enamel microstructure provides a deeper insight into the cellular changes underlying the formation of hypoplastic enamel defects than can be achieved by mere inspection of tooth surface characteristics alone. PMID:16822273

  4. Biomarker-based ovarian carcinoma typing: a histological investigation in the Ovarian Tumor Tissue Analysis consortium

    PubMed Central

    Köbel, Martin; Kalloger, Steve E.; Lee, Sandra; Duggan, Máire A.; Kelemen, Linda E.; Prentice, Leah; Kalli, Kimberly R.; Fridley, Brooke L.; Visscher, Daniel W.; Keeney, Gary L.; Vierkant, Robert A.; Cunningham, Julie M.; Chow, Christine; Ness, Roberta B.; Moysich, Kirsten; Edwards, Robert; Modugno, Francesmary; Bunker, Clareann; Wozniak, Eva L.; Benjamin, Elizabeth; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gilks, C. Blake; Huntsman, David G.; Ramus, Susan J.; Goode, Ellen L.

    2014-01-01

    Background Ovarian carcinoma is composed of five major histological types which associate with outcome and predict therapeutic response. Our aim was to evaluate histological type assessments across centres participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods Tissue microarrays (TMAs) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was performed for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histological type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma (EC) by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of EC compared to HGSC became significant (RR 0.60, 95% CI 0.37–0.93, p=0.021), consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions Research cohorts, particularly those across different centres within consortia, show significant variability in original histological type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. PMID:23880734

  5. Ameloblastic fibrosarcoma of the mandible: a case report and brief review of the literature.

    PubMed

    Loya-Solis, Abelardo; González-Colunga, Karla Judith; Pérez-Rodríguez, Cynthia M; Ramírez-Ochoa, Natalie Sofía; Ceceñas-Falcón, Luis; Barboza-Quintana, Oralia

    2015-01-01

    Ameloblastic fibrosarcoma is an uncommon odontogenic tumor composed of a benign epithelial component and a malignant ectomesenchymal component most frequently seen in the third and fourth decades of life. It mainly presents as a painful maxillary or mandibular swelling. Radiographs show a radiolucent mass with ill-defined borders. Radical surgical excision and long-term follow-up are the suggested treatment. We report the case of a 22-year-old female with a 2-month history of an asymptomatic swelling in her left mandible. Examination revealed an exophytic growth measuring 3 × 3 cm extending from the mandibular left first premolar to the second molar. The patient underwent a left hemimandibular resection. Histopathological examination revealed a biphasic tumor composed of inconspicuous islands of benign odontogenic epithelium and an abundant malignant mesenchymal component with marked cellularity, nuclear pleomorphism, hyperchromatism, and moderate mitotic figures with clear margins; one year after the surgical procedure, the patient is clinically and radiologically disease-free.

  6. Ameloblastic Fibrosarcoma of the Mandible: A Case Report and Brief Review of the Literature

    PubMed Central

    Loya-Solis, Abelardo; González-Colunga, Karla Judith; Pérez-Rodríguez, Cynthia M.; Ramírez-Ochoa, Natalie Sofía; Ceceñas-Falcón, Luis; Barboza-Quintana, Oralia

    2015-01-01

    Ameloblastic fibrosarcoma is an uncommon odontogenic tumor composed of a benign epithelial component and a malignant ectomesenchymal component most frequently seen in the third and fourth decades of life. It mainly presents as a painful maxillary or mandibular swelling. Radiographs show a radiolucent mass with ill-defined borders. Radical surgical excision and long-term follow-up are the suggested treatment. We report the case of a 22-year-old female with a 2-month history of an asymptomatic swelling in her left mandible. Examination revealed an exophytic growth measuring 3 × 3 cm extending from the mandibular left first premolar to the second molar. The patient underwent a left hemimandibular resection. Histopathological examination revealed a biphasic tumor composed of inconspicuous islands of benign odontogenic epithelium and an abundant malignant mesenchymal component with marked cellularity, nuclear pleomorphism, hyperchromatism, and moderate mitotic figures with clear margins; one year after the surgical procedure, the patient is clinically and radiologically disease-free. PMID:25861504

  7. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

    PubMed

    Bardet, Claire; Courson, Frédéric; Wu, Yong; Khaddam, Mayssam; Salmon, Benjamin; Ribes, Sandy; Thumfart, Julia; Yamaguti, Paulo M; Rochefort, Gael Y; Figueres, Marie-Lucile; Breiderhoff, Tilman; Garcia-Castaño, Alejandro; Vallée, Benoit; Le Denmat, Dominique; Baroukh, Brigitte; Guilbert, Thomas; Schmitt, Alain; Massé, Jean-Marc; Bazin, Dominique; Lorenz, Georg; Morawietz, Maria; Hou, Jianghui; Carvalho-Lobato, Patricia; Manzanares, Maria Cristina; Fricain, Jean-Christophe; Talmud, Deborah; Demontis, Renato; Neves, Francisco; Zenaty, Delphine; Berdal, Ariane; Kiesow, Andreas; Petzold, Matthias; Menashi, Suzanne; Linglart, Agnes; Acevedo, Ana Carolina; Vargas-Poussou, Rosa; Müller, Dominik; Houillier, Pascal; Chaussain, Catherine

    2016-03-01

    Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.

  8. MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization

    PubMed Central

    Fan, Yi; Zhou, Yachuan; Zhou, Xuedong; Sun, Feifei; Gao, Bo; Wan, Mian; Zhou, Xin; Sun, Jianxun; Xu, Xin; Cheng, Lei; Crane, Janet

    2015-01-01

    Enamel mineralization is accompanied by the release of protons into the extracellular matrix, which is buffered to regulate the pH value in the local microenvironment. The present study aimed to investigate the role of microRNA 224 (miR-224) as a regulator of SLC4A4 and CFTR, encoding the key buffering ion transporters, in modulating enamel mineralization. miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR. Overexpression of miR-224 downregulated SLC4A4 and CFTR expression in cultured human epithelial cells. A microRNA luciferase assay confirmed the specific binding of miR-224 to the 3′ untranslated regions (UTRs) of SLC4A4 and CFTR mRNAs, thereby inhibiting protein translation. miR-224 agomir injection in mouse neonatal incisors resulted in normal enamel length and thickness, but with disturbed organization of the prism structure and deficient crystal growth. Moreover, the enamel Ca/P ratio and microhardness were markedly reduced after miR-224 agomir administration. These results demonstrate that miR-224 plays a pivotal role in fine tuning enamel mineralization by modulating SLC4A4 and CFTR to maintain pH homeostasis and support enamel mineralization. PMID:26055330

  9. Fibronectin accelerates the growth and differentiation of ameloblast lineage cells in vitro.

    PubMed

    Tabata, Makoto J; Matsumura, Tatsushi; Fujii, Takafumi; Abe, Makoto; Kurisu, Kojiro

    2003-12-01

    During tooth development, the growth and differentiation of ameloblast lineage (AL) cells are regulated by epithelial-mesenchymal interactions. To examine the dynamic effects of components of the basement membrane, which is the extracellular matrix (ECM) lying between the epithelium and mesenchyme, we prepared AL cells from the epithelial layer sheet of mandibular incisors of postnatal day 7 rats and cultured them on plates coated with type IV collagen, laminin-1, or fibronectin. The growth of AL cells was supported by type IV collagen and fibronectin but not by laminin-1 in comparison with that on type I collagen as a reference. Clustering and differentiation of AL cells were observed on all matrices examined. AL cells showed normal growth and differentiation at low cell density on fibronectin but not on type I collagen. Furthermore, the population of cytokeratin 14-positive cells on fibronectin was lower than that on other ECM components, suggesting that fibronectin may be a modulator to accelerate the differentiation of AL cells. After the cells had been cultured for 9 days on fibronectin, crystal-like structures were observed. These structures overlaid the cell clusters and were positive for von Kossa staining. These findings indicate that each matrix component has a regulative role in the proliferation and differentiation of AL cells and that fibronectin causes the greatest acceleration of AL cell differentiation.

  10. Terahertz transmission vs reflection imaging and model-based characterization for excised breast carcinomas

    PubMed Central

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas K.

    2016-01-01

    This work presents experimental and analytical comparison of terahertz transmission and reflection imaging modes for assessing breast carcinoma in excised paraffin-embedded human breast tissue. Modeling for both transmission and reflection imaging is developed. The refractive index and absorption coefficient of the tissue samples are obtained. The reflection measurements taken at the system’s fixed oblique angle of 30° are shown to be a hybridization of TE and TM modes. The models are validated with transmission spectroscopy at fixed points on fresh bovine muscle and fat tissues. Images based on the calculated absorption coefficient and index of refraction of bovine tissue are successfully compared with the terahertz magnitude and phase measured in the reflection mode. The validated techniques are extended to 20 and 30 μm slices of fixed human lobular carcinoma and infiltrating ductal carcinoma mounted on polystyrene microscope slides in order to investigate the terahertz differentiation of the carcinoma with non-cancerous tissue. Both transmission and reflection imaging show clear differentiation in carcinoma versus healthy tissue. However, when using the reflection mode, in the calculation of the thin tissue properties, the absorption is shown to be sensitive to small phase variations that arise due to deviations in slide and tissue thickness and non-ideal tissue adhesion. On the other hand, the results show that the transmission mode is much less sensitive to these phase variations. The results also demonstrate that reflection imaging provides higher resolution and more clear margins between cancerous and fibroglandular regions, cancerous and fatty regions, and fibroglandular and fatty tissue regions. In addition, more features consistent with high power pathology images are exhibited in the reflection mode images.

  11. Terahertz transmission vs reflection imaging and model-based characterization for excised breast carcinomas

    PubMed Central

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas K.

    2016-01-01

    This work presents experimental and analytical comparison of terahertz transmission and reflection imaging modes for assessing breast carcinoma in excised paraffin-embedded human breast tissue. Modeling for both transmission and reflection imaging is developed. The refractive index and absorption coefficient of the tissue samples are obtained. The reflection measurements taken at the system’s fixed oblique angle of 30° are shown to be a hybridization of TE and TM modes. The models are validated with transmission spectroscopy at fixed points on fresh bovine muscle and fat tissues. Images based on the calculated absorption coefficient and index of refraction of bovine tissue are successfully compared with the terahertz magnitude and phase measured in the reflection mode. The validated techniques are extended to 20 and 30 μm slices of fixed human lobular carcinoma and infiltrating ductal carcinoma mounted on polystyrene microscope slides in order to investigate the terahertz differentiation of the carcinoma with non-cancerous tissue. Both transmission and reflection imaging show clear differentiation in carcinoma versus healthy tissue. However, when using the reflection mode, in the calculation of the thin tissue properties, the absorption is shown to be sensitive to small phase variations that arise due to deviations in slide and tissue thickness and non-ideal tissue adhesion. On the other hand, the results show that the transmission mode is much less sensitive to these phase variations. The results also demonstrate that reflection imaging provides higher resolution and more clear margins between cancerous and fibroglandular regions, cancerous and fatty regions, and fibroglandular and fatty tissue regions. In addition, more features consistent with high power pathology images are exhibited in the reflection mode images. PMID:27699136

  12. Enamel pits in hamster molars, formed by a single high fluoride dose, are associated with a perturbation of transitional stage ameloblasts

    PubMed Central

    Lyaruu, D.M.; Vermeulen, L.; Stienen, N.; Bervoets, T.J.M.; DenBesten, P.K.; Bronckers, A.L.J.J.

    2013-01-01

    Excessive intake of fluoride (F) by young children results in formation of enamel subsurface porosities and pits, called enamel fluorosis. In this study, we used a single high dose of fluoride administered to hamster pups, to determine the stage of ameloblasts most affected by fluoride, and whether pit formation was related to F-related sub-ameloblastic cyst formation. Hamster pups received a single subcutaneous injection of either 20 mg or 40 mg NaF/kg body weights, were sacrificed 24 h later, and the number of cysts formed in the first molars counted. Other pups were sacrificed 8 days after F-injection when the first molars had just erupted, to score for enamel defects. All F-injected pups formed enamel defects in the upper half of the cusps in a dose-dependent way. After injection of 20 mg NaF/kg an average of 2.2 white spots per molar was found but no pits. At 40 mg NaF/kg, almost 4.5 spots per molar were counted as well as 2 pits per molar. The defects in erupted enamel were located in the upper half of the cusps, sites where cysts had formed at the transition stage of ameloblast differentiation. These results suggest that transitional ameloblasts, located between secretory and maturation stage ameloblasts, are most sensitive to the effects of a single high dose of fluoride. Fluoride- induced cysts formed earlier at the pre-secretory stage were not correlated to either white spots or enamel pits, suggesting that damaged ameloblasts overlying a fluoride induced cyst regenerate and continue to form enamel. PMID:22947666

  13. Fluctuations in surface pH of maturing rat incisor enamel are a result of cycles of H(+)-secretion by ameloblasts and variations in enamel buffer characteristics.

    PubMed

    Damkier, Helle H; Josephsen, Kaj; Takano, Yoshiro; Zahn, Dirk; Fejerskov, Ole; Frische, Sebastian

    2014-03-01

    It is disputed if ameloblasts in the maturation zone of the enamel organ mainly buffer protons released by hydroxyapatite (HA) crystal growth or if they periodically secrete protons to create alternating acidic and alkaline conditions. The latter hypothesis predicts alternating pH regimes in maturing enamel, which would be affected by pharmacological interference with ameloblast H(+)-secretion. This study tests these predictions. Colorimetric pH-indicators and ratiometric fluorometry were used to measure surface pH in maturation zone enamel of rat incisors. Alternating acidic (down to pH6.24±0.06) and alkaline zones (up to pH7.34±0.08) were found along the tooth coinciding with ameloblast morphological cycles. Underlying the cyclic pattern, a gradual decrease in pH towards the incisal edge was seen. Vinblastine or FR167356 (H(+)-ATPase-inhibitor) disturbed ameloblast acid-secretion, especially in the early parts of acidic zones. Enamel surface pH reflects the titration state of surface PO4(3-)-ions. At the pH-values observed, PO4(3-) would be protonated (pKa>12) and HA dissolved. However, by molecular dynamics simulations we estimate the pKa of HPO4(2-) at an ideal HA surface to be 4.3. The acidic pH measured at the enamel surface may thus only dissolve non-perfect domains of HA crystals in which PO4(3-) is less electrostatically shielded. During repeated alkaline/acidic cycles, near-perfect HA-domains may therefore gradually replace less perfect HA-domains resulting in near-perfect HA-crystals. In conclusion, cyclic changes in ameloblast H(+)-secretion and the degree of enamel maturation determine enamel surface pH. This is in accordance with a hypothesis implicating H(+)-ATPase mediated acid-secretion by ameloblasts.

  14. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.

    PubMed Central

    Evans, D G; Ladusans, E J; Rimmer, S; Burnell, L D; Thakker, N; Farndon, P A

    1993-01-01

    There are many potential complications which have been reported in association with the naevoid basal cell carcinoma syndrome. We have been able to show the relative frequencies of these problems in a population based study of 84 cases in the north west of England. The major complications of basal cell carcinomas and jaw cysts occur in over 90% of patients by 40 years of age, but may both occur before 10 years of age. Less well described complications are ovarian calcification or fibroma (24%), medulloblastoma (5%), cardiac fibroma (3%), cleft palate (5%), and ophthalmic abnormalities such as squint or cataract (26%). This study more clearly defines the possible complications of the syndrome and gives clearer guidelines for counselling and screening affected and at risk persons. Images PMID:8326488

  15. Induction of enamel matrix protein expression in an ameloblast cell line co-cultured with a mesenchymal cell line in vitro.

    PubMed

    Matsumoto, Asako; Harada, Hidemitsu; Saito, Masahiro; Taniguchi, Akiyoshi

    2011-01-01

    Interactions between epithelium and mesenchyme are important for organ and tissue development. In this study, in order to mimic interactions between epithelium and mesenchyme during native tooth development, we constructed three-dimensional culture systems in vitro using a collagen membrane. Two types of collagen membrane-based in vitro culture systems were constructed in which dental epithelial and dental follicle cell lines were cultured. One co-culture method involved inoculation of one cell line into one side of the collagen membrane, and the other cell line into the opposite side of the membrane (sandwich co-culture). As a control, the second method involved culture of one of the cell lines on a culture dish and the second cell line on a collagen membrane, facing away from the first cell line (separate co-culture). The HAT-7 cells were also grown as a monolayer culture on collagen. Ameloblast differentiation in these cultures was investigated by analysis of the mRNA and/or protein expression of ameloblastin and amelogenin. Our results suggest that interaction of epithelial and mesenchymal cells via the extracellular matrix is important for tooth differentiation in vitro. Our culture system should be a useful method for investigation of epithelial-mesenchymal interactions.

  16. Induction of enamel matrix protein expression in an ameloblast cell line co-cultured with a mesenchymal cell line in vitro.

    PubMed

    Matsumoto, Asako; Harada, Hidemitsu; Saito, Masahiro; Taniguchi, Akiyoshi

    2011-01-01

    Interactions between epithelium and mesenchyme are important for organ and tissue development. In this study, in order to mimic interactions between epithelium and mesenchyme during native tooth development, we constructed three-dimensional culture systems in vitro using a collagen membrane. Two types of collagen membrane-based in vitro culture systems were constructed in which dental epithelial and dental follicle cell lines were cultured. One co-culture method involved inoculation of one cell line into one side of the collagen membrane, and the other cell line into the opposite side of the membrane (sandwich co-culture). As a control, the second method involved culture of one of the cell lines on a culture dish and the second cell line on a collagen membrane, facing away from the first cell line (separate co-culture). The HAT-7 cells were also grown as a monolayer culture on collagen. Ameloblast differentiation in these cultures was investigated by analysis of the mRNA and/or protein expression of ameloblastin and amelogenin. Our results suggest that interaction of epithelial and mesenchymal cells via the extracellular matrix is important for tooth differentiation in vitro. Our culture system should be a useful method for investigation of epithelial-mesenchymal interactions. PMID:21082283

  17. Identification of HSPA8 as a candidate biomarker for endometrial carcinoma by using iTRAQ-based proteomic analysis

    PubMed Central

    Shan, Nianchun; Zhou, Wei; Zhang, Shufen; Zhang, Yu

    2016-01-01

    Although there are advances in diagnostic, predictive, and therapeutic strategies, discovering protein biomarker for early detection is required for improving the survival rate of the patients with endometrial carcinoma. In this study, we identify proteins that are differentially expressed between the Stage I endometrial carcinoma and the normal pericarcinous tissues by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. Totally, we screened 1,266 proteins. Among them, 103 proteins were significantly overexpressed, and 30 were significantly downexpressed in endometrial carcinoma. Using the bioinformatics analysis, we identified a list of proteins that might be closely associated with endometrial carcinoma, including CCT7, HSPA8, PCBP2, LONP1, PFN1, and EEF2. We validated the gene overexpression of these molecules in the endometrial carcinoma tissues and found that HSPA8 was most significantly upregulated. We further validated the overexpression of HSPA8 by using immunoblot analysis. Then, HSPA8 siRNA was transferred into the endometrial cancer cells RL-95-2 and HEC-1B. The depletion of HSPA8 siRNAs significantly reduced cell proliferation, promoted cell apoptosis, and suppressed cell growth in both cell lines. Taken together, HSPA8 plays a vital role in the development of endometrial carcinoma. HSPA8 is a candidate biomarker for early diagnosis and therapy of Stage I endometrial carcinoma. PMID:27110132

  18. EMMPRIN/CD147 deficiency disturbs ameloblast-odontoblast cross-talk and delays enamel mineralization.

    PubMed

    Khaddam, Mayssam; Huet, Eric; Vallée, Benoît; Bensidhoum, Morad; Le Denmat, Dominique; Filatova, Anna; Jimenez-Rojo, Lucia; Ribes, Sandy; Lorenz, Georg; Morawietz, Maria; Rochefort, Gael Y; Kiesow, Andreas; Mitsiadis, Thimios A; Poliard, Anne; Petzold, Matthias; Gabison, Eric E; Menashi, Suzanne; Chaussain, Catherine

    2014-09-01

    Tooth development is regulated by a series of reciprocal inductive signaling between the dental epithelium and mesenchyme, which culminates with the formation of dentin and enamel. EMMPRIN/CD147 is an Extracellular Matrix MetalloPRoteinase (MMP) INducer that mediates epithelial-mesenchymal interactions in cancer and other pathological processes and is expressed in developing teeth. Here we used EMMPRIN knockout (KO) mice to determine the functional role of EMMPRIN on dental tissue formation. We report a delay in enamel deposition and formation that is clearly distinguishable in the growing incisor and associated with a significant reduction of MMP-3 and MMP-20 expression in tooth germs of KO mice. Insufficient basement membrane degradation is evidenced by a persistent laminin immunostaining, resulting in a delay of both odontoblast and ameloblast differentiation. Consequently, enamel volume and thickness are decreased in adult mutant teeth but enamel maturation and tooth morphology are normal, as shown by micro-computed tomographic (micro-CT), nanoindentation, and scanning electron microscope analyses. In addition, the dentino-enamel junction appears as a rough calcified layer of approximately 10±5μm thick (mean±SD) in both molars and growing incisors of KO adult mice. These results indicate that EMMPRIN is involved in the epithelial-mesenchymal cross-talk during tooth development by regulating the expression of MMPs. The mild tooth phenotype observed in EMMPRIN KO mice suggests that the direct effect of EMMPRIN may be limited to a short time window, comprised between basement membrane degradation allowing direct cell contact and calcified matrix deposition.

  19. Atypical culture-negative skull base osteomyelitis masquerading as advanced nasopharyngeal carcinoma.

    PubMed

    See, Anna; Tan, Tiong Yong; Gan, Eng Cern

    2016-01-01

    Skull base osteomyelitis typically arises as a complication of otogenic or sinonasal infections in immunocompromised patients. A much rarer entity, atypical skull base osteomyelitis is not associated with an obvious infective source. Atypical and culture-negative skull base osteomyelitis is even rarer and hampers diagnosis, as its clinical presentation is remarkably similar to skull base neoplasms. We report a case of extensive skull base osteomyelitis with orbital apex syndrome and multiple lower cranial nerve palsies which initially masqueraded as possible advanced nasopharyngeal carcinoma. Extensive investigations and consult with an infectious diseases specialist aided in elucidation of the correct diagnosis. Through this article, we emphasize that skull base osteomyelitis must be considered in the setting of headache, cranial neuropathies, elevated inflammatory markers and abnormal imaging findings. Early tissue sampling for histology, stainings and cultures and prompt appropriate treatment may prevent or arrest further complications. PMID:27178515

  20. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation.

    PubMed

    Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi

    2016-01-01

    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling. PMID:27030100

  1. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

    PubMed Central

    Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi

    2016-01-01

    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling. PMID:27030100

  2. Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

    NASA Astrophysics Data System (ADS)

    Xiong, S. Y.; Yang, J. G.; Zhuang, J.

    2011-10-01

    In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

  3. Clear Cell Mypepithelial Carcinoma of the Base Tongue Managed by the Mandible Preserving Pull-Through Oropharyngectomy Approach.

    PubMed

    Krishnamurthy, Arvind

    2015-09-01

    Myoepithelial carcinoma (MC) is rare disease that comprises of only about 2 % of all salivary gland carcinomas and MC that focally or predominantly displays clear cell-type tumor cells are considered as CCMC. We recently got to treat a rare case of a base tongue clear cell myoepithelial carcinoma. (CCMC) Our patient, to the best of our knowledge is the second case of base tongue CCMC and the first with metastatic involvement of the cervical lymph nodes. We successfully managed the tumor using the "mandible preserving pull-through oropharyngectomy approach" Knowledge of the different surgical approaches and techniques is thus vital for better oncologic, functional and aesthetic outcomes following surgery for tumors especially in challenging sub sites like the oropharynx.

  4. Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

    PubMed

    Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

    2006-11-01

    We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

  5. Large ameloblastic fibro-odontoma in a 7-year-old girl with analysis of 108 cases

    PubMed Central

    Kirjavainen, Antti; Tuovinen, Veikko; Sándor, George K.

    2016-01-01

    Background: Odontogenic tumors such as ameloblastic fibro-odontoma (AFO) are rare conditions in children and are often asymptomatic. AFOs are found by routine clinical and radiological examination or when they cause obvious intra- or extra-oral swelling. Materials and Methods: A case of an AFO in a 7-year-old girl is described, and 107 cases from the literature and this report are analyzed. Results: The total of 108 cases revealed the average age at presentation of AFO to be 6.3 years in boys and 9.6 years in girls. There was a slight male predilection and AFO lesions most often occurred in the posterior mandible. AFO was almost always associated with an unerupted tooth or teeth. Conclusions: While the recurrence rate of AFO was found to be 5.5%, long-term postoperative clinical and radiological follow-up is advised to ensure no future signs of aggressive recurrence. PMID:27563600

  6. Long-term eradication of locally recurrent invasive follicular thyroid carcinoma after taxane-based concomitant chemoradiotherapy.

    PubMed

    Tulloch-Reid, Marshall; Skarulis, Monica C; Sherman, Steven I; Sarlis, Nicholas J; Santarpia, Libero

    2009-11-01

    A 46-year-old woman with history of radioiodine-refractory follicular thyroid carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease. She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT), which was well tolerated, resulting in complete remission and freedom from residual or recurrent FTC for longer than 5 years until her last follow-up at age 52. This case highlights the possibility of combining taxane-based chemotherapy with definitive radiotherapy (as CRT) for the management of locally aggressive recurrences in poorly differentiated thyroid carcinoma, thereby resulting in rapid and persistent disease eradication. Even in the light of recent data on the potential benefit of novel targeted therapy agents in poorly differentiated thyroid carcinoma, this approach in similar clinical settings deserves future investigation. PMID:20032418

  7. Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma

    PubMed Central

    Gao, Jian-Jun; Shi, Zhen-Yan; Xia, Ju-Feng; Inagaki, Yoshinori; Tang, Wei

    2015-01-01

    Sorafenib is the only and standard systematic chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC) at the current stage. Although sorafenib showed survival benefits in large randomized phase III studies, its clinical benefits remain modest and most often consist of temporary tumor stabilization, indicating that more effective first-line treatment regimens or second-line salvage therapies are required. The molecular pathogenesis of HCC is very complex, involving hyperactivated signal transduction pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR and aberrant expression of molecules such as receptor tyrosine kinases and histone deacetylases. Simultaneous or sequential abrogation of these critical pathways or the functions of these key molecules involved in angiogenesis, proliferation, and apoptosis may yield major improvements in the management of HCC. In this review, we summarize the emerging sorafenib-based combined molecule targeting for HCC treatment and analyze the rationales of these combinations. PMID:26576091

  8. Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

    PubMed Central

    Yang, Xi; Zhu, Hongcheng; Qin, Qin; Yang, Yuehua; Yang, Yan; Cheng, Hongyan; Sun, Xinchen

    2015-01-01

    This study was designed to identify candidate single-nucleotide polymorphisms (SNPs) that may affect the susceptibility to esophageal squamous cell carcinoma (ESCC) and elucidate their potential mechanisms to generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset for ESCC, which included 453,852 SNPs from 1898 ESCC patients and 2100 control subjects of Chinese population, was reviewed. The identify candidate causal SNPs and pathways (ICSNPathway) analysis identified seven candidate SNPs, five genes, and seven pathways, which together revealed seven hypothetical biological mechanisms. The three strongest hypothetical biological mechanisms were as follows: rs4135113 → TDG → BASE EXCISION REPAIR; rs1800450 → MBL2 → MONOSACCHARIDE BINDING; and rs3769823 → CASP8 → d4gdiPathway. The GWAS dataset was evaluated using the ICSNPathway, which showed seven candidate SNPs, five genes, and seven pathways that may contribute to the susceptibility of patients to ESCC. PMID:25431829

  9. A conditional transposon-based insertional mutagenesis screen for hepatocellular carcinoma-associated genes in mice

    PubMed Central

    Keng, Vincent W.; Villanueva, Augusto; Chiang, Derek Y.; Dupuy, Adam J.; Ryan, Barbara J.; Matise, Ilze; Silverstein, Kevin A.T.; Sarver, Aaron; Starr, Timothy K.; Akagi, Keiko; Tessarollo, Lino; Collier, Lara S.; Powers, Scott; Lowe, Scott W.; Jenkins, Nancy A.; Copeland, Neal G.; Llovet, Josep M.; Largaespada, David A.

    2009-01-01

    Here we describe a Sleeping Beauty (SB) transposition system that utilizes a conditional SB transposase allele, which can be activated by Cre recombinase to drive the transposition of a mutagenic transposon in virtually any tissue and control the type of cancer produced. To demonstrate the potential of this system for modeling cancer in mice, we used it to screen for hepatocellular carcinoma (HCC) associated genes in mice by specifically limiting SB transposition to the liver. Among 8,060 non-redundant insertions subsequently cloned from 68 tumor nodules we identified 19 highly significant candidate disease loci, which encode genes like EGFR and MET that are known HCC genes and others like UBE2H that are not strongly implicated in HCC but represent potential new therapeutic targets for treating this neoplasm. With these improvements, transposon-based insertional mutagenesis now offers great potential for better understanding the cancer genome and for identifying new targets for therapeutic development. PMID:19234449

  10. Mitomycin-C- or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

    SciTech Connect

    Olivatto, Luis O.; Cabral, Vania; Rosa, Arthur; Bezerra, Marcos; Santarem, Erick; Fassizoli, Ana; Castro, Leonaldson; Simoes, Jose Humberto; Small, Isabele A.; Ferreira, Carlos Gil

    2011-02-01

    Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m{sup 2} 120-hour infusion or 1,000 mg/m{sup 2} 96-hour infusion) plus CP (100 mg/m{sup 2}) on the first day of each cycle or MMC (10-15 mg/m{sup 2}) on the first day of Cycle 1 was administered concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.

  11. Enhanced effectiveness of tocotrienol-based nano-emulsified system for topical delivery against skin carcinomas.

    PubMed

    Pham, Jimmy; Nayel, Amy; Hoang, Christina; Elbayoumi, Tamer

    2016-06-01

    The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® - incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.

  12. Magneto-reactance based detection of MnO nanoparticle-embedded Lewis lung carcinoma cells

    NASA Astrophysics Data System (ADS)

    Devkota, J.; Howell, M.; Mukherjee, P.; Srikanth, H.; Mohapatra, S.; Phan, M. H.

    2015-05-01

    We demonstrate the capacity of detecting magnetically weak manganese oxide (MnO) nanoparticles and the Lewis lung carcinoma (LLC) cancer cells that have taken up these nanoparticles using a novel biosensor based on the magneto-reactance (MX) effect of a soft ferromagnetic amorphous ribbon with a microhole-patterned surface. While the magnetic moment of the MnO nanoparticles is relatively small, and a magneto-impedance based sensor fails to detect them in solution (0.05 mg/ml manganese oxide lipid micellar nanoparticles) and inside cells at low concentrations (8.25 × 104 cells/ml), the detection of these nanoparticles and the LLC cells containing them is achieved with the MX-based sensor, which, respectively, reaches the detection sensitivity of ˜3.6% and 2.8% as compared to the blank cells. Since the MnO nanoparticles are a promising contrast agent for magnetic resonance imaging (MRI) of lung cells, the MX-based biosensing technique can be developed as a pre-detection method for MRI of lung cancer cells.

  13. BINNING SOMATIC MUTATIONS BASED ON BIOLOGICAL KNOWLEDGE FOR PREDICTING SURVIVAL: AN APPLICATION IN RENAL CELL CARCINOMA

    PubMed Central

    Kim, Dokyoon; Li, Ruowang; Dudek, Scott M.; Wallace, John R.; Ritchie, Marylyn D.

    2014-01-01

    Enormous efforts of whole exome and genome sequencing from hundreds to thousands of patients have provided the landscape of somatic genomic alterations in many cancer types to distinguish between driver mutations and passenger mutations. Driver mutations show strong associations with cancer clinical outcomes such as survival. However, due to the heterogeneity of tumors, somatic mutation profiles are exceptionally sparse whereas other types of genomic data such as miRNA or gene expression contain much more complete data for all genomic features with quantitative values measured in each patient. To overcome the extreme sparseness of somatic mutation profiles and allow for the discovery of combinations of somatic mutations that may predict cancer clinical outcomes, here we propose a new approach for binning somatic mutations based on existing biological knowledge. Through the analysis using renal cell carcinoma dataset from The Cancer Genome Atlas (TCGA), we identified combinations of somatic mutation burden based on pathways, protein families, evolutionary conversed regions, and regulatory regions associated with survival. Due to the nature of heterogeneity in cancer, using a binning strategy for somatic mutation profiles based on biological knowledge will be valuable for improved prognostic biomarkers and potentially for tailoring therapeutic strategies by identifying combinations of driver mutations. PMID:25592572

  14. Diagnostic Value of Liquid-Based Cytology in Urothelial Carcinoma Diagnosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Li; Fu, Sheng-Jun

    2015-01-01

    Objective To evaluate the value of liquid-based cytology (LBC) in the diagnosis of urothelial carcinoma. Method Diagnostic studies were searched for the diagnostic value of LBC in urothelial carcinoma in PubMed, Embase, Cochrane Library, Web of Science, CBM and CNKI. The latest retrieval date was September 2014. The data were extracted and the quality of the included studies was independently assessed by 2 reviewers. Stata 13 software was used to perform the statistical analysis. The research was conducted in compliance with the PRISMA statement. Result Nineteen studies, which included 8293 patients, were evaluated. The results of the meta-analysis showed that the pooled sensitivity and specificity of LBC were 0.58 (0.51–0.65) and 0.96 (0.93–0.98), respectively. The diagnostic odds ratio (DOR) was 31 (18–56) and the area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.83 (0.80–0.86). The post-test probability was 80% when a positive diagnosis was made. Compared with high grade urothelial carcinoma (HGUC), the sensitivity of detecting low-grade urothelial carcinoma (LGUC) was significantly lower, risk ratio of sensitivity was 0.54 (0.43–0.66), P<0.001. However, no significant sensitivity improvement was observed with LBC when compared with traditional cytospin cytology, risk ratio was 1.03 (0.94–1.14), P = 0.524. Conclusion Despite LBC having a pooled 58% positive rate for urothelial carcinoma diagnosis in our meta-analysis, no significant improvement in sensitivity was observed based on the studies evaluated. Further research is needed to validate these findings. PMID:26241896

  15. Network-Based Analysis of Nutraceuticals in Human Hepatocellular Carcinomas Reveals Mechanisms of Chemopreventive Action

    PubMed Central

    Michailidou, M; Melas, IN; Messinis, DE; Klamt, S; Alexopoulos, LG; Kolisis, FN; Loutrari, H

    2015-01-01

    Chronic inflammation is associated with the development of human hepatocellular carcinoma (HCC), an essentially incurable cancer. Anti-inflammatory nutraceuticals have emerged as promising candidates against HCC, yet the mechanisms through which they influence the cell signaling machinery to impose phenotypic changes remain unresolved. Herein we implemented a systems biology approach in HCC cells, based on the integration of cytokine release and phospoproteomic data from high-throughput xMAP Luminex assays to elucidate the action mode of prominent nutraceuticals in terms of topology alterations of HCC-specific signaling networks. An optimization algorithm based on SigNetTrainer, an Integer Linear Programming formulation, was applied to construct networks linking signal transduction to cytokine secretion by combining prior knowledge of protein connectivity with proteomic data. Our analysis identified the most probable target phosphoproteins of interrogated compounds and predicted translational control as a new mechanism underlying their anticytokine action. Induced alterations corroborated with inhibition of HCC-driven angiogenesis and metastasis. PMID:26225263

  16. Network-Based Analysis of Nutraceuticals in Human Hepatocellular Carcinomas Reveals Mechanisms of Chemopreventive Action.

    PubMed

    Michailidou, M; Melas, I N; Messinis, D E; Klamt, S; Alexopoulos, L G; Kolisis, F N; Loutrari, H

    2015-06-01

    Chronic inflammation is associated with the development of human hepatocellular carcinoma (HCC), an essentially incurable cancer. Anti-inflammatory nutraceuticals have emerged as promising candidates against HCC, yet the mechanisms through which they influence the cell signaling machinery to impose phenotypic changes remain unresolved. Herein we implemented a systems biology approach in HCC cells, based on the integration of cytokine release and phospoproteomic data from high-throughput xMAP Luminex assays to elucidate the action mode of prominent nutraceuticals in terms of topology alterations of HCC-specific signaling networks. An optimization algorithm based on SigNetTrainer, an Integer Linear Programming formulation, was applied to construct networks linking signal transduction to cytokine secretion by combining prior knowledge of protein connectivity with proteomic data. Our analysis identified the most probable target phosphoproteins of interrogated compounds and predicted translational control as a new mechanism underlying their anticytokine action. Induced alterations corroborated with inhibition of HCC-driven angiogenesis and metastasis. PMID:26225263

  17. A chemotherapy response classifier based on support vector machines for high-grade serous ovarian carcinoma

    PubMed Central

    Zhou, Bo; Guo, En-Song; Yang, Zong-Yuan; Liao, Jing; Ding, Dong; Xu, Qin; Lu, Hao; Meng, Li; Wang, Shi-Xuan; Zhou, Jian-Feng; Xing, Hui; Weng, Dan-Hui; Ma, Ding; Chen, Gang

    2016-01-01

    Long-term outcome of high-grade serous epithelial ovarian carcinoma (HGSOC) remains poor as a result of recurrence and the emergence of drug resistance. Almost all the patients were given the same platinum-based chemotherapy after debulking surgery even though some of them are naturally resistant to the first-line chemotherapy. No method could verify this part of patients right after the surgery currently. In this study, we used 156 paraffin-embedded high-grade HGSOC specimens for immunohistochemical analysis with 37 immunology markers, and association between the expression levels of these markers and the chemoresponse were evaluated. A support vector machine (SVM)-based HGSOC prognostic classifier was then established, and was validated by a 95-patient independent cohort. The classifier was strongly predictive of chemotherapy resistance, and divided patients into low- and high-risk groups with significant differences progression-free survival (PFS) and overall survival (OS). This classifier may provide a potential way to predict the chemotherapy resistance of HGSOC right after the surgery, and then allow clinicians to make optimal clinical decision for those potentially chemoresistant patients. The potential clinical application of this classifier will benefit those patients with primary drug resistance. PMID:26675546

  18. Candidate pathways and genes for nasopharyngeal carcinoma based on bioinformatics study

    PubMed Central

    Chen, Jinhui; Yang, Rui; Zhang, Wei; Wang, Yongping

    2015-01-01

    Purpose: To reveal the potential microRNAs (miRNAs), genes, pathways and regulatory network involved in the process of nasopharyngeal carcinoma (NPC) by using the method of bioinformatics. Methods: Gene expression profiles GSE12452 (31 NPC and 10 normal samples) and GSE53819 (18 NPC and 18 normal samples), as well as miRNA expression profiles GSE32960 (312 NPC and 18 normal samples) and GSE36682 (62 NPC and 6 normal samples) were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) between NPC and normal samples were identified by using t-test based on MATLAB software (FDR < 0.01), followed by pathway enrichment analysis based on DAVID software (P-value < 0.1). Then, DEmiRNA-DEG regulatory network was constructed. Results: A total of 1254 DEGs and 107 DEmiRNAs were identified, respectively. Then, 16 pathways (including cell cycle) and 32 pathways (including pathways in cancer) were enriched by DEGs and target genes of DEmiRNAs, respectively. Furthermore, DEmiRNA-DEG regulatory network was constructed, containing 12 DEmiRNAs (including has-miR-615-3P) and 180 DEGs (including MCM4 and CCNE2). Conclusion: has-miR-615-3p might take part in the pathogenetic process of NPC through regulating MCM4 which is enriched in cell cycle. The DEmiRNAs identified in the present study might serve as new biomarkers for NPC. PMID:25973099

  19. Transarterial chemoembolization for hepatocellular carcinoma: an evidence-based review of its place in therapy.

    PubMed

    Jang, Ji Hye; Lee, Jin-Woo; Hong, Ji Taek; Jin, Young-Joo

    2015-01-01

    Transarterial chemoembolization (TACE) is the standard treatment for patients with Barcelona Clinic Liver Cancer-intermediate stage hepatocellular carcinoma (HCC). The concept of drug-eluting bead TACE builds on the rationale of intratumoral drug delivery, and drug-eluting bead TACE has been shown to provide consistent and reliable results and to significantly diminish systemic drug exposure, liver toxicity, and drug-related adverse events as compared with conventional TACE. Based on the belief that combinations of TACE and other local or systemic therapies have several theoretical advantages, many clinical trials have been conducted to evaluate the effectiveness of TACE in combination with local treatment such as radiofrequency ablation or radiotherapy, and systemic therapy such as sorafenib or another molecular therapy. TACE has also been used as a preoperative adjuvant chemotherapy in patients with HCC to improve survival and as a bridging therapy before liver transplantation to downstage HCC. In the present evidence-based review, the authors summarize the current status of these transcatheter arterial embolic therapies in HCC.

  20. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy.

    PubMed

    Sun, Cheng; Sun, Hao-yu; Xiao, Wei-hua; Zhang, Cai; Tian, Zhi-gang

    2015-10-01

    The mechanisms linking hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) remain largely unknown. Natural killer (NK) cells account for 25%-50% of the total number of liver lymphocytes, suggesting that NK cells play an important role in liver immunity. The number of NK cells in the blood and tumor tissues of HCC patients is positively correlated with their survival and prognosis. Furthermore, a group of NK cell-associated genes in HCC tissues is positively associated with the prolonged survival. These facts suggest that NK cells and HCC progression are strongly associated. In this review, we describe the abnormal NK cells and their functional impairment in patients with chronic HBV and HCV infection, which contribute to the progression of HCC. Then, we summarize the association of NK cells with HCC based on the abnormalities in the numbers and phenotypes of blood and liver NK cells in HCC patients. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of HCC. Finally, we present the current achievements in NK cell immunotherapy conducted in mouse models of liver cancer and in clinical trials, highlighting how chemoimmunotherapy, NK cell transfer, gene therapy, cytokine therapy and mAb therapy improve NK cell function in HCC treatment. It is conceivable that NK cell-based anti-HCC therapeutic strategies alone or in combination with other therapies will be great promise for HCC treatment.

  1. Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma.

    PubMed

    Yao, Wei-Rong; Xu, Shou-Ping; Liu, Bo; Cao, Xiu-Tang; Ren, Gang; Du, Lei; Zhou, Fu-Gen; Feng, Lin-Chun; Qu, Bao-Lin; Xie, Chuan-Bin; Ma, Lin

    2015-01-01

    The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (D mean, V 1, and D 50) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm(3) and 35%, respectively. The interweekly parotid volume varied significantly (p < 0.05). The parotid D mean, V 1, and D 50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid D mean, and weight loss rate are valuable indicators for parotid protection-based replanning.

  2. Analysis of Renal Cell Carcinoma as a First Step for Developing Mass Spectrometry-Based Diagnostics

    NASA Astrophysics Data System (ADS)

    Yoshimura, Kentaro; Chen, Lee Chuin; Mandal, Mridul Kanti; Nakazawa, Tadao; Yu, Zhan; Uchiyama, Takahito; Hori, Hirokazu; Tanabe, Kunio; Kubota, Takeo; Fujii, Hideki; Katoh, Ryohei; Hiraoka, Kenzo; Takeda, Sen

    2012-10-01

    Immediate diagnosis of human specimen is an essential prerequisites in medical routines. This study aimed to establish a novel cancer diagnostics system based on probe electrospray ionization-mass spectrometry (PESI-MS) combined with statistical data processing. PESI-MS uses a very fine acupuncture needle as a probe for sampling as well as for ionization. To demonstrate the applicability of PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell carcinoma (ccRCC) by PESI-MS and processed the data by principal components analysis (PCA). Our system successfully delineated the differences in lipid composition between non-cancerous and cancerous regions. In this case, triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine different individuals, the result being consistent with well-known profiles of ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous regions based on the expression of TAG. These results strongly suggest that PESI-MS will be applicable to cancer diagnosis, especially when the number of data is augmented.

  3. Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract

    PubMed Central

    Kondo, Tsunenori; Takagi, Toshio; Tanabe, Kazunari

    2015-01-01

    Lymphadenectomy for urothelial carcinoma of the upper urinary tract has attracted the attention of physicians. The mapping study of lymphatic spread has shown that a relatively wide area should comprise the regional nodes for tumors of the right renal pelvis or the right upper two-thirds of the ureter. A prospective study showed that an anatomical template-based lymphadenectomy significantly improved patient survival in tumors of the renal pelvis. This benefit was more evident for patients with pT2 stage tumors or higher. The risk of regional node recurrence is significant reduced by template-based lymphadenectomy, which is likely to be associated with improved patient survival. The removal of lymph node micrometastases is assumed to be the reason for therapeutic benefit following lymphadenectomy. The number of resected lymph nodes can be used to assess the quality of lymphadenectomy, but not to determine the extent of lymphadenectomy. The guidelines currently recommend lymphadenectomy for patients with muscle-invasive disease, even though the current recommendation grades are still low. The present limitation of lymphadenectomy is the lack of standardization of the extent of lymphadenectomy and the randomized trials. Further studies are warranted to collect the evidence to support lymphadenectomy. PMID:26677437

  4. Thermal Versus Impedance-Based Ablation of Renal Cell Carcinoma: A Meta-analysis

    SciTech Connect

    Modabber, Milad Martin, Jason; Athreya, Sriharsha

    2013-10-04

    BackgroundPercutaneous radiofrequency ablation (RFA) of renal carcinoma has become an established treatment modality. However, thermal (TB) versus impedance-based (IB)-RF generators have not been previously compared.MethodsA literature search on the application of RFA for renal masses using TB or IB-RF generators was performed. The safety, efficacy, and long-term outcomes of TB versus IB-based RFA were assessed using the outcome measures of technical success, local recurrence rate, complications, and preservation of renal function.ResultsAcross the 27 included studies, pooled results suggested comparable results for technical success (TB-RFA 98.53 % vs. IB-RFA 98.78 %, P = 0.9813). Clinical efficacy results were also similar across both generators (91.0 % TB-RFA vs. 91.5 % IB-RFA; P = 0.73). At follow-up, no differences in renal function (relative risk [RR] 0.5, 95 % confidence interval [CI] 0.45–5.48), and local recurrence (RR 0.717, 95 % CI 0.49–1.50) were observed. The pooled proportion of overall complication rates was 13.1 % for TB-RFA and 11.5 % for IB-RFA.ConclusionNo differences in the observed parameters were found either during surgery or at follow-up.

  5. Genetic Variations in ABCG2 Gene Predict Breast Carcinoma Susceptibility and Clinical Outcomes after Treatment with Anthracycline-Based Chemotherapy

    PubMed Central

    Wu, Huizhe; Liu, Yong; Kang, Hui; Xiao, Qinghuan; Yao, Weifan; Zhao, Haishan; Wang, Enhua; Wei, Minjie

    2015-01-01

    The genetic variants of the ATP-binding cassette, subfamily G, member 2 (ABCG2) are known to be involved in developing cancer risk and interindividual differences in chemotherapeutic response. The polymorphisms in ABCG2 gene were genotyped by using PCR-RFLP assays. We found that ABCG2 G34A GA/AA genotype, C421A AA genotype, and haplotypes 34A-421C and 34G-421A were significantly associated with increased risk for developing breast carcinoma. Furthermore, ABCG2 C421A AA homozygote had a significant enhanced therapeutic response in patients with neoadjuvant anthracycline-based chemotherapy. Moreover, ABCG2 G34A AA genotype carriers displayed a longer OS in ER positive patients or PR positive patients after postoperative anthracycline-based chemotherapy. These results suggested that the ABCG2 polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis for breast carcinoma patients. PMID:26634205

  6. Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases.

    PubMed

    Meder, Lydia; König, Katharina; Fassunke, Jana; Ozretić, Luka; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Heukamp, Lukas C; Buettner, Reinhard

    2015-12-01

    Small cell lung carcinoma (SCLC) is the most aggressive entity of lung cancer. Rapid cancer progression and early formation of systemic metastases drive the deadly outcome of SCLC. Recent advances in identifying oncogenes by cancer whole genome sequencing improved the understanding of SCLC carcinogenesis. However, tumor material is often limited in the clinic. Thus, it is a compulsive issue to improve SCLC diagnostics by combining established immunohistochemistry and next generation sequencing. We implemented amplicon-based next generation deep sequencing in our routine diagnostics pipeline to analyze RB1, TP53, EP300 and CREBBP, frequently mutated in SCLC. Thereby, our pipeline combined routine SCLC histology and identification of somatic mutations. We comprehensively analyzed fifty randomly collected SCLC metastases isolated from trachea and lymph nodes in comparison to specimens derived from primary SCLC. SCLC lymph node metastases showed enhanced proliferation and frequently a collapsed keratin cytoskeleton compared to SCLC metastases isolated from trachea. We identified characteristic synchronous mutations in RB1 and TP53 and non-synchronous CREBBP and EP300 mutations. Our data showed the benefit of implementing deep sequencing into routine diagnostics. We here identify oncogenic drivers and simultaneously gain further insights into SCLC tumor biology.

  7. A Novel Hepatocellular Carcinoma Image Classification Method Based on Voting Ranking Random Forests.

    PubMed

    Xia, Bingbing; Jiang, Huiyan; Liu, Huiling; Yi, Dehui

    2015-01-01

    This paper proposed a novel voting ranking random forests (VRRF) method for solving hepatocellular carcinoma (HCC) image classification problem. Firstly, in preprocessing stage, this paper used bilateral filtering for hematoxylin-eosin (HE) pathological images. Next, this paper segmented the bilateral filtering processed image and got three different kinds of images, which include single binary cell image, single minimum exterior rectangle cell image, and single cell image with a size of n⁎n. After that, this paper defined atypia features which include auxiliary circularity, amendment circularity, and cell symmetry. Besides, this paper extracted some shape features, fractal dimension features, and several gray features like Local Binary Patterns (LBP) feature, Gray Level Co-occurrence Matrix (GLCM) feature, and Tamura features. Finally, this paper proposed a HCC image classification model based on random forests and further optimized the model by voting ranking method. The experiment results showed that the proposed features combined with VRRF method have a good performance in HCC image classification problem.

  8. Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers.

    PubMed

    Dai, Zhi; Zhou, Jian; Qiu, Shuang-Jian; Liu, Yin-Kun; Fan, Jia

    2009-09-01

    More and more new diagnostic biomarkers of hepatocellular carcinoma (HCC) have been found in association with advances in the standardization of 2-DE coupled with MS analysis. However, the diagnosis of HCC is still detected in the late stages of the disease, when treatment options are limited and prognosis is poor. The glycosylation of proteins is known to change in tumor cells during the development of HCC as the result of alterations in the levels of glycosyltransferases, such as increased fucosylation of Golgi Protein 73 and alpha-fetoprotein. These structural changes can influence the function or physiochemical properties of a protein, resulting in abnormal cancer cell behavior. Therefore, identification of HCC-related glycoprotein markers and analysis of glycan structural alterations might assist in the early detection of HCC. Here, we summarize lectin-based glycoproteomic strategies for the discovery of relevant biomarkers of HCC. The carbohydrate-binding specificities of different lectins offer a biological affinity approach that complements existing MS capabilities. These strategies involve the enrichment of glycoproteins or glycopeptides by lectins, followed by releasing carbohydrates with peptide-N-glycosidase F or reductive beta-elimination. The obtained glycopeptides are then identified by automated MS/MS and structural analysis of glycans is performed through modern methods such as quadrupole IT-TOF, MALDI-TOF/TOF and lectin microarray. These strategies will lead to faster and more clinically adaptable tests with greater sensitivity and specificity.

  9. LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma.

    PubMed

    Tsai, Tsung-Heng; Song, Ehwang; Zhu, Rui; Di Poto, Cristina; Wang, Minkun; Luo, Yue; Varghese, Rency S; Tadesse, Mahlet G; Ziada, Dina Hazem; Desai, Chirag S; Shetty, Kirti; Mechref, Yehia; Ressom, Habtom W

    2015-07-01

    Associating changes in protein levels with the onset of cancer has been widely investigated to identify clinically relevant diagnostic biomarkers. In the present study, we analyzed sera from 205 patients recruited in the United States and Egypt for biomarker discovery using label-free proteomic analysis by LC-MS/MS. We performed untargeted proteomic analysis of sera to identify candidate proteins with statistically significant differences between hepatocellular carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the significance of 101 proteins in sera from the same 205 patients through targeted quantitation by MRM on a triple quadrupole mass spectrometer. This led to the identification of 21 candidate protein biomarkers that were significantly altered in both the United States and Egyptian cohorts. Among the 21 candidates, ten were previously reported as HCC-associated proteins (eight exhibiting consistent trends with our observation), whereas 11 are new candidates discovered by this study. Pathway analysis based on the significant proteins reveals upregulation of the complement and coagulation cascades pathway and downregulation of the antigen processing and presentation pathway in HCC cases versus patients with liver cirrhosis. The results of this study demonstrate the power of combining untargeted and targeted quantitation methods for a comprehensive serum proteomic analysis, to evaluate changes in protein levels and discover novel diagnostic biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD001171 (http://proteomecentral.proteomexchange.org/dataset/PXD001171).

  10. A Novel Hepatocellular Carcinoma Image Classification Method Based on Voting Ranking Random Forests

    PubMed Central

    Xia, Bingbing; Jiang, Huiyan; Liu, Huiling; Yi, Dehui

    2016-01-01

    This paper proposed a novel voting ranking random forests (VRRF) method for solving hepatocellular carcinoma (HCC) image classification problem. Firstly, in preprocessing stage, this paper used bilateral filtering for hematoxylin-eosin (HE) pathological images. Next, this paper segmented the bilateral filtering processed image and got three different kinds of images, which include single binary cell image, single minimum exterior rectangle cell image, and single cell image with a size of n⁎n. After that, this paper defined atypia features which include auxiliary circularity, amendment circularity, and cell symmetry. Besides, this paper extracted some shape features, fractal dimension features, and several gray features like Local Binary Patterns (LBP) feature, Gray Level Cooccurrence Matrix (GLCM) feature, and Tamura features. Finally, this paper proposed a HCC image classification model based on random forests and further optimized the model by voting ranking method. The experiment results showed that the proposed features combined with VRRF method have a good performance in HCC image classification problem. PMID:27293477

  11. Tooth Enamel Protein Amelogenin Binds to Ameloblast Cell Membrane-Mimicking Vesicles via its N-terminus

    PubMed Central

    LOKAPPA, SOWMYA BEKSHE; CHANDRABABU, KARTHIK BALAKRISHNA; MORADIAN-OLDAK, JANET

    2015-01-01

    We have recently reported that the extracellular enamel protein amelogenin has affinity to interact with phospholipids and proposed that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities. Here, in order to identify the liposome-interacting domains of amelogenin we designed four different amelogenin mutants containing only a single tryptophan at positions 25, 45, 112 and 161. Circular dichroism studies of the mutants confirmed that they are structurally similar to the wild-type amelogenin. Utilizing the intrinsic fluorescence of single tryptophan residues and fluorescence resonance energy transfer FRET, we analyzed the accessibility and strength of their binding with an ameloblast cell membrane-mimicking model membrane (ACML) and a negatively charged liposome used as a membrane model. We found that amelogenin has membrane-binding ability mainly via its N-terminal, close to residues W25 and W45. Significant blue shift was also observed in the fluorescence of a N-terminal peptide following addition of liposomes. We suggest that, among other mechanisms, enamel malformation in cases of Amelogenesis Imperfecta (AI) with mutations at the N-terminal may be the result of defective amelogenin-cell interactions. PMID:26188506

  12. The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation

    PubMed Central

    Cao, Huojun; Jheon, Andrew; Li, Xiao; Sun, Zhao; Wang, Jianbo; Florez, Sergio; Zhang, Zichao; McManus, Michael T.; Klein, Ophir D.; Amendt, Brad A.

    2013-01-01

    The mouse incisor is a remarkable tooth that grows throughout the animal’s lifetime. This continuous renewal is fueled by adult epithelial stem cells that give rise to ameloblasts, which generate enamel, and little is known about the function of microRNAs in this process. Here, we describe the role of a novel Pitx2:miR-200c/141:noggin regulatory pathway in dental epithelial cell differentiation. miR-200c repressed noggin, an antagonist of Bmp signaling. Pitx2 expression caused an upregulation of miR-200c and chromatin immunoprecipitation assays revealed endogenous Pitx2 binding to the miR-200c/141 promoter. A positive-feedback loop was discovered between miR-200c and Bmp signaling. miR-200c/141 induced expression of E-cadherin and the dental epithelial cell differentiation marker amelogenin. In addition, miR-203 expression was activated by endogenous Pitx2 and targeted the Bmp antagonist Bmper to further regulate Bmp signaling. miR-200c/141 knockout mice showed defects in enamel formation, with decreased E-cadherin and amelogenin expression and increased noggin expression. Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell differentiation and tooth development. PMID:23863486

  13. Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue.

    PubMed

    Sudbø, J; Bankfalvi, A; Bryne, M; Marcelpoil, R; Boysen, M; Piffko, J; Hemmer, J; Kraft, K; Reith, A

    2000-12-01

    Several studies on oral squamous cell carcinomas (OSCC) suggest that the clinical value of traditional histologic grading is limited both by poor reproducibility and by low prognostic impact. However, the prognostic potential of a strictly quantitative and highly reproducible assessment of the tissue architecture in OSCC has not been evaluated. Using image analysis, in 193 cases of T1-2 (Stage I-II) OSCC we retrospectively investigated the prognostic impact of two graph theory-derived structural features: the average Delaunay Edge Length (DEL_av) and the average homogeneity of the Ulam Tree (ELH_av). Both structural features were derived from subgraphs of the Voronoi Diagram. The geometric centers of the cell nuclei were computed, generating a two-dimensional swarm of point-like seeds from which graphs could be constructed. The impact on survival of the computed values of ELH_av and DEL_av was estimated by the method of Kaplan and Meier, with relapse-free survival and overall survival as end-points. The prognostic values of DEL_av and ELH_av as computed for the invasive front, the superficial part of the carcinoma, the total carcinoma, and the normal-appearing oral mucosa were compared. For DEL_av, significant prognostic information was found in the invasive front (p < 0.001). No significant prognostic information was found in superficial part of the carcinoma (p = 0.34), in the carcinoma as a whole (p = 0.35), or in the normal-appearing mucosa (p = 0.27). For ELH_av, significant prognostic information was found in the invasive front (p = 0.01) and, surprisingly, in putatively normal mucosa (p = 0.03). No significant prognostic information was found in superficial parts of the carcinoma (p = 0.34) or in the total carcinoma (p = 0.11). In conclusion, strictly quantitative assessment of tissue architecture in the invasive front of OSCC yields highly prognostic information. PMID:11140700

  14. Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue.

    PubMed

    Sudbø, J; Bankfalvi, A; Bryne, M; Marcelpoil, R; Boysen, M; Piffko, J; Hemmer, J; Kraft, K; Reith, A

    2000-12-01

    Several studies on oral squamous cell carcinomas (OSCC) suggest that the clinical value of traditional histologic grading is limited both by poor reproducibility and by low prognostic impact. However, the prognostic potential of a strictly quantitative and highly reproducible assessment of the tissue architecture in OSCC has not been evaluated. Using image analysis, in 193 cases of T1-2 (Stage I-II) OSCC we retrospectively investigated the prognostic impact of two graph theory-derived structural features: the average Delaunay Edge Length (DEL_av) and the average homogeneity of the Ulam Tree (ELH_av). Both structural features were derived from subgraphs of the Voronoi Diagram. The geometric centers of the cell nuclei were computed, generating a two-dimensional swarm of point-like seeds from which graphs could be constructed. The impact on survival of the computed values of ELH_av and DEL_av was estimated by the method of Kaplan and Meier, with relapse-free survival and overall survival as end-points. The prognostic values of DEL_av and ELH_av as computed for the invasive front, the superficial part of the carcinoma, the total carcinoma, and the normal-appearing oral mucosa were compared. For DEL_av, significant prognostic information was found in the invasive front (p < 0.001). No significant prognostic information was found in superficial part of the carcinoma (p = 0.34), in the carcinoma as a whole (p = 0.35), or in the normal-appearing mucosa (p = 0.27). For ELH_av, significant prognostic information was found in the invasive front (p = 0.01) and, surprisingly, in putatively normal mucosa (p = 0.03). No significant prognostic information was found in superficial parts of the carcinoma (p = 0.34) or in the total carcinoma (p = 0.11). In conclusion, strictly quantitative assessment of tissue architecture in the invasive front of OSCC yields highly prognostic information.

  15. Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

    PubMed

    Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

    2010-01-01

    This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

  16. Prognostic Value of Prevertebral Space Involvement in Nasopharyngeal Carcinoma Based on Intensity-Modulated Radiotherapy

    SciTech Connect

    Zhou Guanqun; Mao YanPing; Chen Lei; Li Wenfei; Liu Lizhi; Sun Ying; Chen Yong; Tian Li; Lin Aihua; Li Li; and others

    2012-03-01

    Purpose: To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: A retrospective review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients underwent magnetic resonance imaging examinations and received IMRT as their primary treatment. Results: In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p < 0.001), skull base (p < 0.001), and paranasal sinuses (p = 0.009) were associated with PSI after multivariate analysis. The 4-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p < 0.0001), 83.9% and 96.4% (p < 0.0001), and 71.6% and 89.6% (p < 0.0001), respectively. Multivariate analysis identified PSI as an independent negative prognostic factor for both OS (HR = 1.478-4.380; p = 0.001) and DMFS (HR = 1.389-4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences between PSI and T3 disease in both OS and DMFS were distinctly significant (p = 0.029 and p = 0.029, respectively). Conclusions: For NPC patients treated with IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS. It seems reasonable that PSI should be classified as a T4 disease on the basis of the current American Joint Committee on Cancer staging classification criteria.

  17. Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols

    PubMed Central

    Galun, Danijel; Basaric, Dragan; Zuvela, Marinko; Bulajic, Predrag; Bogdanovic, Aleksandar; Bidzic, Nemanja; Milicevic, Miroslav

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome. PMID:26380652

  18. Interaction of key pathways in sorafenib-treated hepatocellular carcinoma based on a PCR-array

    PubMed Central

    Liu, Yan; Wang, Ping; Li, Shijie; Yin, Linan; Shen, Haiyang; Liu, Ruibao

    2015-01-01

    This study aimed to identify the key pathways and to explore the mechanism of sorafenib in inhibiting hepatocellular carcinoma (HCC). The gene expression profile of GSE33621, including 6 sorafenib treated group and 6 control samples, was downloaded from the GEO (Gene Expression Omnibus) database. The differentially expressed genes (DEGs) in HCC samples were screened using the ΔΔCt method with the homogenized internal GAPDH. Also, the functions and pathways of DEGs were analyzed using the DAVID. Moreover, the significant pathways of DEGs that involved in HCC were analyzed based on the Latent pathway identification analysis (LPIA). A total of 44 down-regulated DEGs were selected in HCC samples. Also, there were 84 biological pathways that these 44 DEGs involved in. Also, LPIA showed that Osteoclast differentiation and hsa04664-Fc epsilon RI signaling pathway was the most significant interaction pathways. Moreover, Apoptosis, Toll-like receptor signaling pathway, Chagas disease, and T cell receptor signaling pathway were the significant pathways that interacted with hsa04664. In addition, DEGs such as AKT1 (v-akt murine thymoma viral oncogene homolog 1), TNF (tumor necrosis factor), SYK (spleen tyrosine kinase), and PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1 (alpha)) were the common genes that involved in the significant pathways. Several pathway interaction pairs that caused by several downregulated genes such as SYK, PI3K, AKT1, and TNF, were identified play curial role in sorafenib treated HCC. Sorafenib played important inhibition roles in HCC by affecting a complicate pathway interaction network. PMID:26045814

  19. Identification of hub genes and pathways associated with hepatocellular carcinoma based on network strategy

    PubMed Central

    Liu, Jun; Hua, Ping; Hui, Li; Zhang, Li-Li; Hu, Zhen; Zhu, Ying-Wei

    2016-01-01

    The objective of this study was to identify hub genes and pathways associated with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression network. A co-expression network based on differentially expressed (DE) genes of HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL) package. Centrality analyses, for centrality of degree, clustering coefficient, closeness, stress and betweenness for the co-expression network were performed to identify hub genes, and the hub genes were combined together to overcome inconsistent results. Enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Finally, validation of hub genes was conducted utilizing reverse transcription-polymerase chain reaction (RT-PCR) analysis. In total, 260 DE genes between normal controls and HCC patients were obtained and a co-expression network with 154 nodes and 326 edges was constructed. From this, 13 hub genes were identified according to degree, clustering coefficient, closeness, stress and betweenness centrality analysis. It was found that reelin (RELN), potassium voltage-gated channel subfamily J member 10 (KCNJ10) and neural cell adhesion molecule 1 (NCAM1) were common hub genes across the five centralities, and the results of RT-PCR analysis for RELN, KCNJ10 and NCAM1 were consistent with the centrality analyses. Pathway enrichment analysis of DE genes showed that cell cycle, metabolism of xenobiotics by cytochrome P450 and p53 signaling pathway were the most significant pathways. This study may contribute to understanding the molecular pathogenesis of HCC and provide potential biomarkers for its early detection and effective therapies. PMID:27703495

  20. Behavior of substances labeled with /sup 3/H-proline and /sup 3/H-fucose in the cellular processes of odontoblasts and ameloblasts

    SciTech Connect

    Warshawsky, H.; Josephsen, K.

    1981-05-01

    Odontoblasts are cells with single cytoplasmic processes that grow longer as more dentin is elaborated. Ameloblasts also have single processes and it has been postulated that they too grow longer as more enamel is made. Support for this hypothesis was obtained using rat incisors to investigate the behavior of substances labeled with /sup 3/H-proline and /sup 3/H-fucose. A comparison was made between odontoblasts, which have processes known to grow and remain within the dentin, and the ameloblasts whose Tomes' processes are hypothesized to grow and leave remnants in the completed enamel. With /sup 3/H-proline, the odontoblast bodies are labeled at the early time intervals. With /sup 3/H-fucose, the cell bodies are labeled at the early intervals and the newly formed glycoproteins are deposited into the predentin. Almost immediately, these are progressively added to the dentin at the calcification front. With time a gradient of labeling extends from the unlabeled dentin toward the odontoblast bodies. Unlike the behavior of labeled proteins, by 1 and 2 days labeled glycoproteins appear along the entire length of the odontoblast processes. In the enamel, no Tomes' processes are present during maturation. With /sup 3/H-proline, reactions are adjacent to the cells and diffuse toward, but do not reach the dentino-enamel junction by 1 and 2 days. With /sup 3/H-fucose, reactions appear over the enamel near the cells. By 1 and 2 days no diffusive pattern is seen, but grains are concentrated near the dentino-enamel junction, in a region containing holes known to be the beginning of Tomes' processes. Since odontoblast glycoproteins migrate along odontoblast processes, it was postulated that cytoplasmic remnants were present in enamel along which ameloblast glycoproteins could also migrate to reach the holes at the dentino-enamel junction.

  1. Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

    PubMed

    Zhang, Shu-xu; Han, Peng-hui; Zhang, Guo-qian; Wang, Rui-hao; Ge, Yong-bin; Ren, Zhi-gang; Li, Jian-sheng; Fu, Wen-hai

    2014-01-01

    Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

  2. Assessment of carcinoma in the sublingual region based on magnetic resonance imaging.

    PubMed

    Asaumi, Jun-Ichi; Shigehara, Hiroshi; Konouchi, Hironobu; Yanagi, Yoshinobu; Hisatomi, Miki; Matsuzaki, Hidenobu; Kishi, Kanji

    2002-01-01

    In the present study, we attempted to diagnose and detect the extent of tumors in the sublingual region using magnetic resonance imaging (MRI) and dynamic MRI. MRI with or without gadopentetate dimeglumine (Gd-DTPA)-enhancement in seven lesions of the sublingual regions was performed. The seven lesions included four cases of mucoepidermoid carcinoma (mucoepidermoid Ca), two cases of adenoid cystic carcinoma (ACC), and one case of squamous cell carcinoma (SCC). Whether the tumor was malignant or benign, as well as the differential diagnosis, could not be determined on the basis of the MR signals, even when enhancement was performed. Dynamic MRI was performed in five cases, two cases of ACC, two cases of mucoepidermoid Ca, and one case of SCC. The dynamic MRI showed a rapid enhancement at 30-45 sec in all five cases before the normal sublingual gland began to be enhanced. The early phases at 30-45 sec of the dynamic MRI in five cases showed marked enhancement before the normal sublingual glands were enhanced, and therefore could clearly show the extent of the lesions. In conclusion, the dynamic MRI may be useful in differentiating malignant from benign tumors, and in detecting the extent of the tumors in the sublingual carcinomas.

  3. Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma

    PubMed Central

    Liu, Lin; Zheng, Ying-hui; Han, Li; Qin, Shu-Kui

    2016-01-01

    Abstract Background: Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies. Methods: A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events. Results: Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2–19.6%), 9.3% (95%CI 10–28%), and 35.7% (95%CI 27–44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8–21%) in Asian patients and 12.8% (95%CI 6.8–18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients. Conclusions: Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma. PMID:27749557

  4. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

    PubMed

    Choi, Y-W; Bae, S M; Kim, Y-W; Lee, H N; Kim, Y W; Park, T C; Ro, D Y; Shin, J C; Shin, S J; Seo, J-S; Ahn, W S

    2007-01-01

    Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

  5. Preoperative CT-based nomogram for predicting overall survival in women with non-endometrioid carcinomas of the uterine corpus

    PubMed Central

    Lakhman, Yulia; Yakar, Derya; Goldman, Debra A.; Katz, Seth S.; Vargas, Hebert A.; Miccò, Maura; Zheng, Junting; Moskowitz, Chaya S.; Soslow, Robert A.; Hricak, Hedvig; Abu-Rustum, Nadeem R.; Sala, Evis

    2016-01-01

    Purpose To develop a preoperative CT-based nomogram for predicting overall survival (OS) in patients with non-endometrioid carcinomas of the uterine corpus. Methods Waiving informed consent, the institutional review board approved this HIPAA-compliant, retrospective study of 193 women with histopathologically proven uterine papillary serous carcinomas (UPSC), uterine clear cell carcinomas (UCCC), and uterine carcinosarcomas (UCS) who underwent primary surgical resection between May 1998 and December 2011, and had a preoperative CT ≤ 6 weeks before surgery. All CT scans were reviewed for local or/and regional tumor extent, presence of pelvic or/and paraaortic adenopathy, and presence of distant metastases. Univariate survival analysis was performed using log-rank test and Cox regression. Variables shown significant by the univariate analysis were evaluated with the multivariable Cox regression analysis and the results were used to create a nomogram for predicting OS. The predictive accuracy of the nomogram was assessed with the concordance probability index (c-index) and a 3-year calibration plot. Results Mean patient age was 67.2 years (range: 49.0–85.9); histology included UPSC (n=116), UCCC (n=27), and UCS (n=50). Median follow-up was 38.1 months (0.9–168.5 months). At multivariate analysis, patient age, ascites, and omental implants on CT were significant adverse predictors of OS and were used to build the nomogram. Concordance index for the nomogram was 0.640±0.028. Conclusion We developed a nomogram with a good concordance probability at predicting OS based on readily available pretreatment clinical and imaging characteristics. This preoperative nomogram has the potential to improve initial treatment planning and patient counseling. PMID:25549782

  6. Odontogenic ghost cell carcinoma with pulmonary metastasis

    PubMed Central

    Sukumaran, Renu; Somanathan, Thara; Kattoor, Jayasree

    2015-01-01

    Odontogenic ghost cell carcinoma (OGCC) is an exceptionally rare malignant odontogenic epithelial tumor. It is characterized by ameloblastic-like islands of epithelial cells with aberrant keratinization in the form of ghost cells with varying amounts of dysplastic dentin. Malignant histological characteristics include infiltration, cellular pleomorphism, numerous mitosis and necrosis. Its biological behavior varies from slow-growing locally invasive lesions to rapidly growing highly aggressive tumors. OGCC metastasizing to distant sites is extremely rare. Only three cases of metastasis have been reported in literature. We are reporting the case of a 54-year-old male patient who presented with tender swelling in the malar region. Histopathological examination revealed OGCC and he received postoperative radiotherapy. Two years later, he presented with a lung mass. Biopsy from the lung lesion showed the same morphology as that of maxillary tumor with scattered ghost cells. This case points to the aggressive behavior of OGCC and its metastatic potential. It also highlights the need for long-term follow-up of these patients. PMID:26980967

  7. Adenoid cystic carcinoma of the base of the tongue: Late metastasis to the pancreas

    PubMed Central

    Falk, Gavin A.; El-Hayek, Kevin; Morris-Stiff, Gareth; Tuthill, Ralph J.; Winans, Charles G.

    2010-01-01

    Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumor of the salivary glands. We present a 64-year-old gentleman with ACC of the tongue who following resection and radiotherapy, presented 10 years later with a lung metastasis and underwent operative intervention and further radiotherapy. Five years later he presented with obstructive jaundice found to be metastatic ACC. We believe this to be the first report of an ACC metastasizing to the pancreas. PMID:22096672

  8. Current status and perspectives of immune-based therapies for hepatocellular carcinoma

    PubMed Central

    Aerts, Maridi; Benteyn, Daphné; Van Vlierberghe, Hans; Thielemans, Kris; Reynaert, Hendrik

    2016-01-01

    Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a “curative” treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this “immunotolerant” organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future. PMID:26755874

  9. Construction and development of a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma.

    PubMed

    Li, Feng; Liu, Yan-Hong; Li, Yan-Wen; Li, Yue-Hui; Xie, Ping-Li; Ju, Qiang; Chen, Lin; Li, Guan-Cheng

    2012-12-01

    We present a detailed method for constructing a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma. Two novel mammalian library vectors pcDNA3-CHm and pcDNA3-CLm were constructed that contained restriction enzyme sites NheI, ClaI and antibody constant domain. Mammalian expression vector pcDNA3-CHm contains IgG heavy-chain (HC) constant region and glycosylphosphatidylinositol anchor (GPI) that could be anchored full-length antibodies on the surface of mammalian cells. GOLPH2 prokaryotic expression vector was carried out in Escherichia coli and purified by immobilized metal affinity chromatography. Variable domain of heavy-chain and variable domain of light-chain genes were respectively inserted into the vector pcDNA3-CHm and pcDNA3-CLm by ligation, and antibody libraries are displayed as whole IgG molecules on the cell surface by co-transfecting this HC-GPI with a light chain. By screening the cell library using magnetic beads and cell ELISA, the cell clone that displayed GOLPH2-specific antibodies on cell surfaces was identified. The mammalian cell-based antibody display library is a great potential application for displaying full-length functional antibodies of targeting hepatocellular carcinoma on the surface of mammalian cells. Anti-GOLPH2 display antibody was successfully isolated from the library.

  10. Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency

    PubMed Central

    Yuan, Lin; Chi, Yayun; Chen, Weixiang; Chen, Xiaochen; Wei, Ping; Sheng, Weiqi; Zhou, Xiaoyan; Shi, Daren

    2015-01-01

    Mismatch repair defective (MMRd) colorectal carcinoma (CRC) is a distinct molecular phenotype of colorectal cancer, including 12% of sporadic CRC and 3% of Lynch Syndrome. In order to investigate the clinicopathological characteristics of MMRd colorectal carcinoma, and to find the most effective method for preliminary screening, 296 CRC fulfilled revised Bethesda Guideline (RB) were selected from 1450 CRCs to perform both IHC staining for MLH1, MSH2, MSH6, PMS2 and MSI analysis. Sixty-eight tumors were classified as MSI-H by MSI test. Colorectal carcinomas with MSI-H were prone to be proximal located, poorly differentiated, and relatively early staged, with infrequent metastasis to lymph node as well as to distant organs, compared with MSS ones. All of the 68 MMRd CRCs presented abnormal expression of at least one mismatch repair protein (MMRP), with 48 concurrent negative of MLH1 and PMS2, 14 concurrent negative of MSH2 and MSH6, 4 isolated negative of MSH6, 1 isolated negative of PMS2, and 1 concurrent negative of 4 MMRPs. All of the MLH1 negative tumors also showed abnormal expression of PMS2. All of the MSH2 negative cases also presented negative expression of MSH6. The sensitivity and specificity of the 2-antibody IHC test contained only PMS2 and MSH6 for screening for MMRd CRC were 100% and 98.2% respectively, exactly the same as that of the 4-antibody IHC test with all of the 4 MMRPs. The diagnostic accordance rate of the 2-antibody approach and MSI analysis was 98.6%. In conclusion, MMRd CRC has characteristic clinicopathological features different from MSS CRCs. The 2-antibody IHC approach containing MSH6 and PMS2 is the most easy and effective way to detecting MMR deficiency in CRC. PMID:26885030

  11. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells.

    PubMed

    Matthew, Elizabeth M; Zhou, Lanlan; Yang, Zhaohai; Dicker, David T; Holder, Sheldon L; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J; Lamparella, Nicholas E; Truica, Cristina I; El-Deiry, Wafik S

    2016-01-26

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing.

  12. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells

    PubMed Central

    Yang, Zhaohai; Dicker, David T.; Holder, Sheldon L.; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J.; Lamparella, Nicholas E.; Truica, Cristina I.; El-Deiry, Wafik S.

    2016-01-01

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing. PMID:26695546

  13. Systematic review of catheter-based intra-arterial therapies in hepatocellular carcinoma: state of the art and future directions

    PubMed Central

    Duran, R; Chapiro, J; Schernthaner, R E

    2015-01-01

    Intra-arterial therapies (IATs) play a pivotal role in the management of patients with primary and secondary liver malignancies. The unique advantages of these treatments are their ability to selectively deliver a high dose of anticancer treatment while preserving healthy liver tissue. The proven efficacy of these catheter-based locoregional therapies in a highly systemic chemoresistant cancer such as hepatocellular carcinoma (HCC), along with the minimally invasive nature of these treatments, quickly yielded wide acceptance in the medical community and revolutionized the field of Interventional Oncology. In this article, we describe the clinical rationale and background of catheter-based IATs. We provide an overview of clinical achievements of these treatments alone and in combination with sorafenib in patients with HCC. PMID:25978585

  14. Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

    PubMed Central

    Markwell, Steven M.; Weed, Scott A.

    2015-01-01

    Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment. PMID:25734659

  15. Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma

    PubMed Central

    Han, Yuewen; Niu, Jun; Wang, Dong; Li, Yuanyuan

    2016-01-01

    Epidemiological studies have validated the association between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). An increasing number of studies show that protein-protein interactions (PPIs) between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment. PMID:27115606

  16. Automatic classification of hepatocellular carcinoma images based on nuclear and structural features

    NASA Astrophysics Data System (ADS)

    Kiyuna, Tomoharu; Saito, Akira; Marugame, Atsushi; Yamashita, Yoshiko; Ogura, Maki; Cosatto, Eric; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2013-03-01

    Diagnosis of hepatocellular carcinoma (HCC) on the basis of digital images is a challenging problem because, unlike gastrointestinal carcinoma, strong structural and morphological features are limited and sometimes absent from HCC images. In this study, we describe the classification of HCC images using statistical distributions of features obtained from image analysis of cell nuclei and hepatic trabeculae. Images of 130 hematoxylin-eosin (HE) stained histologic slides were captured at 20X by a slide scanner (Nanozoomer, Hamamatsu Photonics, Japan) and 1112 regions of interest (ROI) images were extracted for classification (551 negatives and 561 positives, including 113 well-differentiated positives). For a single nucleus, the following features were computed: area, perimeter, circularity, ellipticity, long and short axes of elliptic fit, contour complexity and gray level cooccurrence matrix (GLCM) texture features (angular second moment, contrast, homogeneity and entropy). In addition, distributions of nuclear density and hepatic trabecula thickness within an ROI were also extracted. To represent an ROI, statistical distributions (mean, standard deviation and percentiles) of these features were used. In total, 78 features were extracted for each ROI and a support vector machine (SVM) was trained to classify negative and positive ROIs. Experimental results using 5-fold cross validation show 90% sensitivity for an 87.8% specificity. The use of statistical distributions over a relatively large area makes the HCC classifier robust to occasional failures in the extraction of nuclear or hepatic trabecula features, thus providing stability to the system.

  17. Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma.

    PubMed

    Han, Yuewen; Niu, Jun; Wang, Dong; Li, Yuanyuan

    2016-01-01

    Epidemiological studies have validated the association between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). An increasing number of studies show that protein-protein interactions (PPIs) between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment. PMID:27115606

  18. Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas.

    PubMed

    Schultheis, Anne M; Ng, Charlotte K Y; De Filippo, Maria R; Piscuoglio, Salvatore; Macedo, Gabriel S; Gatius, Sonia; Perez Mies, Belen; Soslow, Robert A; Lim, Raymond S; Viale, Agnes; Huberman, Kety H; Palacios, Jose C; Reis-Filho, Jorge S; Matias-Guiu, Xavier; Weigelt, Britta

    2016-06-01

    Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other. PMID:26832770

  19. A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells

    PubMed Central

    2013-01-01

    Background Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumor cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies. Methods Expression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74). Results Positive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC. EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity. Conclusions The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. Further prospective trials

  20. Extensive ameloblastic fibroma of the mandibula in a female adult patient: A case report with a follow-up of 3 years.

    PubMed

    Tozoglu, Sinan; Hatipoglu, Mukerrem; Aytekin, Zeliha; Gurer, Elif Inanc

    2016-01-01

    Ameloblastic fibroma (AF) is rare benign odontogenic tumour which usually occurs in the first two decades of life. It can occur either the mandible or maxilla but it is most frequently found in the posterior region of the mandible. Treatment of AF in usual is a conservative approach, such as enucleation and curettage but the aggressive lesions require a radical approach. A more radical approach should be considered in older patients who have likely high recurrence tendency. This report describes a case of AF in a 38-year-old female patient identified during a routine radiographic exam. Tomographic examination through three-dimensional reconstruction indicated vestibular fenestration of the cortical bone, with involvement of lingual cortical bone as the lession extended to the posterior region. We removed the tumor under local anesthesia. In this case patient has continued to be followed frequently and has been disease-free for 3 years.

  1. Extensive ameloblastic fibroma of the mandibula in a female adult patient: A case report with a follow-up of 3 years

    PubMed Central

    Tozoglu, Sinan; Hatipoglu, Mukerrem; Aytekin, Zeliha; Gurer, Elif Inanc

    2016-01-01

    Ameloblastic fibroma (AF) is rare benign odontogenic tumour which usually occurs in the first two decades of life. It can occur either the mandible or maxilla but it is most frequently found in the posterior region of the mandible. Treatment of AF in usual is a conservative approach, such as enucleation and curettage but the aggressive lesions require a radical approach. A more radical approach should be considered in older patients who have likely high recurrence tendency. This report describes a case of AF in a 38-year-old female patient identified during a routine radiographic exam. Tomographic examination through three-dimensional reconstruction indicated vestibular fenestration of the cortical bone, with involvement of lingual cortical bone as the lession extended to the posterior region. We removed the tumor under local anesthesia. In this case patient has continued to be followed frequently and has been disease-free for 3 years. PMID:27011753

  2. Genetic Variation in CXCL12 and Risk of Cervical Carcinoma: a Population-Based Case-Control Study

    PubMed Central

    Maley, Stephen N.; Schwartz, Stephen M.; Johnson, Lisa G.; Malkki, Mari; Du, Qin; Daling, Janet R.; Li, Shuying Sue; Zhao, Lue Ping; Petersdorf, Effie W.; Madeleine, Margaret M.

    2009-01-01

    Summary CXCL12 provides a chemotactic signal directing leukocyte migration and regulates metastatic behavior of tumor cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 (single SNP alleles and haplotypes) is associated with the risk of cervical carcinoma. Cases (N=917) were women diagnosed with invasive squamous cell cervical carcinoma (SCC), adenocarcinoma or adenosquamous carcinoma or adenocarcinoma in situ (ACIS) of the cervix, while residents of western Washington State. Control participants (N=849) were identified from the source population by random digit telephone dialing and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR=0.74, 95% C.I. 0.56–0.98). Among the ten common haplotypes inferred from the 9 tagSNPs, one haplotype defined by minor alleles at 5’ flanking SNP rs17885289 and rs266085, and common alleles at the other 7 SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR=0.72, 95% C.I. 0.56–0.93; recessive model OR=0.35, 95% C.I. 0.12–0.97; and log additive model OR=0.72, 95% C.I. 0.57–0.90). A stepwise procedure identified rs17885289, rs266085, and 3’ UTR SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3’ UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk. PMID:19788587

  3. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  4. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

    PubMed

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    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 (p<0.001) compared to BCC tissue group. Histopathology indicated that these differences partially arise from BCC-related characteristic changes in tissue morphology. Wilks lambda statistics demonstrated the potential of all investigated polarimetric properties for computer assisted classification of the two tissue groups. Based on differences in polarimetric properties, partial least square (PLS) regression classified the samples with 100% accuracy, sensitivity and specificity. These findings indicate that optical polarimetry together with PLS statistics hold promise for automated pathology classification. PMID:27083851

  5. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

    NASA Astrophysics Data System (ADS)

    Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

    To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

  6. Effect of colchicine on the transport of precursor enamel protein in secretory ameloblasts studied by /sup 3/H-proline radioautography in vitro

    SciTech Connect

    Matsuo, S.; Takano, Y.; Wakisaka, S.; Ichikawa, H.; Nishikawa, S.; Akai, M.

    1988-08-01

    The incorporation of 3H-proline into the secretory ameloblasts of rat molar tooth germs cultured with or without colchicine was studied by light and electron microscope radioautography to determine the function of microtubules in the transport of precursor enamel protein from the rough-surfaced endoplasmic reticulum (rER) to the Golgi cisternae. The grain counts over the transitional vesicles, which accumulated in various cellular regions with colchicine treatment, continued to increase with chase time, unlike in controls. At 30 and 90 min chase, these counts were significantly higher than in controls. Moreover, the total grain count over the organelles (rER, pale granules, and transitional vesicles), which are positioned before the Golgi cisternae in the synthetic pathway, maintained a significantly higher level at 90 min chase in colchicine-treated tooth germs than in controls. The transport of synthesized protein to the Golgi cisternae via transitional vesicles was suppressed in colchicine-treated tooth germs. Some grains appeared with time over pale granular materials that appeared in the intercellular spaces of secretory ameloblasts with colchicine treatment. However, at each chase period, the grain count over pale granular materials was not so high as the count over the enamel in control. The present results indicate that colchicine affects the transport of newly synthesized protein from the rER to the Golgi cisterna via transitional vesicles, probably by interfering with the oriented transport related to microtubular function. It is suggested that the microtubular system may be concerned with the movement of the transitional vesicles.

  7. Adrenocortical carcinoma

    MedlinePlus

    ... this tumor. Adrenocortical carcinoma can produce the hormones cortisol, aldosterone, estrogen, or testosterone, as well as other ... Symptoms of increased cortisol or other adrenal gland hormones: ... high on the back just below the neck ( buffalo hump ) Flushed, ...

  8. Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset.

    PubMed

    Wang, Lishan; Zang, Weidong; Xie, Dongli; Ji, Weidong; Pan, Yaosheng; Li, Zhiqiang; Shen, Jiawei; Shi, Yongyong

    2013-06-01

    Liver carcinomas have been classified into three types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC). We aim to find the common and different characteristic of these three types of liver cancer. The gene expression profiling of HCC, CC, and CHC were compared with each other, and enrichment pathways and processes in these three liver cancers were also identified. Using GSE15765 datasets downloaded from NCBI GEO database, the gene expression profiling of HCC, CC, and CHC were compared with each other (HCC compared with CC, HCC compared with CHC, and CC compared with HCC). Then, the differentially expressed genes (DEGs) were identified in these three groups respectively, and three PPI networks were constructed for DEGs in each group. Subsequently, the clusters in these networks were identified and further analyzed by ClusterONE and MCODE. Finally, gene set enrichment analysis enrichment analysis was performed to illustrate altered pathways and processes for each type of liver cancer. A total of 112, 530, and 64 DEGs were identified in three groups, respectively, and three PPI networks were constructed respectively for the corresponding group. Through the cluster analysis, we found some new differential marker genes for distinguishing the difference between these three types of liver cancer. We also indicated that we can distinguish HCC with CC through altered pathways and processes. Our findings develop new biomarkers for categorizing the primary liver cancer and may improve patient prognosis of these cancers. However, further validation is required since our results were based on microarray data derived from a small sample size.

  9. Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database

    PubMed Central

    Li, Jun-Jing; Song, Chuan-Gui; Shao, Zhi-Ming

    2016-01-01

    Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. Our study was designed to identify difference in characteristics and outcomes between MBC and invasive ductal carcinoma (IDC), and further confirm the prognostic factors of MBC. Utilizing Surveillance, Epidemiology, and End Results (SEER), we identified 84,764 eligible patients, including 309 MBC and 84,455 IDC. Compared with the IDC group, the MBC group was associated with younger age at diagnosis, higher grade, more advanced stage, larger tumor size, and higher proportion of triple-negative breast cancer (TNBC). Kaplan-Meier analysis and univariate Cox proportional hazard regression model showed that patients with IDC had significantly better breast cancer-specific survival (BCSS) compared to MBC, but they had similar overall survival (OS). However, MBC histology was no longer a surrogate for worse BCSS or OS after 1:1 matching by age, American Joint Committee on Cancer (AJCC) stage, grade and breast subtype. In addition, it was exposed that not married status, high grade, large tumor size, positive nodal status, the subtype of TNBC and no receipt of radiation therapy were significantly associated with poor BCSS and OS. In conclusion, MBC demonstrated more aggressive behavior but similar outcomes compared to IDC, which may be determined by prognostic factors such as breast subtype. These results not only confer deeper insight into MBC but contribute to individualized and tailored therapy, and thereby may improve clinical management and outcomes. PMID:27009810

  10. Diagnosis of Ovarian Carcinoma Histotype Based on Limited Sampling: A Prospective Study Comparing Cytology, Frozen Section, and Core Biopsies to Full Pathologic Examination.

    PubMed

    Hoang, Lien N; Zachara, Susanna; Soma, Anita; Köbel, Martin; Lee, Cheng-Han; McAlpine, Jessica N; Huntsman, David; Thomson, Thomas; van Niekerk, Dirk; Singh, Naveena; Gilks, C Blake

    2015-11-01

    Growing insights into the biological features and molecular underpinnings of ovarian cancer has prompted a shift toward histotype-specific treatments and clinical trials. As a result, the preoperative diagnosis of ovarian carcinomas based on small tissue sampling is rapidly gaining importance. The data on the accuracy of ovarian carcinoma histotype-specific diagnosis based on small tissue samples, however, remains very limited in the literature. Herein, we describe a prospective series of 30 ovarian tumors diagnosed using cytology, frozen section, core needle biopsy, and immunohistochemistry (p53, p16, WT1, HNF-1β, ARID1A, TFF3, vimentin, and PR). The accuracy of histotype diagnosis using each of these modalities was 52%, 81%, 85%, and 84% respectively, using the final pathology report as the reference standard. The accuracy of histotype diagnosis using the Calculator for Ovarian Subtype Prediction (COSP), which evaluates immunohistochemical stains independent of histopathologic features, was 85%. Diagnostic accuracy varied across histotype and was lowest for endometrioid carcinoma across all diagnostic modalities (54%). High-grade serous carcinomas were the most overdiagnosed on core needle biopsy (accounting for 45% of misdiagnoses) and clear cell carcinomas the most overdiagnosed on frozen section (accounting for 36% of misdiagnoses). On core needle biopsy, 2/30 (7%) cases had a higher grade lesion missed due to sampling limitations. In this study, we identify several challenges in the diagnosis of ovarian tumors based on limited tissue sampling. Recognition of these scenarios can help improve diagnostic accuracy as we move forward with histotype-specific therapeutic strategies.

  11. Adenoid cystic carcinoma of the trachea treated with PET-CT based intensity modulated radiotherapy.

    PubMed

    Haresh, Kunhi Parambath; Prabhakar, Ramachandran; Rath, Goura K; Sharma, Daya Nand; Julka, Pramod K; Subramani, V

    2008-07-01

    Primary tumors of the trachea are rare and are usually malignant in adults and benign in children. Adenoid cystic carcinoma, which is of salivary gland origin, account for about one thirds of adult primary tracheal tumors. A 49-year-old gentleman presented to us after undergoing a pneumonectomy elsewhere. Computed tomography scan of the thorax at our hospital showed a residual disease in the primary site, size of which was same as that in the preoperative scan. Because there was a compromised respiratory reserve due to pneumonectomy we decided to keep the radiation dose to the remaining lung as low as possible. We treated him by positron emission tomography-computed tomography (PET-CT) directed intensity modulated radiation therapy to a dose of 60 Gy in 30 Fractions over 6 weeks on a linear accelerator. PET helped in exact localization of the target on the planning CT. He tolerated the treatment very well. PET-CT done 1 year posttreatment showed no residual disease. Presently he is disease free with good pulmonary reserve. PMID:18594327

  12. Nuclear magnetic resonance-based study reveals the metabolomics profile of nasopharyngeal carcinoma.

    PubMed

    Wang, Y; Luo, X; Zhang, G H; Li, S L

    2016-01-01

    Proton nuclear magnetic resonance ([(1)H]-NMR) spectroscopy has been used to investigate metabolites in serum and several types of tissue. We used NMR spectroscopy to explore the differential metabolic profiles in serum from nasopharyngeal carcinoma (NPC) patients. Moreover, metabolites with potential as biomarkers for identifying NPC patients were primarily identified. Serum samples were collected from 40 enrolled participants comprising 20 healthy subjects and 20 NPC patients. Samples were analyzed using a 600-MHz NMR spectrometer. The [(1)H]-NMR spectra were further analyzed with partial least squares-discriminant analysis for screening differential metabolites. NMR spectroscopy identified a total of eight metabolites that were present at different levels when the sera of NPC patients were compared with those of healthy individuals. Methionine, taurine (P < 0.05), and choline-like metabolites (P < 0.05) were mostly elevated in the sera of NPC patients. In contrast, the levels of lipids (P < 0.01), isoleucine (P < 0.05), unsaturated lipids (P < 0.01), trimethylamine oxidase (P < 0.05), and carbohydrates (P < 0.05) were lower in the sera of the NPC patients than in the healthy controls. We explored the differential metabolic profiles in sera from NPC patients. [(1)H]-NMR spectroscopy can be used to identify specific metabolites, and is capable of distinguishing between NPC patients and healthy individuals. PMID:27323073

  13. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma

    PubMed Central

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L.; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

  14. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  15. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma.

    PubMed

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

  16. Nonfunctional parathyroid carcinoma.

    PubMed Central

    Giessler, G. A.; Beech, D. J.

    2001-01-01

    Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with elevated serum levels of parathormone and calcium. These tumors may also be nonfunctional. Clinical detection of nonfunctioning parathyroid malignancies preoperatively is primarily based on symptoms of an expanding neck mass. This ominous complaint is typically accompanied with an advanced stage of the disease at initial diagnosis. Because there is a paucity of data in the literature regarding nonfunctioning parathyroid carcinoma, prognosis can not be readily assessed. In both functional and nonfunctional parathyroid carcinoma, early surgery has proven to be the only curative treatment approach whereas both chemotherapy and radiation therapy fail to produce systemic or regional benefit when used alone. Hence, parathyroid cancer should be considered in every patient evaluated for a neck mass regardless of the blood calcium and blood parathormone level. PMID:11491274

  17. The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically

  18. Tissue microarray-based study of hepatocellular carcinoma validating SPIB as potential clinical prognostic marker.

    PubMed

    Ho, Yi-Jung; Lin, Yueh-Min; Huang, Yen-Chi; Yeh, Kun-Tu; Lin, Liang-In; Lu, Jeng-Wei

    2016-01-01

    Currently, the prognostic significance of SPIB protein overexpression in human hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the level of SPIB expression in human HCC in order to determine possible correlations between SPIB expression and clinicopathological findings. The expression of SPIB proteins was detected using immunohistochemical staining in commercial multiple-tissue microarrays as a means of examining expression profiles in patients. Using online biomarker validation tool SurvExpress, we focused on the correlation between SPIB overexpression and survival as well as relapse-free survival (RFS). Results show that SPIB protein expression levels were significantly higher in colon, liver, and stomach tumors than in non-tumor tissues (p<0.05). SPIB overexpression in patients with HCC was also significantly higher than that of the normal samples (p<0.001). Among patients with liver disease, SPIB protein expression levels differ significantly according to the stage of liver disease, specifically between stages I, II, and III of HCC (p<0.05). SPIB expression was also shown to be significantly correlated with age (p=0.046) and histological grade (p=0.027). Furthermore, the SurvExpress analysis suggested that high SPIB and KI-67 mRNA expression were significantly associated with the poor survival of patients with HCC (p<0.05). Our results indicate that cross-talk in the expression of SPIB and KI-67 may be associated with poor prognosis and may potentially serve as a clinical prognostic indicator of HCC. This is the first time that such an association has been reported. PMID:26610895

  19. Characterization of hepatocellular carcinoma cell lines based on cell adhesion molecules.

    PubMed

    Jung, Cheol Woong; Song, Tae-Jin; Lee, Kun-Ok; Choi, Sae Byeol; Kim, Wan Bae; Suh, Sung Ock; Kim, Young Chul; Choi, Sang Yong

    2012-06-01

    Many studies which focus on the molecules and mechanisms related to the characteristics of the cancer have been performed. In particular, cell adhesion molecules (CAMs) are known to play a central role in the adhesion of cancer cells to vascular endothelial cells. In this study, the expression of CAMs in hepatocellular carcinoma (HCC) cell lines was analyzed and correlated with the characteristics of various HCC cell lines. Eight human HCC cell lines were used in this study. We analyzed the expression of ICAM-1, E-selectin and the integrin subunits of HCC cell lines by western blot analysis and ELISA kit. We estimated the expression of integrin-α5 using western blot analysis and RT-PCR to compare the expression at the gene level with the protein level. In addition, we determined the expression of TGF-β1, as one of the markers for the cellular activity compared to the levels of expression with the expression of integrin-α3 and -α5. ICAM-1 was highly expressed in all of the cell lines except SNU398 and Hep3B, which exhibit a more aggressive nature among the studied HCC cell lines. E-selectin and integrin subunits varied in all HCC cell lines. In particular, integrin-β2 was highly expressed on all HCC cell lines. In conclusion, the levels of expression of the CAMs may not affect cellular activity, morphology or tumorigenicity. However, most HCC cell lines show various expressions of CAMs, suggesting that HCC cell lines expressing the major CAMs remain candidates for molecular targeted therapy, which may need to be patient-tailored for therapy according to the molecular profile.

  20. New malignancies after squamous cell carcinoma and melanomas: a population-based study from Norway

    PubMed Central

    2014-01-01

    Background Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers. Methods All invasive cutaneous malignant melanomas (CMM, N = 28 069) and squamous cell carcinomas (SCC, N = 24 620) diagnosed in Norway during 1955–2008 were included. Rates of new primary cancers in skin cancer survivors were compared to rates of primary malignancies in the general population using standardized incidence ratios (SIR). Discrete-time logistic regression models were applied to individual-level data to estimate cancer risk among those with and without a prior skin cancer, accounting for residential region, education, income, parenthood, marital status and parental cancer status, using a 20% random sample of the entire Norwegian population as reference. Further analyses of the skin cancer cohort were undertaken to determine risk factors related to subsequent cancers. Results During follow-up, 9608 new primary cancers occurred after an initial skin cancer. SIR analyses showed 50% and 90% increased risks for any cancer after CMM and SCC, respectively (p < 0.01). The logistic regression model suggested even stronger increase after SCC (130%). The highest risk was seen for subsequent skin cancers, but several non-skin cancers were also diagnosed in excess: oral, lung, colon, breast, prostate, thyroid, leukemia, lymphoma and central nervous system. Factors that were associated with increased risk of subsequent cancers include male sex, older age, lower residential latitude, being married and low education and income. Parental cancer did not increase the risk of a subsequent cancer after SCC, but was a significant predictor among younger CMM survivors. Conclusions Our results provide information on shared environmental and genetic risk factors for first and

  1. 1H nuclear magnetic resonance-based extracellular metabolomic analysis of multidrug resistant Tca8113 oral squamous carcinoma cells

    PubMed Central

    WANG, HUI; CHEN, JIAO; FENG, YUN; ZHOU, WENJIE; ZHANG, JIHUA; YU, YU; WANG, XIAOQIAN; ZHANG, PING

    2015-01-01

    A major obstacle of successful chemotherapy is the development of multidrug resistance (MDR) in the cancer cells, which is difficult to reverse. Metabolomic analysis, an emerging approach that has been increasingly applied in various fields, is able to reflect the unique chemical fingerprints of specific cellular processes in an organism. The assessment of such metabolite changes can be used to identify novel therapeutic biomarkers. In the present study, 1H nuclear magnetic resonance (NMR) spectroscopy was used to analyze the extracellular metabolomic spectrum of the Tca8113 oral squamous carcinoma cell line, in which MDR was induced using the carboplatin (CBP) and pingyangmycin (PYM) chemotherapy drugs in vitro. The data were analyzed using the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) methods. The results demonstrated that the extracellular metabolomic spectrum of metabolites such as glutamate, glycerophosphoethanol amine, α-Glucose and β-Glucose for the drug-induced Tca8113 cells was significantly different from the parental Tca8113 cell line. A number of biochemicals were also significantly different between the groups based on their NMR spectra, with drug-resistant cells presenting relatively higher levels of acetate and lower levels of lactate. In addition, a significantly higher peak was observed at δ 3.35 ppm in the spectrum of the PYM-induced Tca8113 cells. Therefore, 1H NMR-based metabolomic analysis has a high potential for monitoring the formation of MDR during clinical tumor chemotherapy in the future. PMID:26137105

  2. Aptamer-based Sandwich Assay and its Clinical Outlooks for Detecting Lipocalin-2 in Hepatocellular Carcinoma (HCC)

    PubMed Central

    Lee, Kyeong-Ah; Ahn, Ji-Young; Lee, Sang-Hee; Singh Sekhon, Simranjeet; Kim, Dae-Ghon; Min, Jiho; Kim, Yang-Hoon

    2015-01-01

    We validated a single-stranded, DNA aptamer-based, diagnostic method capable of detecting Lipocalin-2 (LCN2), a biomarker from clinically relevant hepatocellular carcinoma (HCC) patient serum, in the sandwich assay format. Nine aptamers (LCN2_apta1 to LCN2_apta9) for LCN2 were screened with SELEX processes, and a sandwich pair (LCN2_apta2 and LCN2_apta4) was finally chosen using surface plasmon resonance (SPR) and dot blotting analysis. The result of the proposed aptamer sandwich construction shows that LCN2 was sensitively detected in the concentration range of 2.5–500 ng mL−1 with a limit of detection of 0.6 ng mL−1. Quantitative measurement tests in HCC patients were run on straight serum and were compared with the performance of the conventional antibody-based ELISA kit. The aptamer sandwich assay demonstrated an excellent dynamic range for LCN2 at clinically relevant serum levels, covering sub-nanogram per mL concentrations. The new approach offers a simple and robust method for detecting serum biomarkers that have low and moderate abundance. It consists of functionalization, hybridization and signal read-out, and no dilution is required. The results of the study demonstrate the capability of the aptamer sandwich assay platform for diagnosing HCC and its potential applicability to the point-of-care testing (POCT) system. PMID:26039737

  3. [Thymic carcinomas].

    PubMed

    Ströbel, P; Weis, C-A; Marx, A

    2016-09-01

    Thymic carcinomas (TC) are approximately 10 times less prevalent than thymomas but of high clinical relevance because they are more aggressive, less frequently resectable than thymomas and usually refractory to classical and targeted long-term treatment approaches. Furthermore, in children and adolescents TC are more frequent than thymomas and particularly in this age group, germ cell tumors need to be a differential diagnostic consideration. In diagnostic terms pathologists face two challenges: a), the distinction between thymic carcinomas and thymomas with a similar appearance and b), the distinction between TC and histologically similar metastases and tumor extensions from other primary tumors. Overcoming these diagnostic challenges is the focus of the new WHO classification of thymic epithelial tumors. The objectives of this review are to highlight novel aspects of the WHO classification of thymic carcinomas and to address therapeutically relevant diagnostic pitfalls. PMID:27538748

  4. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

    PubMed Central

    Atzpodien, J; Schmitt, E; Gertenbach, U; Fornara, P; Heynemann, H; Maskow, A; Ecke, M; Wöltjen, H H; Jentsch, H; Wieland, W; Wandert, T; Reitz, M

    2005-01-01

    We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy. PMID:15756254

  5. Dosimetric study for cervix carcinoma treatment using intensity modulated radiation therapy (IMRT) compensation based on 3D intracavitary brachytherapy technique

    PubMed Central

    Yin, Gang; Wang, Pei; Lang, Jinyi; Tian, Yin; Luo, Yangkun; Fan, Zixuan

    2016-01-01

    Purpose Intensity modulated radiation therapy (IMRT) compensation based on 3D high-dose-rate (HDR) intracavitary brachytherapy (ICBT) boost technique (ICBT + IMRT) has been used in our hospital for advanced cervix carcinoma patients. The purpose of this study was to compare the dosimetric results of the four different boost techniques (the conventional 2D HDR intracavitary brachytherapy [CICBT], 3D optimized HDR intracavitary brachytherapy [OICBT], and IMRT-alone with the applicator in situ). Material and methods For 30 patients with locally advanced cervical carcinoma, after the completion of external beam radiotherapy (EBRT) for whole pelvic irradiation 45 Gy/25 fractions, five fractions of ICBT + IMRT boost with 6 Gy/fractions for high risk clinical target volume (HRCTV), and 5 Gy/fractions for intermediate risk clinical target volume (IRCTV) were applied. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired using an in situ CT/MRI-compatible applicator. The gross tumor volume (GTV), the high/intermediate-risk clinical target volume (HRCTV/IRCTV), bladder, rectum, and sigmoid were contoured by CT scans. Results For ICBT + IMRT plan, values of D90, D100 of HRCTV, D90, D100, and V100 of IRCTV significantly increased (p < 0.05) in comparison to OICBT and CICBT. The D2cc values for bladder, rectum, and sigmoid were significantly lower than that of CICBT and IMRT alone. In all patients, the mean rectum V60 Gy values generated from ICBT + IMRT and OICBT techniques were very similar but for bladder and sigmoid, the V60 Gy values generated from ICBT + IMRT were higher than that of OICBT. For the ICBT + IMRT plan, the standard deviations (SD) of D90 and D2cc were found to be lower than other three treatment plans. Conclusions The ICBT + IMRT technique not only provides good target coverage but also maintains low doses (D2cc) to the OAR. ICBT + IMRT is an optional technique to boost parametrial region or tumor of large size and irregular shape

  6. Investigation of Pokemon-regulated proteins in hepatocellular carcinoma using mass spectrometry-based multiplex quantitative proteomics.

    PubMed

    Bi, Xin; Jin, Yibao; Gao, Xiang; Liu, Feng; Gao, Dan; Jiang, Yuyang; Liu, Hongxia

    2013-01-01

    Pokemon is a transcription regulator involved in embryonic development, cellular differentiation and oncogenesis. It is aberrantly overexpressed in multiple human cancers including Hepatocellular carcinoma (HCC) and is considered as a promising biomarker for HCC. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy was used to investigate the proteomic profile associated with Pokemon in human HCC cell line QGY7703 and human hepatocyte line HL7702. Samples were labeled with four-plex iTRAQ reagents followed by two-dimensional liquid chromatography coupled with tandem mass spectrometry analysis. A total of 24 differentially expressed proteins were selected as significant. Nine proteins were potentially up-regulated by Pokemon while 15 proteins were potentially down-regulated and many proteins were previously identified as potential biomarkers for HCC. Gene ontology (GO) term enrichment revealed that the listed proteins were mainly involved in DNA metabolism and biosynthesis process. The changes of glucose-6-phosphate 1-dehydrogenase (G6PD, up-regulated) and ribonucleoside-diphosphate reductase large sub-unit (RIM1, down-regulated) were validated by Western blotting analysis and denoted as Pokemon's function of oncogenesis. We also found that Pokemon potentially repressed the expression of highly clustered proteins (MCM3, MCM5, MCM6, MCM7) which played key roles in promoting DNA replication. Altogether, our results may help better understand the role of Pokemon in HCC and promote the clinical applications. PMID:24261083

  7. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma.

    PubMed

    Wu, Yishuo; Zhang, Ning; Li, Kaiwen; Chen, Haitao; Lin, Xiaolin; Yu, Yang; Gou, Yuancheng; Hou, Jiangang; Jiang, Deke; Na, Rong; Wang, Xiang; Ding, Qiang; Xu, Jianfeng

    2016-04-01

    The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10(-7)). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10(-10)). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available.

  8. iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma

    PubMed Central

    Zhang, Yushi; Cai, Yi; Yu, Hongyan; Li, Hanzhong

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC. PMID:26425554

  9. Investigation of Pokemon-regulated proteins in hepatocellular carcinoma using mass spectrometry-based multiplex quantitative proteomics.

    PubMed

    Bi, Xin; Jin, Yibao; Gao, Xiang; Liu, Feng; Gao, Dan; Jiang, Yuyang; Liu, Hongxia

    2013-01-01

    Pokemon is a transcription regulator involved in embryonic development, cellular differentiation and oncogenesis. It is aberrantly overexpressed in multiple human cancers including Hepatocellular carcinoma (HCC) and is considered as a promising biomarker for HCC. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy was used to investigate the proteomic profile associated with Pokemon in human HCC cell line QGY7703 and human hepatocyte line HL7702. Samples were labeled with four-plex iTRAQ reagents followed by two-dimensional liquid chromatography coupled with tandem mass spectrometry analysis. A total of 24 differentially expressed proteins were selected as significant. Nine proteins were potentially up-regulated by Pokemon while 15 proteins were potentially down-regulated and many proteins were previously identified as potential biomarkers for HCC. Gene ontology (GO) term enrichment revealed that the listed proteins were mainly involved in DNA metabolism and biosynthesis process. The changes of glucose-6-phosphate 1-dehydrogenase (G6PD, up-regulated) and ribonucleoside-diphosphate reductase large sub-unit (RIM1, down-regulated) were validated by Western blotting analysis and denoted as Pokemon's function of oncogenesis. We also found that Pokemon potentially repressed the expression of highly clustered proteins (MCM3, MCM5, MCM6, MCM7) which played key roles in promoting DNA replication. Altogether, our results may help better understand the role of Pokemon in HCC and promote the clinical applications.

  10. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection

    PubMed Central

    Fu, Yi-Peng; Ni, Xiao-Chun; Yi, Yong; Cai, Xiao-Yan; He, Hong-Wei; Wang, Jia-Xing; Lu, Zhu-Feng; Han, Xu; Cao, Ya; Zhou, Jian; Fan, Jia; Qiu, Shuang-Jian

    2016-01-01

    Abstract As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature. In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone. IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID:26886627

  11. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma

    PubMed Central

    Chen, Haitao; Lin, Xiaolin; Yu, Yang; Gou, Yuancheng; Hou, Jiangang; Jiang, Deke; Na, Rong; Wang, Xiang; Ding, Qiang; Xu, Jianfeng

    2016-01-01

    The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10−7). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10−10). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available. PMID:27229762

  12. Mass spectrometry-based analysis of rat liver and hepatocellular carcinoma Morris hepatoma 7777 plasma membrane proteome.

    PubMed

    Cao, Lulu; Clifton, James G; Reutter, Werner; Josic, Djuro

    2013-09-01

    The gel-based proteomic analysis of plasma membranes from rat liver and chemically induced, malignant hepatocellular carcinoma Morris hepatoma 7777 was systematically optimized to yield the maximum number of proteins containing transmembrane domains (TMDs). Incorporation of plasma membrane proteins into a polyacrylamide "tube gel" followed by in-gel digestion of "tube gel" pieces significantly improved detection by electrospray ionization-liquid chromatography-tandem mass spectrometry. Removal of less hydrophobic proteins by washing isolated plasma membranes with 0.1 M sodium carbonate enables detection of a higher number of hydrophobic proteins containing TMDs in both tissues. Subsequent treatment of plasma membranes by a proteolytic enzyme (trypsin) causes the loss of some of the proteins that are detected after washing with sodium carbonate, but it enables the detection of other hydrophobic proteins containing TMDs. Introduction of mass spectrometers with higher sensitivity, higher mass resolution and mass accuracy, and a faster scan rate significantly improved detection of membrane proteins, but the improved sample preparation is still useful and enables detection of additional hydrophobic proteins. Proteolytic predigestion of plasma membranes enables detection of additional hydrophobic proteins and better sequence coverage of TMD-containing proteins in plasma membranes from both tissues.

  13. A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma.

    PubMed

    Maillet, A; Yadav, S; Loo, Y L; Sachaphibulkij, K; Pervaiz, S

    2013-06-06

    Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an attractive avenue for novel drug discovery. Here, we report the anticancer activity of a novel Osmium-based organometallic compound (hereafter named Os) on different colorectal carcinoma cell lines. HCT116 cell line was highly sensitive to Os and displayed characteristic features of autophagy and apoptosis; however, inhibition of autophagy did not rescue cell death unlike the pan-caspase inhibitor z-VAD-fmk. Furthermore, Os significantly altered mitochondrial morphology, disrupted electron transport flux, decreased mitochondrial transmembrane potential and ATP levels, and triggered a significant increase in reactive oxygen species (ROS) production. Interestingly, the sensitivity of cell lines to Os was linked to its ability to induce mitochondrial ROS production (HCT116 and RKO) as HT29 and SW620 cell lines that failed to show an increase in ROS were resistant to the death-inducing activity of Os. Finally, intra-peritoneal injections of Os significantly inhibited tumor formation in a murine model of HCT116 carcinogenesis, and pretreatment with Os significantly enhanced tumor cell sensitivity to cisplatin and doxorubicin. These data highlight the mitochondria-targeting activity of this novel compound with potent anticancer effect in vitro and in vivo, which could have potential implications for strategic therapeutic drug design.

  14. Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

    PubMed

    Shao, Yaping; Zhu, Bin; Zheng, Ruiyin; Zhao, Xinjie; Yin, Peiyuan; Lu, Xin; Jiao, Binghua; Xu, Guowang; Yao, Zhenzhen

    2015-02-01

    Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.

  15. Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

    PubMed Central

    Topkan, Erkan; Yavuz, Ali A; Aydin, Mehmet; Onal, Cem; Yapar, Fuat; Yavuz, Melek N

    2008-01-01

    Background To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC). Methods Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs. Results Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs. Conclusion Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses. PMID:18808725

  16. Iron-Oxide-Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

    PubMed

    Wang, Kui; Kievit, Forrest M; Sham, Jonathan G; Jeon, Mike; Stephen, Zachary R; Bakthavatsalam, Arvind; Park, James O; Zhang, Miqin

    2016-01-27

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence-specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle-based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP-siRNA-GPC3 Ab) is made of an iron oxide core coated with chitosan-polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican-3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle-mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP-siLuc-GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC.

  17. Gold Nanorods Based Air Scanning Electron Microscopy and Diffusion Reflection Imaging for Mapping Tumor Margins in Squamous Cell Carcinoma.

    PubMed

    Ankri, Rinat; Ashkenazy, Ariel; Milstein, Yonat; Brami, Yaniv; Olshinka, Asaf; Goldenberg-Cohen, Nitza; Popovtzer, Aron; Fixler, Dror; Hirshberg, Abraham

    2016-02-23

    A critical challenge arising during a surgical procedure for tumor removal is the determination of tumor margins. Gold nanorods (GNRs) conjugated to epidermal growth factor receptors (EGFR) (GNRs-EGFR) have long been used in the detection of cancerous cells as the expression of EGFR dramatically increases once the tissue becomes cancerous. Optical techniques for the identification of these GNRs-EGFR in tumor are intensively developed based on the unique scattering and absorption properties of the GNRs. In this study, we investigate the distribution of the GNRs in tissue sections presenting squamous cell carcinoma (SCC) to evaluate the SCC margins. Air scanning electron microscopy (airSEM), a novel, high resolution microscopy is used, enabling to localize and actually visualize nanoparticles on the tissue. The airSEM pictures presented a gradient of GNRs from the tumor to normal epithelium, spread in an area of 1 mm, suggesting tumor margins of 1 mm. Diffusion reflection (DR) measurements, performed in a resolution of 1 mm, of human oral SCC have shown a clear difference between the DR profiles of the healthy epithelium and the tumor itself. PMID:26759920

  18. Carcinoma of the base of the tongue: results of radical irradiation with surgery reserved for irradiation failure

    SciTech Connect

    Parsons, J.T.; Million, R.R.; Cassisi, N.J.

    1982-06-01

    Between 1964 and 1977, 95 previously untreated patients with squamous cell carcinoma of the base of the tongue received treatment with curative intent at the University of Florida. Eighty-six of the 95 patients (91%) had Stage III or IV disease at presentation. Eighty-nine patients received radical courses of irradiation to the primary with or without neck dissection(s), with surgery reserved for salvage of irradiation failure. Six patients underwent planned combined treatment of the primary lesion. Of the 89 patients whose primary lesions were radically irradiated, failure at the primary site occurred in 24% of those with T1-3 lesions and 78% with T4 lesions. Control results were related to irradiation treatment technique. None of the 9 patients with Stage I-II disease died of the cancer. Actuarial survival at 5 years for Stage III patients was 46%. Within the Stage IV population there is a subgroup of patients with highly treatable and curable disease. The addition of a neck dissection following irradiation of N2-N3 neck disease decreased the incidence of failure in the neck. No patient developed severe soft tissue necrosis or required mandibulectomy for bone exposure following irradiation.

  19. Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature

    PubMed Central

    Huang, Po-Jung; Huang, Yi; Hsu, An; Tang, Petrus; Chang, Yu-Sun; Chen, Hua-Chien; Yen, Tzu-Chen

    2015-01-01

    Background Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Methods Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). Results We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Conclusions Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients. PMID:25980437

  20. A Retrospective Comparison of Taxane and Fluorouracil-based Chemoradiotherapy in Patients with Inoperable Esophageal Squamous Cell Carcinoma

    PubMed Central

    Sun, Xiaojiang; Han, Shuiyun; Gu, Feiying; Lin, Gang; Wang, Zhun; Wang, Yuezhen; Xu, Yaping

    2016-01-01

    Purpose: To retrospectively compare taxane-based with fluorouracil-based chemoradiotherapy in terms of toxicity profiles, efficacy and survival in patients with inoperable esophageal cancer. Methods and Materials: We analyzed retrospectively 179 consecutive patients who were unresectable or medically unfit for surgery between March 2009 and November 2014. Eight-three patients were included in the taxane group and 96 cases were in the fluorouracil group. Results: The overall response rate (ORR) in the taxane group was higher than fluorouracil group, but was not significantly different (71.6% vs. 63.5%, respectively, P=0.255). In total, 53.0% (44/83) of the patients in the taxane group had progressive disease versus 54.2% (52/96) in the fluorouracil group (not significantly different (P=0.758)). There was no significant difference in overall response rate, progression free survival and overall survival, as well as treatment-related death. In terms of non-hematological toxicity, patients in the taxane group experienced a lower incidence of ≥ grade 3 esophageal perforation or fistula (4.8% vs. 13.5%, P=0.047) and pneumonia (4.8% vs. 9.7%, P=0.242). Regarding hematological toxicity, thrombocytopenia in the taxane group was significantly lower (4.8% vs. 13.5%, P=0.047), but there was a trend towards a higher rate of ≥ grade 3 leukopenia (34.9% vs.26.0%, P=0.196). Conclusions: Chemoradiation with taxane-based regimens is well tolerated, with potentially promising efficacy, and could become a good alternative treatment in a first line setting for patients with inoperable esophageal squamous cell carcinoma. PMID:27326249

  1. Division of focal plane polarimeter-based 3 × 4 Mueller matrix microscope: a potential tool for quick diagnosis of human carcinoma tissues

    NASA Astrophysics Data System (ADS)

    Chang, Jintao; He, Honghui; Wang, Ye; Huang, Yi; Li, Xianpeng; He, Chao; Liao, Ran; Zeng, Nan; Liu, Shaoxiong; Ma, Hui

    2016-05-01

    A polarization microscope is a useful tool to reveal the optical anisotropic nature of a specimen and can provide abundant microstructural information about samples. We present a division of focal plane (DoFP) polarimeter-based polarization microscope capable of simultaneously measuring both the Stokes vector and the 3×4 Mueller matrix with an optimal polarization illumination scheme. The Mueller matrix images of unstained human carcinoma tissue slices show that the m24 and m34 elements can provide important information for pathological observations. The characteristic features of the m24 and m34 elements can be enhanced by polarization staining under illumination by a circularly polarized light. Hence, combined with a graphics processing unit acceleration algorithm, the DoFP polarization microscope is capable of real-time polarization imaging for potential quick clinical diagnoses of both standard and frozen slices of human carcinoma tissues.

  2. Selective killing of hepatocellular carcinoma HepG2 cells by three-dimensional nanographene nanoparticles based on triptycene

    NASA Astrophysics Data System (ADS)

    Xiong, Xiaoqin; Gan, Lu; Liu, Ying; Zhang, Chun; Yong, Tuying; Wang, Ziyi; Xu, Huibi; Yang, Xiangliang

    2015-03-01

    Carbon-based materials have been widely used in the biomedical fields including drug delivery and cancer therapies. In this paper, a recently synthesized three-dimensional nanographene (NG) based on triptycene self-assembles into nanoparticles which selectively kill human hepatocellular carcinoma HepG2 cells as compared to human normal liver HL7702 cells. Obvious differences in cellular accumulation, the endocytic pathway and intracellular trafficking of NG nanoparticles are observed in HepG2 cells and HL7702 cells. Further studies reveal that NG nanoparticles significantly increase the levels of reactive oxygen species (ROS) in HepG2 cells, but not in HL7702 cells. NG nanoparticle-induced ROS result in apoptosis induction and the decrease in mitochondrial membrane potential in HepG2 cells. Moreover, IKK/nuclear factor-κB (NF-κB) signaling is found to be activated by NG nanoparticle-induced ROS and serves to antagonize NG nanoparticle-induced apoptosis in HepG2 cells. Our studies show that the distinct behaviors of cellular uptake and ROS-mediated cytotoxicity are responsible for the selective killing of HepG2 cells. This study provides a foundation for understanding the mechanism of selective induction of apoptosis in cancer cells by NG nanoparticles and designing more effective chemotherapeutical agents.Carbon-based materials have been widely used in the biomedical fields including drug delivery and cancer therapies. In this paper, a recently synthesized three-dimensional nanographene (NG) based on triptycene self-assembles into nanoparticles which selectively kill human hepatocellular carcinoma HepG2 cells as compared to human normal liver HL7702 cells. Obvious differences in cellular accumulation, the endocytic pathway and intracellular trafficking of NG nanoparticles are observed in HepG2 cells and HL7702 cells. Further studies reveal that NG nanoparticles significantly increase the levels of reactive oxygen species (ROS) in HepG2 cells, but not in HL7702

  3. Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders of induction chemotherapy-based larynx preservation protocols.

    PubMed

    Vourexakis, Zacharias; Le Ridant, Anne-Marie; Dulguerov, Pavel; Janot, François

    2015-07-01

    Induction chemotherapy-based larynx preservation protocols use chemotherapy to select exclusively patients with 'chemosensitive' tumors for a nonsurgical treatment with radiation therapy. This study on pyriform sinus squamous cell carcinoma (SCC) is interested in the oncological outcome of treatment based on radiation therapy when offered to patients with tumors responding to induction chemotherapy. This was a retrospective cohort study. The cohort included good responders to induction chemotherapy, subsequently treated with definite radiation therapy (with or without concomitant chemotherapy) for pyriform sinus SCC, in a tertiary referral cancer center. The primary endpoints were overall, laryngectomy-free and disease-free survival and the secondary endpoints were analysis of treatment failures and possibilities of salvage treatment. Forty-two patients fulfilled the inclusion criteria and were retained for analysis; 7% were stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5 years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ≈ 0.08), respectively. For the same intervals, the laryngectomy-free survival was 90% (38/42), 69% (29/42) and 50% (SE ≈ 0.08), respectively. The estimated 5-year disease-free survival was also 50%. Disease-free survival was significantly better for N0 patients. There was a 28% recurrence rate, mainly in the primary tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly, more than one-third of all oncologic failures occurred beyond the first 3 years of follow-up. Salvage treatment was not possible or definitely inefficient in at least 2/3 of all recurrences. In candidates for larynx preservation for a pyriform sinus SCC, good response to induction chemotherapy followed by definite radiation therapy seems to be associated with a more favorable prognosis. Nevertheless, in case of locoregional recurrence the possibilities for efficient salvage treatment are limited.

  4. Gene expression analysis of biopsy samples reveals critical limitations of transcriptome-based molecular classifications of hepatocellular carcinoma.

    PubMed

    Makowska, Zuzanna; Boldanova, Tujana; Adametz, David; Quagliata, Luca; Vogt, Julia E; Dill, Michael T; Matter, Mathias S; Roth, Volker; Terracciano, Luigi; Heim, Markus H

    2016-04-01

    Molecular classification of hepatocellular carcinomas (HCC) could guide patient stratification for personalized therapies targeting subclass-specific cancer 'driver pathways'. Currently, there are several transcriptome-based molecular classifications of HCC with different subclass numbers, ranging from two to six. They were established using resected tumours that introduce a selection bias towards patients without liver cirrhosis and with early stage HCCs. We generated and analyzed gene expression data from paired HCC and non-cancerous liver tissue biopsies from 60 patients as well as five normal liver samples. Unbiased consensus clustering of HCC biopsy profiles identified 3 robust classes. Class membership correlated with survival, tumour size and with Edmondson and Barcelona Clinical Liver Cancer (BCLC) stage. When focusing only on the gene expression of the HCC biopsies, we could validate previously reported classifications of HCC based on expression patterns of signature genes. However, the subclass-specific gene expression patterns were no longer preserved when the fold-change relative to the normal tissue was used. The majority of genes believed to be subclass-specific turned out to be cancer-related genes differentially regulated in all HCC patients, with quantitative rather than qualitative differences between the molecular subclasses. With the exception of a subset of samples with a definitive β-catenin gene signature, biological pathway analysis could not identify class-specific pathways reflecting the activation of distinct oncogenic programs. In conclusion, we have found that gene expression profiling of HCC biopsies has limited potential to direct therapies that target specific driver pathways, but can identify subgroups of patients with different prognosis. PMID:27499918

  5. A Comparison of Three Transarterial Lipiodol-Based Formulations for Hepatocellular Carcinoma: In Vivo Biodistribution Study in Humans

    SciTech Connect

    Yu, Simon Chun Ho Leung, Thomas Wai Tong; Lau, Wan Yee; Lee, Nelson; Hui, Edwin Pun; Yeo, Winnie; Lai, Paul Bo San; Mok, Tony Shu Kam

    2008-03-15

    This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 (p = 0.014) and day 28 (p = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations.

  6. Pharmacophore-based screening targeted at upregulated FN1, MMP-9, APP reveals therapeutic compounds for nasopharyngeal carcinoma.

    PubMed

    Lai, Catherine Jessica; Tay, Boon Hunt

    2016-02-01

    Nasopharyngeal carcinoma (NpC) is rare in the west but common in Southeast Asia and only a few other locations. With the limited geographic incidence, it is relatively under-studied. It also has as co-determinant the Epstein-Barr virus (EBV), which may adapt to NpC therapies, so not only must a therapeutic compound be found, the discovery process must be rapid, to cope with the changing basis of the EBV. An R-based computer workbench, Mendel, was developed so biologists could quickly upload genomic data, pre-process them, and identify upregulated and downregulated genes. Mendel was used on 10 control and 31 diseased cell lines to discover 3 differentially expressed genes (DEGs) that meet thresholds on fold-changes, 3-clique membership, pathway constraints, and druggability. From the DEGs, we conducted a pharmacophore-based screening of 22,723,923 compounds using protein-protein interaction anchor-residue clusters as binding sites. Of the 4 hits, 3 passed all the ADME-Tox tests. These 3 hit compounds, 6-(4-iminiocyclohexa-2,5-dien-1-ylidene)-4-(thiazol-2-ylcarbamoyl)-1H-pyrimidine-2-thiolate, 1-[4-[2-[(3R)-3-hydroxy-2-oxo-indolin-3-yl]acetyl]phenyl]-3-phenyl-urea, and (2R)-N4-[4-(1-piperidyl)cyclohexyl]morpholine-2,4-dicarboxamide have predicted pIC50 values superior to the current drugs fluorouracil (5-FU) and taxotere, which have side effects and face EBV drug resistance. PMID:26773938

  7. Thyroid carcinoma after radioiodide therapy for hyperthyroidism. Analysis based on age, latency, and administered dose of I-/sup 131/

    SciTech Connect

    Spencer, R.P.; Chapman, C.N.; Rao, H.

    1983-05-01

    Twenty-five reports in the medical literature of thyroid carcinomas which were detected after radioiodide therapy for hyperthyroidism were reviewed. These cases did not show a usual characteristic of radiation-associated tumors, namely a long latency period. That is, in 8/25 the latency period was under five years, and the mean latency was only 7.3 years. Further, there was no relationship between latency and age at treatment, or between latency and the dose of radioiodide employed. In 15/25 of the cases, there were known thyroid nodules. Three of the patients had thyroiditis (which itself has a correlation with thyroid carcinoma), and one individual had prior head and neck external radiation. There was no substantiating evidence that radioiodide treatment for hyperthyroidism was the cause of these thyroid carcinomas.

  8. Basal Cell Carcinoma (BCC)

    MedlinePlus

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  9. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. MTC is very rare. It can occur in children and adults. Unlike other types ...

  10. [Incretin-based antidiabetic treatment and diseases of the pancreas (pancreatitis, pancreas carcinoma)].

    PubMed

    Jermendy, György

    2016-04-01

    In the last couple of years incretin-based antidiabetic drugs became increasingly popular and widely used for treating patients with type 2 diabetes. Immediately after launching, case reports and small case series were published on the potential side effects of the new drugs, with special attention to pancreatic disorders such as acute pancreatitis or pancreatic cancer. As clinical observations accumulated, these side-effects were noted with nearly all drugs of this class. Although these side-effects proved to be rare, an intensive debate evolved in the literature. Opinion of diabetes specialists and representatives of pharmaceutical industry as well as position statements of different international scientific boards and health authorities were published. In addition, results of randomized clinical trials with incretin-based therapy and meta-analyses became available. Importantly, in everyday clinical practice, the label of the given drug should be followed. With regards to incretins, physicians should be cautious if pancreatitis in the patients' past medical history is documented. Early differential diagnosis of any abdominal pain during treatment of incretin-based therapy should be made and the drug should be discontinued if pancreatitis is verified. Continuous post-marketing surveillance and side-effect analysis are still justified with incretin-based antidiabetic treatment in patients with type 2 diabetes.

  11. Hepatocellular carcinoma.

    PubMed

    Okuda, K

    2000-01-01

    Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite

  12. Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath.

    PubMed

    Kahn, Nicole; Lavie, Ofer; Paz, Moran; Segev, Yakir; Haick, Hossam

    2015-10-14

    Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases. PMID:26352191

  13. Sensorineural Hearing Loss after Combined Intensity Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma12

    PubMed Central

    Wang, Jin; Chen, Yuan-Yuan; Tai, An; Chen, Xue-Lin; Huang, Shao-Ming; Yang, Cungen; Bao, Yong; Li, Ning-Wei; Deng, Xiao-Wu; Zhao, Chong; Chen, Ming; Li, X. Allen

    2015-01-01

    PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60 months, ranging from 28 to 84 months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2 kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4 kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age > 40, with T-stage 4, or who received cumulative cisplatin dose (CCD) > 200 mg/m2 (P = .034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P = .002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1 ml highest dose volume (D0.1 ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1 ml of cochlea (P = .035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1 ml of cochlea, and SOM. PMID:26692526

  14. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-05-01

    Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y. PMID:27467913

  15. Examination of fabrication conditions of acrylate-based hydrogel formulations for doxorubicin release and efficacy test for hepatocellular carcinoma cell.

    PubMed

    Bayramoglu, Gulay; Gozen, Damla; Ersoy, Gozde; Ozalp, V Cengiz; Akcali, K Can; Arica, M Yakup

    2014-01-01

    The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells. PMID:24580096

  16. Single Photon Emission Computed Tomography-Based Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

    SciTech Connect

    Shirai, Shintaro; Sato, Morio Suwa, Kazuhiro; Kishi, Kazushi; Shimono, Chigusa; Kawai, Nobuyuki; Tanihata, Hirohiko; Minamiguchi, Hiroki; Nakai, Motoki

    2009-03-01

    Purpose: To evaluate the safety and efficacy of three-dimensional conformal radiotherapy (3D-CRT) using single photon emission computed tomography (SPECT) in unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods and Materials: Patients with HCC with PVTT in the first branch and/or main trunk were selected for this study. The optimal beam directions for 3D-CRT were explored using a Tc-99m-galactosyl human serum albumin SPECT image for guidance. The SPECT image was classified as either wedge type or localized type. The clinical target volume to a total dose of 45 or 50 Gy per 18-20 fractions included the main tumor and PVTT in the wedge type and PVTT alone in the localized type. Results: Twenty-six patients were enrolled: 18 with wedge type and 8 with localized type. Mean tumor size was 7.1 cm (range, 4.4-12.3 cm). Clinical target volumes of wedge type vs. localized type were 111.2 cm{sup 3} vs. 48.4 cm{sup 3} (p = 0.010), respectively. Mean dose to normal liver and mean dose to functional liver were 1185 cGy and 988 cGy (p = 0.001) in wedge type and 1046 cGy and 1043 cGy (p = 0.658) in localized type, respectively. Despite an incidence of Child-Pugh B and C of 57.7%, no patients experienced radiation-induced liver disease. The progression of PVTT was inhibited, with an incidence of 92.2%; survival rates at 1 and 2 years were 44% and 30%, respectively. Conclusion: Single photon emission computed tomography-based 3D-CRT enables irradiation of both the main tumor and PVTT with low toxicity and promising survival.

  17. Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002–2009: a population-based cohort study

    PubMed Central

    Thein, H.H.; Qiao, Y.; Young, S.K.; Zarin, W.; Yoshida, E.M.; de Oliveira, C.; Earle, C.C.

    2016-01-01

    Background The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. Methods This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. Results We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient–days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008–2009 and 2002–2003 respectively). Conclusions In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control. PMID:27330357

  18. The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma

    PubMed Central

    Zhou, Guan-Qun; Guo, Rui; Zhang, Fan; Zhang, Yuan; Xu, Lin; Zhang, Lu-Lu; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2016-01-01

    Background To evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) using individualized clinical target volumes (CTVs) based on the loco-regional extension patterns of nasopharyngeal carcinoma (NPC). Methods From December 2009 to February 2012, 220 patients with histologically-proven, non-disseminated NPC were prospectively treated with IMRT according to an individualized delineation protocol. CTV1 encompassed the gross tumor volume, entire nasopharyngeal mucosa and structures within the pharyngobasilar fascia with a margin. CTV2 encompassed bilateral high risk anatomic sites and downstream anatomic sites adjacent to primary tumor, bilateral retropharyngeal regions, levels II, III and Va, and prophylactic irradiation was gave to one or two levels beyond clinical lymph nodes involvement. Clinical outcomes and toxicities were evaluated. Results Median follow-up was 50.8 (range, 1.3–68.0) months, four-year local relapse-free, regional relapse-free, distant metastasis-free, disease-free and overall survival rates were 94.7%, 97.0%, 91.7%, 87.2% and 91.9%, respectively. Acute severe (≥ grade 3) mucositis, dermatitis and xerostomia were observed in 27.6%, 3.6% and zero patients, respectively. At 1 year, xerostomia was mild, with frequencies of Grade 0, 1, 2 and 3 xerostomia of 27.9%, 63.3%, 8.3% and 0.5%, respectively. Conclusions IMRT using individualized CTVs provided high rates of local and regional control and a favorable toxicity profile in NPC. Individualized CTV delineation strategy is a promising one that may effectively avoid unnecessary or missed irradiation, and deserve optimization to define more precise individualized CTVs. PMID:26980744

  19. Adrenocortical Carcinoma

    PubMed Central

    Kim, Alex C.; Sabolch, Aaron; Raymond, Victoria M.; Kandathil, Asha; Caoili, Elaine M.; Jolly, Shruti; Miller, Barbra S.; Giordano, Thomas J.

    2014-01-01

    Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC. PMID:24423978

  20. Neuroendocrine carcinoma of the tongue.

    PubMed

    Esmati, Ebrahim; Babaei, Mohammad; Matini, Amirhassan; Ashtiani, Monir Sadat Mirai; Hamed, Ehsan Akbari; Nosrati, Hassan; Razi, Farideh; Ganjalikhani, Maryam

    2015-01-01

    Neuroendocrine carcinoma usually originates from lung. Few data exist in the literature regarding neuroendocrine carcinoma of the tongue. Patient data including history, surgical procedure, histology, and radiology investigations were collected and summarized. A 40-year-old woman was referred after partial glossectomy. Squamous mucosa with neoplasm and cells with round nuclei and light cytoplasm was reported in the tongue biopsy. Immunohistochemistry (IHC) staining was positive for cytokeratin, neuron specific enolase, synaptophysin and chromogranin and negative for leukocyte common antigen. This case showed a high proliferative activity (Ki-67 labeling index were 60%). These IHC findings were in favor of poorly differentiated neuroendocrine carcinoma. After surgery, she received chemotherapy and chemoradiation. The diagnosis of neuroendocrine tumors in the present case is based on immunohistochemical markers and cellular shapes. Postoperative chemoradiotherapy is a critical element of therapy for head and neck high-grade neuroendocrine carcinomas, our patient received this treatment after surgery. PMID:26458666

  1. Development and evaluation of an anchorage-independent agar-based clonal assay for human primary breast carcinoma cells

    SciTech Connect

    Besch, G.J.

    1985-01-01

    The development and evaluation of an anchorage-independent clonal cytotoxic assay for primary human breast carcinoma cells is described in this thesis. This assay was developed in three stages which include: (1) the optimization of the production of a monodispersed cell suspension from solid breast carcinomas, (2) the systematic development of a growth medium for the clonal growth of these cells, and (3) the adaptation of these methods for use in the quantitation of cytotoxicity. The results of these studies indicated that hydrocortisone, fetal bovine serum and red blood cells stimulated the clonal growth of breast carcinoma cells. The optimal concentrations of these three factors were simultaneously determined using response surface methodology. These culture conditions were then used to develop radiation-cytotoxicity assays for both primary and recurrent breast carcinomas. The methodology developed and evaluated in this thesis may be useful to: (1) study the biology and radiobiology of human breast cancer, (2) customize the treatment of individual breast cancer patients, and (3) identify and/or develop new drugs and/or other treatment modalities for breast cancer.

  2. [Effect of plant biocomposites based on Georgian tea "per se" and in combination with cisplatin on Walker carcinosarcoma W-256 and Guerin's carcinoma growth rate in rats].

    PubMed

    Zalietok, S P; Orlovs'kyĭ, O A; Hohol', S V; Samoĭlenko, O A; Hulua, L; Kvesitadze, H I

    2006-12-01

    Green tea biocomposite had effectivey hampered the growth of rat Walker W-256 carcinoma and in less extent rat Guerin's carcinoma. Black tea biocomposite had not practically influenced on Guerin's carcinoma growth. The biocomposite from green tea and extract from red vine rind and lemon suppressed at the level of tendency the growth of rat Walker W-256 carcinoma. The biocomposite from green tea and extract from red vine rind had hampered only Guerin's carcinoma growth and at the tendency had increased the growth of W-256 carcinosarcoma growth. This biocomposite increased also considerably the therapeutic efficiency of cisplatin on Guerin's carcinoma. Studed vegetable biocomposites posesses antiinflammatory and antioxidant properties.

  3. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  4. Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling.

    PubMed

    Lee, Hye-Kyung; Ji, Suk; Park, Su-Jin; Choung, Han-Wool; Choi, Youngnim; Lee, Hyo-Jung; Park, Shin-Young; Park, Joo-Cheol

    2015-06-01

    Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Although odontogenic ameloblast-associated protein (ODAM) is expressed in the JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in the normal JE of healthy teeth but absent in the pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from the JE following onset with JE attachment loss and detected in gingival crevicular fluid. ODAM induced RhoA activity and the expression of downstream factors, including ROCK (Rho-associated kinase), by interacting with Rho guanine nucleotide exchange factor 5 (ARHGEF5). ODAM-mediated RhoA signaling resulted in actin filament rearrangement. Reduced ODAM and RhoA expression in integrin β3- and β6-knockout mice revealed that cytoskeleton reorganization in the JE occurred via integrin-ODAM-ARHGEF5-RhoA signaling. Fibronectin and laminin activated RhoA signaling via the integrin-ODAM pathway. Finally, ODAM was re-expressed with RhoA in regenerating JE after gingivectomy in vivo. These results suggest that ODAM expression in the JE reflects a healthy periodontium and that JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. We also propose that ODAM could be used as a biomarker of periodontitis and peri-implantitis.

  5. Time-dose relationships for local tumor control and complications following irradiation of squamous cell carcinoma of the base of tongue

    SciTech Connect

    Gardner, K.E.; Parsons, J.T.; Mendenhall, W.M.; Million, R.R.; Cassisi, N.J.

    1987-04-01

    Between October 1964 and September 1981, 114 previously untreated patients with squamous cell carcinoma of the base of the tongue were treated with curative intent by a radical course of irradiation at the University of Florida. With a minimum 2-year follow-up, local control was achieved in 78, 65, 76, and 17% of T1, T2, T3, and T4 lesions, respectively. Control results could be correlated with time-dose factors and treatment techniques. No patient required mandibulectomy for osteoradionecrosis following radiation therapy. Complications of bone and soft tissue could not be related to time-dose factors.

  6. Adrenocortical carcinoma.

    PubMed

    Baudin, Eric

    2015-06-01

    Recent developments in the treatment of adrenocortical carcinoma (ACC) include diagnostic and prognostic risk stratification algorithms, increasing evidence of the impact of historical therapies on overall survival, and emerging targets from integrated epigenomic and genomic analyses. Advances include proper clinical and molecular characterization of all patients with ACC, standardization of proliferative index analyses, referral of these patients to large cancer referral centers at the time of first surgery, and development of new trials in patients with well-characterized ACC. Networking and progress in the molecular characterization of ACC constitute the basis for significant future therapeutic breakthroughs. PMID:26038209

  7. Thyroid carcinoma

    SciTech Connect

    Friedman, M.; Skolnik, E.M.; Baim, H.M.; Becker, S.P.; Katz, A.H.; Mantravadi, R.V.

    1980-12-01

    Differentiated thyroid carcinoma was studied with regard to mode of presentation, initial findings, treatment and survival. The classic signs, symptoms, physical and scan findings were found to be present in approximately 70% of the patients. Prognosis was found to be dependent on age of presentation more than any other factor. Patients with prior exposure to radiation were found to have more extensive disease and require more extensive surgery but ultimately had the same prognosis for 15-year cure. Treatment for distant metastatic disease by surgery, radioactive iodine and external radiation all resulted in long-term survival in certain cases.

  8. Epirubicin-based compared with docetaxel-based chemotherapy for advanced gastric carcinoma: A systematic review and meta-analysis.

    PubMed

    Petrioli, Roberto; Roviello, Giandomenico; Zanotti, Laura; Roviello, Franco; Polom, Karol; Bottini, Alberto; Marano, Luigi; Francini, Edoardo; Marrelli, Daniele; Generali, Daniele

    2016-06-01

    Docetaxel or Epirubicin-based regimens are both approved for the treatment of metastatic gastric cancer. We perform a systemic review with metanalysis to evaluate the efficacy and toxicities of docetaxel-based chemotherapy compared with epirubicin-containing regimens. A metaanalysis of randomized studies in accordance with the preference guidelines for reported items in systematic reviews and meta-analyses is performed in which the databases of PubMed, the Cochrane Library, and the ASCO University Meeting were searched for relevant publications. The primary outcome was efficacy, the secondary toxicities. A total of 553 cases were included in the meta-analysis; 278 received epirubicin-based treatment and 313 received docetaxel. The pooled risk ratio to achieve an objective response and a disease control rate were 1.08 (95% CI 0.85-1.37; P=0.52) and 0.90 (95% CI 0.75-1.08; P=0.27) respectively. EPI arm showed a decrease in the risk of neutropenia, anemia, fatigue, asthenia and diarrhea, paraesthesia; docetaxel arm showed a decrease in the risk of leucopenia, thrombocytopenia, anorexia, nausea, nausea-vomiting, stomatitis and neutropenic fever. The results of our study suggest a similar activity of docetaxel and epirubicin-based chemotherapeutic regimens in metastatic gastric cancer. Other parameters as, comorbidity, concomitant diseases and prior therapies should be taken into account to address the clinician's choice in selecting the best therapeutical approach for any single patient. PMID:27083592

  9. Everolimus in the management of metastatic renal cell carcinoma: an evidence-based review of its place in therapy

    PubMed Central

    Buti, Sebastiano; Leonetti, Alessandro; Dallatomasina, Alice; Bersanelli, Melissa

    2016-01-01

    Introduction Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. Aim The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. Evidence review Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI). The role of this drug in first-line setting has been investigated in Phase II trials, with no significant clinical benefit, even in combination with bevacizumab. Everolimus activity in non-clear cell RCC is supported by two randomized Phase II trials that confirmed the benefit in second-line setting but not in first line. Recently, two randomized Phase III trials (METEOR and CheckMate 025) demonstrated the inferiority of everolimus in second-line setting compared to the TKI cabozantinib and to the immune checkpoint inhibitor nivolumab, respectively. Moreover, a recent Phase II study demonstrated a significant benefit for the second-line combination treatment with everolimus plus lenvatinib (a novel TKI) in terms of progression-free survival and overall survival compared to the single-agent everolimus. Basing on preclinical data, the main downstream effectors of mTOR cascade, S6RP and its phosphorylated form, could be good predictive biomarkers of response to everolimus. The safety profile of the drug is favorable, with a good cost-effectiveness compared to second-line sorafenib or axitinib, and no significant impact on the quality of life of treated

  10. Everolimus in the management of metastatic renal cell carcinoma: an evidence-based review of its place in therapy

    PubMed Central

    Buti, Sebastiano; Leonetti, Alessandro; Dallatomasina, Alice; Bersanelli, Melissa

    2016-01-01

    Introduction Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. Aim The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. Evidence review Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI). The role of this drug in first-line setting has been investigated in Phase II trials, with no significant clinical benefit, even in combination with bevacizumab. Everolimus activity in non-clear cell RCC is supported by two randomized Phase II trials that confirmed the benefit in second-line setting but not in first line. Recently, two randomized Phase III trials (METEOR and CheckMate 025) demonstrated the inferiority of everolimus in second-line setting compared to the TKI cabozantinib and to the immune checkpoint inhibitor nivolumab, respectively. Moreover, a recent Phase II study demonstrated a significant benefit for the second-line combination treatment with everolimus plus lenvatinib (a novel TKI) in terms of progression-free survival and overall survival compared to the single-agent everolimus. Basing on preclinical data, the main downstream effectors of mTOR cascade, S6RP and its phosphorylated form, could be good predictive biomarkers of response to everolimus. The safety profile of the drug is favorable, with a good cost-effectiveness compared to second-line sorafenib or axitinib, and no significant impact on the quality of life of treated

  11. Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case-control study conducted in the greater Boston area.

    PubMed

    Langevin, Scott M; McClean, Michael D; Michaud, Dominique S; Eliot, Melissa; Nelson, Heather H; Kelsey, Karl T

    2013-12-01

    Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case-control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation.

  12. Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case–control study conducted in the greater Boston area

    PubMed Central

    Langevin, Scott M; McClean, Michael D; Michaud, Dominique S; Eliot, Melissa; Nelson, Heather H; Kelsey, Karl T

    2013-01-01

    Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case–control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation. PMID:24403272

  13. Hepatocellular carcinoma.

    PubMed

    Buendia, Marie-Annick; Neuveut, Christine

    2015-02-01

    The hepatitis B virus (HBV) is a widespread human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma (HCC). Recent sequencing technologies have refined our knowledge of the genomic landscape and pathogenesis of HCC, but the mechanisms by which HBV exerts its oncogenic role remain controversial. In a prevailing view, inflammation, liver damage, and regeneration may foster the accumulation of genetic and epigenetic defects leading to cancer onset. However, a more direct and specific contribution of the virus is supported by clinical and biological observations. Among genetically heterogeneous HCCs, HBV-related tumors display high genomic instability, which may be attributed to the ability of HBV to integrate its DNA into the host cell genome, provoking chromosomal alterations and insertional mutagenesis of cancer genes. The viral transactivator HBx may also participate in transformation by deregulating diverse cellular machineries. A better understanding of the complex mechanisms linking HBV to HCC will improve prevention and treatment strategies. PMID:25646384

  14. Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Schell, Amy; Ley, Jessica; Wu, Ningying; Trinkaus, Kathryn; Wildes, Tanya Marya; Michel, Loren; Thorstad, Wade; Gay, Hiram; Lewis, James; Rich, Jason; Diaz, Jason; Paniello, Randal C; Nussenbaum, Brian; Adkins, Douglas R

    2015-01-01

    We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC. PMID:25619559

  15. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma.

    PubMed

    Incorvaia, Lorena; Bronte, Giuseppe; Bazan, Viviana; Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-04-19

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

  16. 68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies

    PubMed Central

    Drion, Pierre; Meffre, Geneviève; Bernard, Claire; Duwez, Luc; Lepareur, Nicolas; Couturier, Olivier; Hindré, François

    2016-01-01

    Purpose This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma. Methods Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging. Results Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part. Conclusion SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma. PMID:27741267

  17. Interlaboratory comparison in HercepTest assessment of HER2 protein status in invasive breast carcinoma fixed with various formalin-based fixatives.

    PubMed

    Hashizume, Kaoru; Hatanaka, Yutaka; Kamihara, Yuki; Kato, Tomoyuki; Hata, Sakae; Akashi, Shizuka; Kato, Toshihiko; Koyatsu, Junichi; Tani, Yoichi; Tsujimoto, Masahiko; Tsuda, Hitoshi

    2003-12-01

    Although formalin-based fixatives are used in pathologic laboratories, there is no strictly standardized fixation protocol in Japan. To examine interlaboratory variation caused by different conditions of fixation in the assessment of human epidermal growth factor receptor (HER) 2 status on pathologic tissues, 274 archival invasive breast carcinomas from 5 different laboratories were evaluated using the HercepTest. In 1 laboratory in which 10% neutral buffered formalin was used, as recommended by the manufacturer, the overexpression rate was 22.4% and fell within the statistical expected range (20%-30%) for HER2 overexpression in breast carcinomas. The overexpression rates in the other 4 laboratories, in which either 20% nonbuffered formalin or 15% neutral buffered formalin was used, were near the expected range for HER2 overexpression. To clarify the influence of prolonged formalin fixation on the HercepTest, we compared 1-day with 7-day fixations using 36 cases fixed with 20% nonbuffered formalin. Of the 36 cases, 7 showed 3+ staining with 1-day fixation and sustained the same scoring results with 7-day fixation, although the staining intensities in these cases were reduced with the prolonged fixation. These results indicated that the immunohistochemical assessment of HER2 status with the HercepTest was comparatively resistant to prolonged fixation conditions and provided stable staining results in positive cases, particularly 3+ patients.

  18. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

    PubMed Central

    Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-01-01

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition. Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC. PMID:26872372

  19. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    PubMed

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

  20. Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study.

    PubMed

    Zheng, Yi-Zi; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥ 50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289-1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients. PMID:27053333

  1. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  2. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  3. Squamous Cell Carcinoma (SCC)

    MedlinePlus

    ... A A Squamous cell carcinoma typically develops in sun-damaged skin in fair-skinned patients. Overview Squamous ... skin cancer. Squamous cell carcinoma usually occurs on sun-damaged skin, especially in light-skinned individuals with ...

  4. [Hepatocellular carcinoma].

    PubMed

    Colombo, Massimo; Sangiovanni, Angelo

    2016-07-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and the first in patients with compensated cirrhosis. Chronic infection with hepatitis B and C, alcohol, smoking, exposure to aflatoxin and metabolic syndrome, associated with diabetes and obesity are the main etiological factors. Regardless of etiology, patients with cirrhosis stand as the category at higher risk of developing HCC, and indeed are the target of surveillance programs aimed to the early diagnosis of HCC, the only chance to reduce HCC-related mortality. This notwithstanding, International Scientific Societies have issued recommendations for the management of HCC, a significant number of patients are treated outside guidelines, due to several reasons. Among queries still unsolved, the impact of biological characterization of HCC, along with the biological profiling of patients at risk of developing HCC represent main challenges for the future. Treatment personalization and multimodal treatment being further challenges. This chapter summarizes the recommendations for surveillance, diagnosis and treatment of HCC and focus on future directions. PMID:27571469

  5. Engineering α-fetoprotein-based gene vaccines to prevent and treat hepatocellular carcinoma: review and future prospects.

    PubMed

    He, Yukai; Hong, Yuan; Mizejewski, Gerald J

    2014-01-01

    Activation of a patient's immune system offers an attractive approach to prevent and treat hepatocellular carcinoma (HCC). However, the antitumor efficacy of current HCC vaccines was weak owing to insufficient immune activation of targeting self/tumor antigens. We recently found that epitope-optimized α-fetoprotein effectively activated CD8 T cells and generated potent antitumor effects in the carcinogen-induced autochthonous HCC mouse model. We predict that the same antigen engineering approach of epitope-optimization will enable us to develop effective human vaccines to prevent HCC recurrence after liver resection. The engineered human HCC vaccines may also allow us to identify high-affinity T-cell receptors and antibodies that can be used to reprogram T cells to treat HCC tumors via adoptive transfer.

  6. Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication in the human oral squamous carcinoma cell line SAS.

    PubMed

    Chai, Hongbo; Hazawa, Masaharu; Hosokawa, Yoichiro; Igarashi, Jun; Suga, Hiroaki; Kashiwakura, Ikuo

    2012-01-01

    The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs was investigated on the human oral squamous carcinoma cell line SAS. One analog induced G2/M phase arrest at 5.3-10.6 µM and induced polyploidy at a higher dose (21.2 µM). Importantly, treatment of SAS cells with a combination of the AHL analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit clonogenic survival of SAS cells; however, its radiosensitizing effects were relative to not X-irradiation-induced apoptosis but mitotic failure following enhanced expression of Aurora A and B. These results suggest that the active AHL analog showed growth-suppressive and radiosensitizing effects, which involve polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell line.

  7. A population-based case-control study of occupation and renal cell carcinoma risk in Iowa.

    PubMed

    Zhang, Yawei; Cantor, Kenneth P; Lynch, Charles F; Zheng, Tongzhang

    2004-03-01

    A case-control study involving 406 incident cases and 2,434 controls was conducted in Iowa to examine the association between occupational exposures and renal cell carcinoma risk. After adjusting for major confounders, an increased risk was observed for men among mechanics and repairers (odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.2-2.9); assemblers (OR 2.5, 95% CI = 0.8-7.6); automotive dealership and service station employees (OR 1.9, 95% CI = 0.9-3.9); wholesale traders of durable goods (OR 1.5, 95% CI = 0.7-3.2); farm product vendors (OR 4.4, 95% CI = 1.3-15.5); service organization managers (OR 2.2, 95% CI = 1.0-5.1); financial specialists (OR 2.7, 95% CI = 1.0-7.6); sales occupation supervisors (OR 1.8, 95% CI = 1.0-3.3); guards (OR 5.4, 95% CI = 1.4-20.7); and general farm workers (OR 1.9, 95% CI = 1.0-3.7). Among women, an increased risk was found for employees in depository institutions (OR 3.6, 95% CI = 1.1-11.3); colleges and universities (OR 7.6-95% CI = 2.3-25.6); and retail, including those in grocery stores (OR 2.2, 95% CI = 1.0-4.7). Our results indicate that occupational exposures may increase the risk of renal cell carcinoma. PMID:15091286

  8. A population-based case-control study of occupation and renal cell carcinoma risk in Iowa.

    PubMed

    Zhang, Yawei; Cantor, Kenneth P; Lynch, Charles F; Zheng, Tongzhang

    2004-03-01

    A case-control study involving 406 incident cases and 2,434 controls was conducted in Iowa to examine the association between occupational exposures and renal cell carcinoma risk. After adjusting for major confounders, an increased risk was observed for men among mechanics and repairers (odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.2-2.9); assemblers (OR 2.5, 95% CI = 0.8-7.6); automotive dealership and service station employees (OR 1.9, 95% CI = 0.9-3.9); wholesale traders of durable goods (OR 1.5, 95% CI = 0.7-3.2); farm product vendors (OR 4.4, 95% CI = 1.3-15.5); service organization managers (OR 2.2, 95% CI = 1.0-5.1); financial specialists (OR 2.7, 95% CI = 1.0-7.6); sales occupation supervisors (OR 1.8, 95% CI = 1.0-3.3); guards (OR 5.4, 95% CI = 1.4-20.7); and general farm workers (OR 1.9, 95% CI = 1.0-3.7). Among women, an increased risk was found for employees in depository institutions (OR 3.6, 95% CI = 1.1-11.3); colleges and universities (OR 7.6-95% CI = 2.3-25.6); and retail, including those in grocery stores (OR 2.2, 95% CI = 1.0-4.7). Our results indicate that occupational exposures may increase the risk of renal cell carcinoma.

  9. Hepatocellular carcinoma.

    PubMed

    Llovet, Josep M; Zucman-Rossi, Jessica; Pikarsky, Eli; Sangro, Bruno; Schwartz, Myron; Sherman, Morris; Gores, Gregory

    2016-01-01

    Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches. PMID:27158749

  10. A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-06-30

    Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC) Patients Who Are Resistant or Ineligible/Intolerant to Platinum-based Chemotherapy.; Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma

  11. PAX 2: a novel Müllerian marker for serous papillary carcinomas to differentiate from micropapillary breast carcinoma.

    PubMed

    Chivukula, Mamatha; Dabbs, David J; O'Connor, Siobhan; Bhargava, Rohit

    2009-11-01

    Ovarian serous papillary carcinoma, although rarely metastasizing to the breast, is often challenging based on morphology alone, particularly from the micropapillary variant of breast carcinoma. Gross cystic disease fluid protein-15, although a specific marker, can be negative in up to 50% of breast carcinomas. Wilm's tumor gene 1 (WT-1) has been identified as a useful marker to differentiate metastatic ovarian serous papillary carcinoma from primary breast carcinoma; however, it has recently been shown in the micropapillary variant of the primary breast carcinoma making it a less specific marker. PAX 2, a nuclear transcription factor, was recently observed in ovarian serous papillary carcinomas. In this study of 89 breast carcinoma cases, 26 micropapillary carcinoma, and 63 nonmicropapillary carcinoma types were retrieved from our pathology archives, represented on a single tissue microarray (TMA) with a 3-fold redundancy (TMA-1, TMA-2). In addition, whole tissue sections of a variety of benign and neoplastic müllerian tissues were surveyed with the PAX 2 immunostain. All cases were stained with rabbit polyclonal PAX 2 antibody and, in addition, the 5 metastatic ovarian serous carcinoma cases were stained with WT-1 as well for comparison. Only nuclear staining was considered positive. All primary breast carcinomas represented on TMA-1 and TMA-2 were entirely negative for PAX 2 100% (89/89), whereas 100% (5/5) of all metastatic ovarian serous carcinomas showed moderate-to-strong staining. PAX 2 expression was comparable with WT-1 as well in the metastatic ovarian serous carcinoma group. We therefore conclude that PAX 2 is a promising new, sensitive, and specific müllerian immunomarker for ovarian serous carcinomas (primary and metastatic).

  12. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  13. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-02-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m{sup 2}]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade >=3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  14. Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.

    PubMed

    Liu, Xi-Yu; Jiang, Yi-Zhou; Liu, Yi-Rong; Zuo, Wen-Jia; Shao, Zhi-Ming

    2015-08-01

    Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P < 0.001). Five-year OS rates were 95.3% versus 90.1% (P < 0.001). After adjustment for common clinicopathological factors in the multivariate analysis, patients with ICC showed limited DSS advantage over the IDC group (HR = 0.75, 95% CI: 0.38-1.51, P = 0.421). No significant difference in DSS nor OS was observed in matched groups between ICC and IDC. Analysis among ER-positive patients revealed similar prognostic factors as among all patients. Survival analysis in different tumor grade subgroups showed no significant difference between ICC and IDC.ICCs have unique clinicopathological characteristics, higher rates of breast-conserving surgery, and more favorable prognosis compared to the overall IDC population. Difference in tumor grade between the 2 groups may partially explain the different outcome. Improved clinical and biological understanding of ICC

  15. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

  16. Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis

    SciTech Connect

    Rakovitch, Eileen; Narod, Steven A.; Nofech-Moses, Sharon; Hanna, Wedad; Thiruchelvam, Deva; Saskin, Refik; Taylor, Carole; Tuck, Alan; Youngson, Bruce; Miller, Naomi; Done, Susan J.; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A.; Bonin, Michel; Metcalfe, Stephanie; Paszat, Lawrence

    2013-07-01

    Purpose: To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. Methods and Materials: All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. Results: We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). Conclusions: Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.

  17. Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals

    NASA Astrophysics Data System (ADS)

    Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T.

    2012-07-01

    Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.

  18. Expression of genes responsible for the repair of mispaired bases of the DNA (MLH1) in invasive ductal breast carcinoma.

    PubMed

    Milanović, Rudolf; Stanec, Sanda; Stanec, Mladen; Korusić, Andelko; Husedzinović, Ino; Razumović, Jasminka Jakić

    2013-09-01

    Breast cancer is a heterogeneous group of diseases determined and distinguished by cellular type, gene expression and clinical signs and symptoms. Identification of histological and biological markers is of great value in predicting the progression of tumor growth and anticipating the expected response to various treatment options. Due to a high degree of cell proliferation in breast tumors and high genetic instability of these tumors, as a consequence of defective DNA repair mechanisms, chemotherapy as a treatment option often renders very successful results. During our scientific research we wanted to determine the involvement of the genetic polymorphisms of DNA mismatch repair system (MLH1 gene) and the subsequent development of breast carcinoma. This study included 108 patients who were surgically treated for invasive breast cancer at the Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital "Dubrava". The expression of the MLH1 gene was determined by immunohistochemical methods. The results showed that 82.9% of tumor cells expressed the MLH1 gene. Analysis of survival rate for patients with invasive ductal breast cancer showed a statistically significant (p = 0.043) correlation with the expression of MLH1 genes. The overall five year survival rate of our patients was 78.7%. These results indicate that there is a possible involvement of MLH1 gene in the progression and development of breast cancer.

  19. An analysis of the efficacy of serial screening for familial nasopharyngeal carcinoma based on Markov chain models.

    PubMed

    Choi, Cheuk Wai; Lee, Michael C H; Ng, Wai Tong; Law, Lai Yau; Yau, Tsz Kok; Lee, Anne W M

    2011-03-01

    Treatment of nasopharyngeal carcinoma (NPC) can be improved by early detection of the disease as treatment outcome worsens with disease's progression. This can be achieved with a mass screening program using Epstein Barr virus (EBV) serology and nasopharyngoscopy. The efficacy of any screening strategy should be evaluated before putting it into practice. Such evaluation is ideally performed with simulation as time and cost often preclude the evaluation by randomized trial. This study simulated and compared the outcomes of 4 screening strategies over a period of 12 years: (A) Annual screening, (B) biennial screening, (C) triennial screening, and (D) triennial screening for participants tested EBV negative and annual screening once the participants are tested EBV positive. Progression of the disease was divided into 4 phases and calculated by applying Markov chain model. Parameters of the transition matrix and probabilities were estimated using data from previous screening results of 1,072 family members of NPC patients. The early detection rates with strategies A, B, C and D are 88, 79, 71 and 87% respectively. The 5-year overall survival with screening is 10-12% higher than that without and is the highest with strategies A and D. Strategy D, however, requires only 64% screening tests compared with strategy A and has almost identical resultant disease stage distribution to strategy A. We concluded that strategy D offered the highest efficacy for NPC screening of family members of NPC patients among the four strategies studied. PMID:21052850

  20. Gene expression profiling of archival tongue squamous cell carcinomas provides sub-classification based on DNA repair genes.

    PubMed

    Rentoft, Matilda; Laurell, Göran; Coates, Philip John; Sjöström, Björn; Nylander, Karin

    2009-12-01

    A subgroup of patients with squamous cell carcinoma of the head and neck (SCCHN) comprise young persons under the age of 40, who have not been heavily exposed to the classical risk factors, smoking and alcohol. The number of SCCHN in young adults, particularly tongue tumours, is increasing in several parts of the world. Here we employed a novel gene expression array methodology specifically developed for analysis of degraded RNA and investigated the expression of 502 cancer-related genes in archival paraffin-embedded SCCHN of the tongue from young (< or =40) and elderly patients (> or =50). Genes detected as de-regulated in tumours compared to non-malignant controls were in concordance with results from earlier studies of fresh frozen material. No genes were detected as significantly differentially expressed between young and old patients suggesting that the overall pathobiology of SCCHN is similar in young and old. Unsupervised clustering divided tumours into three groups, irrespective of age, where several differentially expressed DNA repair genes were a prominent separation factor. High levels of DNA repair genes associated with impaired therapeutic response to radiation, suggesting that DNA repair genes play a role in clinical outcome after radiotherapy.

  1. Computer Based Correlation of the Texture of P63 Expressed Nuclei with Histological Tumour Grade, in Laryngeal Carcinomas

    PubMed Central

    Ninos, Konstantinos; Kalatzis, Ioannis; Ravazoula, Panagiota; Sakelaropoulos, George; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2014-01-01

    Background. P63 immunostaining has been considered as potential prognostic factor in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible correlation between the texture of P63-stained nuclei and the tumor's grade could be of value to diagnosis, since this may be related to biologic information imprinted as texture on P63 expressed nuclei. Objective. To investigate the association between P63 stained nuclei and histologic grade in laryngeal tumor lesions. Methods. Biopsy specimens from laryngeal tumour lesions of 55 patients diagnosed with laryngeal squamous cell carcinomas were immunohistochemically (IHC) stained for P63 expression. Four images were digitized from each patient's IHC specimens. P63 positively expressed nuclei were identified, the percentage of P63 expressed nuclei was computed, and 118 textural, morphological, shape, and architectural features were calculated from each one of the 55 laryngeal lesions. Data were split into the low grade (21 grade I lesions) and high grade (34 grade II and grade III lesions) classes for statistical analysis. Results. With advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower image intensity, more inhomogeneous, of higher local contrast, contained smaller randomly distributed dissimilar structures and had irregular shape. Conclusion. P63 expressed nuclei contain important information related to histologic grade. PMID:25763351

  2. Gene Expression Patterns in Ovarian Carcinomas

    PubMed Central

    Schaner, Marci E.; Ross, Douglas T.; Ciaravino, Giuseppe; Sørlie, Therese; Troyanskaya, Olga; Diehn, Maximilian; Wang, Yan C.; Duran, George E.; Sikic, Thomas L.; Caldeira, Sandra; Skomedal, Hanne; Tu, I-Ping; Hernandez-Boussard, Tina; Johnson, Steven W.; O'Dwyer, Peter J.; Fero, Michael J.; Kristensen, Gunnar B.; Børresen-Dale, Anne-Lise; Hastie, Trevor; Tibshirani, Robert; van de Rijn, Matt; Teng, Nelson N.; Longacre, Teri A.; Botstein, David; Brown, Patrick O.; Sikic, Branimir I.

    2003-01-01

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers. PMID:12960427

  3. Pancreatic carcinoma: results with fast neutron therapy

    SciTech Connect

    Kaul, R.; Cohen, L.; Hendrickson, F.; Awschalom, M.; Hrejsa, A.F.; Rosenberg, I.

    1981-02-01

    Results of therapy in 31 of 50 patients who were treated for advanced pancreatic carcinoma at Fermi National Accelerator Laboratory are presented here. To date, six patients are alive and four are free of disease. Since the main reason for failure was lack of control of primary tumor, the tumor dose has been increased by 15%. Based on our results, a nationwide study has been launched to assess the effectiveness of neutrons vs photons in the treatment of locally advanced pancreatic carcinoma.

  4. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay

    PubMed Central

    Jia, Kun; Li, Wei; Wang, Feng; Qu, Haixia; Qiao, Yuanyuan; Zhou, Lanping; Sun, Yulin; Ma, Qingwei; Zhao, Xiaohang

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21–1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application. PMID:26993605

  5. Significance of Rumex vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-based on experimental animal studies.

    PubMed

    Shahat, Abdelaaty A; Alsaid, Mansour S; Kotob, Soheir E; Ahmed, Hanaa H

    2015-01-01

    Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant. PMID:26028090

  6. Treatment Outcome and Recursive Partitioning Analysis-Based Prognostic Factors in Patients With Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Kim, Sung- Bae Ahn, Jin Hee; Kim, Yong Hee; Kim, Jong Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho-Young; Shin, Ji Hoon; Cho, Kyung-Ja; Ryu, Jin-Sook; Park, Seung-Il

    2008-07-01

    Purpose: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). Methods and Materials: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. Results: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). Conclusion: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated.

  7. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.

    PubMed

    Bird, Thomas G; Dimitropoulou, Polyxeni; Turner, Rebecca M; Jenks, Sara J; Cusack, Pearce; Hey, Shiying; Blunsum, Andrew; Kelly, Sarah; Sturgeon, Catharine; Hayes, Peter C; Bird, Sheila M

    2016-01-01

    Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance. PMID:27308823

  8. Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

    SciTech Connect

    Konya, Andras; Stephens, L. Clifton; Wright, Kenneth C.

    2011-10-15

    Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization and coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.

  9. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.

    PubMed

    Jia, Kun; Li, Wei; Wang, Feng; Qu, Haixia; Qiao, Yuanyuan; Zhou, Lanping; Sun, Yulin; Ma, Qingwei; Zhao, Xiaohang

    2016-04-26

    Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21-1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application. PMID:26993605

  10. Significance of Rumex vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-based on experimental animal studies.

    PubMed

    Shahat, Abdelaaty A; Alsaid, Mansour S; Kotob, Soheir E; Ahmed, Hanaa H

    2015-01-01

    Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.

  11. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection

    PubMed Central

    Dimitropoulou, Polyxeni; Turner, Rebecca M.; Jenks, Sara J.; Hey, Shiying; Blunsum, Andrew; Kelly, Sarah; Sturgeon, Catharine; Hayes, Peter C.; Bird, Sheila M.

    2016-01-01

    Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009–14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, ‘AFP-detected’ tumours were offered potentially curative management as frequently as ‘US-detected’ HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening ‘HCC-free’ cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10−5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance. PMID:27308823

  12. Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma

    PubMed Central

    Chang, Le; Wang, Guojing; Jia, Tingting; Zhang, Lei; Li, Yulong; Han, Yanxi; Zhang, Kuo; Lin, Guigao; Zhang, Rui; Li, Jinming; Wang, Lunan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy. PMID:26992211

  13. Changes in the planning target volume and liver volume dose based on the selected respiratory phase in respiratory-gated radiation therapy for a hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Baek, Seong-Min

    2013-11-01

    The aim of this study was to quantitatively analyze the changes in the planning target volume (PTV) and liver volume dose based on the respiratory phase to identify the optimal respiratory phase for respiratory-gated radiation therapy for a hepatocellular carcinoma (HCC). Based on the standardized procedure for respiratory-gated radiation therapy, we performed a 4-dimensional computed tomography simulation for 0 ˜ 90%, 30 ˜ 70%, and 40 ˜ 60% respiratory phases to assess the respiratory stability (S R ) and the defined PTV i for each respiratory phase i. A treatment plan was established, and the changes in the PTV i and dose volume of the liver were quantitatively analyzed. Most patients (91.5%) passed the respiratory stability test (S R = 0.111 ± 0.015). With standardized respiration training exercises, we were able to minimize the overall systematic error caused by irregular respiration. Furthermore, a quantitative analysis to identify the optimal respiratory phase revealed that when a short respiratory phase (40 ˜ 60%) was used, the changes in the PTV were concentrated inside the center line; thus, we were able to obtain both a PTV margin accounting for respiration and a uniform radiation dose within the PTV.

  14. Biofunctionalized magnetic nanospheres-based cell sorting strategy for efficient isolation, detection and subtype analyses of heterogeneous circulating hepatocellular carcinoma cells.

    PubMed

    Chen, Lan; Wu, Ling-Ling; Zhang, Zhi-Ling; Hu, Jiao; Tang, Man; Qi, Chu-Bo; Li, Na; Pang, Dai-Wen

    2016-11-15

    Hepatocellular carcinoma (HCC) is an awful threat to human health. Early-stage HCC may be detected by isolation of circulating tumor cells (CTCs) from peripheral blood samples, which is beneficial to the diagnosis and therapy. However, the extreme rarity and high heterogeneity of HCC CTCs have been restricting the relevant research. To achieve an efficient isolation, reliable detection and subtype analyses of heterogeneous HCC CTCs, herein, we present a cell sorting strategy based on anti-CD45 antibody-modified magnetic nanospheres. By this strategy, leukocyte depletion efficiency was up to 99.9% within 30min in mimic clinical samples, and the purity of the spiked HCC cells was improved 265-317-fold. Besides, the isolated HCC cells remained viable at 92.3% and could be directly recultured. Moreover, coupling the convenient, fast and effective cell sorting strategy with specific ICC identification via biomarkers AFP and GPC3, HCC CTCs were detectable in peripheral blood samples, showing the potential for HCC CTC detection in clinic. Notably, this immunomagnetic cell sorting strategy enabled isolating more heterogeneous HCC cells compared with the established EpCAM-based methods, and further achieved characterization of three different CTC subtypes from one clinical HCC blood sample, which may assist clinical HCC analyses such as prognosis or personalized treatment. PMID:27240010

  15. Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma.

    PubMed

    Chang, Le; Wang, Guojing; Jia, Tingting; Zhang, Lei; Li, Yulong; Han, Yanxi; Zhang, Kuo; Lin, Guigao; Zhang, Rui; Li, Jinming; Wang, Lunan

    2016-04-26

    Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy. PMID:26992211

  16. Peptide receptor radionuclide therapy of Merkel cell carcinoma using (177)lutetium-labeled somatostatin analogs in combination with radiosensitizing chemotherapy: a potential novel treatment based on molecular pathology.

    PubMed

    Salavati, Ali; Prasad, Vikas; Schneider, Claus-Peter; Herbst, Rudolf; Baum, Richard Paul

    2012-05-01

    Few studies have been published on the safety and feasibility of synchronous use of peptide receptor radionuclide therapy (PRRNT), as source of internal radiation therapy, in combination with chemotherapy. In this study we reported a 53-year-old man with stage IV Merkel cell carcinoma (MCC), who underwent synchronous internal radiation therapy and chemotherapy. Based on presumable poor prognosis with chemotherapy only, functional similarities of MCC with other neuroendocrine tumors and available evidence of effectiveness and safety of synchronous use of external beam radiation therapy and chemotherapy in treatment of high-risk MCC patients, our interdisciplinary neuroendocrine tumor board recommended him to add PRRNT to his ongoing chemotherapy. He received 2 courses of (177)Lu-DOTATATE(1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-D-Phe1-Tyr3-Thr8-octreotide) in combination with ongoing 8 cycles of liposomal doxorubicin based on standard protocols. Response to therapy was evaluated by (18)F-FDG and (68)gallium-somatostatin-receptor PET/CT. There was an impressive improvement of the clinical symptoms. However, follow-up PET/CT studies showed mixed pattern of response. Synchronous use of PRRNT and radiosensitizing chemotherapy seems safe and feasible in high risk MCC patients, however, further prospective studies and clinical trials are warranted to provide reliable evidence of possible pitfalls and effectiveness of PRRNT and (68)Ga-somatostatin-receptor PET/CT in the management of MCC.

  17. Adrenal metastasis from differentiated thyroid carcinoma documented on post-therapy 131I scan: A case based discussion

    PubMed Central

    Ranade, Rohit; Thapa, Pradeep; Basu, Sandip

    2014-01-01

    Adrenal metastasis is an unusual site of disease involvement in the natural course of differentiated thyroid carcinoma (DTC). This paper discusses the clinical and imaging features of DTC with adrenal metastasis. An unusual case of unilateral solitary asymptomatic adrenal metastasis in the setting of DTC is described in this report with the imaging features including 131I scintigraphy and Fluorodeoxyglucose- Positron emission tomography/computed tomography. The adrenal metastasis was associated with other sites of metastatic disease involvement and was unidentified on initial pre-treatment evaluation studies. All such suspicious lesions should be further evaluated with clinicoradiological correlation by other imaging modalities. A post-radioiodine therapy scan revealed radioiodine uptake in the thyroid bed, sternum and a focus of intense radioiodine concentration in the left suprarenal region. Spot oblique images and single photon emission computed tomography of the upper abdomen was undertaken to ascertain the position and better characterization of the lesion. A subsequent whole body PET-CT (non-contrast) was done which revealed a well defined 6.5 cm × 5.0 cm left adrenal lesion with a SUVmax (standardized uptake value-maximum) of 9.5 in addition to a fluorodeoxyglucose avid osteolytic sternal lesion. The serum thyroglobulin level was significantly raised (more than 250 ng/mL) with thyroid stimulating hormone being 4.9 μΙU/mL (even following an adequate period of levothyroxine withdrawal), indicating the functioning nature of the metastases. In addition to demonstrating an atypical site of metastatic disease in DTC patients, this case emphasizes the importance of carefully interpreting and correlating a post radio-iodine therapy scan, particularly those with focal abdominal radio-iodine uptake which could aid in detecting metastatic lesions that are not characterized or identified on initial evaluation. The other important feature that can be deciphered from

  18. Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma.

    PubMed

    Haylock, Anna-Karin; Spiegelberg, Diana; Mortensen, Anja C; Selvaraju, Ram K; Nilvebrant, Johan; Eriksson, Olof; Tolmachev, Vladimir; Nestor, Marika V

    2016-02-01

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodistribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using

  19. Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma

    PubMed Central

    HAYLOCK, ANNA-KARIN; SPIEGELBERG, DIANA; MORTENSEN, ANJA C.; SELVARAJU, RAM K.; NILVEBRANT, JOHAN; ERIKSSON, OLOF; TOLMACHEV, VLADIMIR; NESTOR, MARIKA V.

    2016-01-01

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodis-tribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using

  20. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  1. Squamous cell carcinoma

    Cancer.gov

    The hallmarks of squamous cell carcinoma are the differentiation features of the squamous epithelium: keratinization and intercellular bridges. Large central masses of keratin, individual cell keratinization, and/or keratin pearls may form. Necrosis of tumor cell nests and accumulation of acute inflammatory cells are frequent features of poorly differentiated squamous cell carcinoma.

  2. p53 immunolabeling in archival paraffin-embedded tissues: optimal protocol based on microwave heating for eight antibodies on lung carcinomas.

    PubMed

    Tenaud, C; Negoescu, A; Labat-Moleur, F; Legros, Y; Soussi, T; Brambilla, E

    1994-10-01

    The prognostic value of p53 gene mutations is dealt with by several recent reports. However, retrospective assessment of p53 tumor status on archived samples has been prevented by p53 epitope alteration during routine fixation and embedding procedures. This study aimed at establishing a reproducible low-cost protocol to retrieve not only N-terminal, but also midregion and C-terminal, epitopes, with special attention to possible artifacts induced by epitope retrieval procedures. Using microwave heating, we compared the epitope retrieval efficiency of five solutions with eight commercial antibodies on 21 lung carcinomas for which frozen tissue and samples fixed with formalin and Bouin's liquid were available. All eight epitopes were retrieved, citrate buffer proving efficient for seven. PAb 240 epitope was restored by target unmasking fluid only. No false positivity was observed. Fixation-induced loss of p53 immunoreactivity was minimal for formalin (two of 10 tumors for one antibody each), more significant for Bouin (six of 10 tumors for one to five antibodies). On the other hand, staining intensity was maintained or even improved, and nonspecific staining reduced, through fixation. We conclude that p53 stabilization can be detected on routinely processed archival tumor samples with a reliability similar to that of frozen tissue by means of a microwave-based procedure and a panel of at least three antibodies, with epitopes on the N-terminal, C-terminal, and midpart of the molecule.

  3. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection: A STROBE-Compliant Article.

    PubMed

    Fu, Yi-Peng; Ni, Xiao-Chun; Yi, Yong; Cai, Xiao-Yan; He, Hong-Wei; Wang, Jia-Xing; Lu, Zhu-Feng; Han, Xu; Cao, Ya; Zhou, Jian; Fan, Jia; Qiu, Shuang-Jian

    2016-02-01

    As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature.In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone.IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID:26886627

  4. Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas

    PubMed Central

    Veracini, Laurence; Grall, Dominique; Schaub, Sébastien; Divonne, Stéphanie Beghelli-de la Forest; Etienne-Grimaldi, Marie-Christine; Milano, Gérard; Bozec, Alexandre; Babin, Emmanuel; Sudaka, Anne; Thariat, Juliette; Van Obberghen-Schilling, Ellen

    2015-01-01

    EGF receptor (EGFR) overexpression is thought to drive head and neck carcinogenesis however clinical responses to EGFR-targeting agents have been modest and alternate targets are actively sought to improve results. Src family kinases (SFKs), reported to act downstream of EGFR are among the alternative targets for which increased expression or activity in epithelial tumors is commonly associated to the dissolution of E-cadherin-based junctions and acquisition of a mesenchymal-like phenotype. Robust expression of total and activated Src was observed in advanced stage head and neck tumors (N=60) and in head and neck squamous cell carcinoma lines. In cultured cancer cells Src co-localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419 was both constitutive and independent of EGFR activation. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes. These findings reveal an EGFR-independent role for SFKs in the maintenance of intercellular junctions, which likely contributes to the cohesive invasion E-cadherin-positive cells in advanced tumors. Further, they highlight the need for a deeper comprehension of molecular pathways that drive collective cell invasion, in absence of mesenchymal transition, in order to combat tumor spread. PMID:25779657

  5. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined. PMID:27575269

  6. Proteomic differences between hepatocellular carcinoma and nontumorous liver tissue investigated by a combined gel-based and label-free quantitative proteomics study.

    PubMed

    Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Ahrens, Maike; Naboulsi, Wael; Weber, Frank; Hoffmann, Andreas-Claudius; Stephan, Christian; Kuhlmann, Katja; Eisenacher, Martin; Schlaak, Jörg F; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2013-07-01

    Proteomics-based clinical studies have been shown to be promising strategies for the discovery of novel biomarkers of a particular disease. Here, we present a study of hepatocellular carcinoma (HCC) that combines complementary two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography (LC-MS)-based approaches of quantitative proteomics. In our proteomic experiments, we analyzed a set of 14 samples (7 × HCC versus 7 × nontumorous liver tissue) with both techniques. Thereby we identified 573 proteins that were differentially expressed between the experimental groups. Among these, only 51 differentially expressed proteins were identified irrespective of the applied approach. Using Western blotting and immunohistochemical analysis the regulation patterns of six selected proteins from the study overlap (inorganic pyrophosphatase 1 (PPA1), tumor necrosis factor type 1 receptor-associated protein 1 (TRAP1), betaine-homocysteine S-methyltransferase 1 (BHMT)) were successfully verified within the same sample set. In addition, the up-regulations of selected proteins from the complements of both approaches (major vault protein (MVP), gelsolin (GSN), chloride intracellular channel protein 1 (CLIC1)) were also reproducible. Within a second independent verification set (n = 33) the altered protein expression levels of major vault protein and betaine-homocysteine S-methyltransferase were further confirmed by Western blots quantitatively analyzed via densitometry. For the other candidates slight but nonsignificant trends were detectable in this independent cohort. Based on these results we assume that major vault protein and betaine-homocysteine S-methyltransferase have the potential to act as diagnostic HCC biomarker candidates that are worth to be followed in further validation studies.

  7. Is local resection sufficient for parathyroid carcinoma?

    PubMed Central

    Basceken, Salim Ilksen; Genc, Volkan; Ersoz, Siyar; Sevim, Yusuf; Celik, Suleyman Utku; Bayram, Ilknur Kepenekci

    2015-01-01

    OBJECTIVES: Parathyroid carcinoma is a rare malignant disease of the parathyroid glands that appears in less than 1% of patients with primary hyperparathyroidism. In the literature, the generally recommended treatment is en bloc tumor excision with ipsilateral thyroid lobectomy. Based on our 12 years of experience, we discuss the necessity of performing thyroid lobectomy on parathyroid carcinoma patients. RESULTS: Eleven parathyroid carcinoma cases were included in the study. All operations were performed at the Department of Endocrine Surgery at Ankara University Medical School. Seven of the patients were male (63.6%), and the mean patient age was 48.9 ± 14.0 years. Hyperparathyroidism was the most common indication for surgery (n ϝ 10, 90.9%). Local disease was detected in 5 patients (45.5%), invasive disease was detected in 5 patients (45.5%) and metastatic disease was detected in 1 patient (9.1%). The mean follow-up period was 99.6 ± 42.1 months, and the patients' average disease-free survival was 96.0 ± 49.0 months. During the follow-up period, only 1 patient died of metastatic parathyroid carcinoma. CONCLUSION: Parathyroid carcinoma has a slow-growing natural progression, and regional lymph node metastases are uncommon. Although our study comprised few patients, it nevertheless showed that in selected cases, parathyroid carcinoma could be solely treated with parathyroidectomy. PMID:26017790

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

    PubMed

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

    2010-11-01

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

  9. Epidemiology of bronchioloalveolar carcinoma.

    PubMed

    Falk, R T; Pickle, L W; Fontham, E T; Greenberg, S D; Jacobs, H L; Correa, P; Fraumeni, J F

    1992-01-01

    Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.

  10. Decision Based on Narrow Band Imaging Cystoscopy without a Referential Normal Standard Rather Increases Unnecessary Biopsy in Detection of Recurrent Bladder Urothelial Carcinoma Early after Intravesical Instillation

    PubMed Central

    Song, Phil Hyun; Cho, Seok; Ko, Young Hwii

    2016-01-01

    Purpose The purpose of this study was to calculate the operating characteristics of narrowband imaging (NBI) cystoscopy versus traditional white light cystoscopy (WLC) in common clinical scenarios involving suspicion of bladder urothelial carcinoma (UC). Materials and Methods Sixty-three consecutive patients initially underwent WLC and then NBI in a single session for evaluation of microscopic hematuria (group I, n=20), gross hematuria (group II, n=19), and follow-up for prior UC (group III, n=24), by an experienced urologist. All lesions that were abnormal in contrast with adjacent normal mucosa were diagnosed as positive and biopsied. Results Sixty-six biopsies from 47 patients were performed. Pathologic examination showed 17 cases of UC from 21 sites. While the overall sensitivity of NBI was similar to that of WLC (100% vs. 94.1%), the specificity of NBI was significantly lower than that of WLC (50% vs. 86.9%, p < 0.001), particularly in group III (38.9% vs. 88.9%, p=0.004). Based on identification by NBI only, 23 additional biopsies from 18 cases were performed for identification of one patient with UC, who belonged to group III. In this group, to identify this specific patient, 15 additional biopsies were performed from 10 patients. All seven cases with positive findings from NBI within 2 months after the last intravesical therapy were histologically proven as negative. Conclusion In evaluation for recurrence early after intravesical instillation, the decision based on NBI increased unnecessary biopsy in the absence of an established standard for judging NBI. PMID:25761489

  11. A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2016-01-01

    Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately. PMID:26918446

  12. Exploration and Validation of C-Reactive Protein/Albumin Ratio as a Novel Inflammation-Based Prognostic Marker in Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Yuan; Zhou, Guan-Qun; Liu, Xu; Chen, Lei; Li, Wen-Fei; Tang, Ling-Long; Liu, Qing; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The prognostic value of C-reactive protein/albumin ratio (CRP/Alb), a novel inflammation-based marker, remains unknown in nasopharyngeal carcinoma (NPC). Methods: We conducted a retrospective review of 1572 consecutive patients with non-metastatic NPC. Patients were randomly divided into a training set (n = 514) and validation set (n = 1058). The prognostic value of the CRP/Alb ratio and the modified Glasgow prognostic score (mGPS; a well-recognized inflammation-based score) was assessed. Results: Receiver-operating characteristic analysis identified 0.05 as the optimal CRP/Alb cut-off value for disease failure in the training set. Patients with a CRP/Alb > 0.05 had poorer overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the training set (all P < 0.05). These results were confirmed in the validation set (all P < 0.05) and the whole cohort (all P < 0.001). In multivariate analysis of the entire cohort, the pretreatment CRP/Alb ratio was an independent prognostic factor for OS (HR, 1.394; 95% CI, 1.004-1.937; P = 0.048) and DMFS (HR, 1.545; 95% CI, 1.124-2.122; P = 0.007), but not for DFS (P = 0.083). The mGPS had no significant independent prognostic value for any end-point. Conclusion: CRP/Alb ratio is an useful prognostic indicator in patients with NPC, independent of disease stage. PMID:27471556

  13. Low-grade adenosquamous carcinoma of the breast: imaging and histopathologic characteristics of this rare disease.

    PubMed

    Scali, Elena P; Ali, Rola H; Hayes, Malcolm; Tyldesley, Scott; Hassell, Patricia

    2013-11-01

    Low-grade adenosquamous carcinoma is a rare histologic subtype of breast carcinoma that has a variable mammographic and sonographic appearance, which overlaps with both benign and malignant neoplasms. Because of its lack of unique imaging features, a diagnosis of low-grade adenosquamous carcinoma is based on histopathology. The recognition of this entity is an important consideration in the differential diagnosis of breast masses and carries implications for prognosis, which is more favorable than other types of breast carcinoma.

  14. Do All Patients of Breast Carcinoma Need 3-Dimensional CT-Based Planning? A Dosimetric Study Comparing Different Breast Sizes

    SciTech Connect

    Munshi, Anusheel Pai, Rajeshri H.; Phurailatpam, Reena; Budrukkar, Ashwini; Jalali, Rakesh; Sarin, Rajiv; Deshpande, D.D.; Shrivastava, Shyam K.; Dinshaw, Ketayun A.

    2009-07-01

    Evaluation of dose distribution in a single plane (i.e., 2-dimensional [2D] planning) is simple and less resource-intensive than CT-based 3-dimensional radiotherapy (3DCRT) planning or intensity modulated radiotherapy (IMRT). The aim of the study was to determine if 2D planning could be an appropriate treatment in a subgroup of breast cancer patients based on their breast size. Twenty consecutive patients who underwent breast conservation were planned for radiotherapy. The patients were grouped in 3 different categories based on their respective chest wall separation (CWS) and the thickness of breast, as 'small,' 'medium,' and 'large.' Two more contours were taken at locations 5 cm superior and 5 cm inferior to the isocenter plane. Maximum dose recorded at specified points was compared in superior/inferior slices as compared to the central slice. The mean difference for small breast size was 1.93 (standard deviation [SD] = 1.08). For medium breas size, the mean difference was 2.98 (SD = 2.40). For the large breasts, the mean difference was 4.28 (SD = 2.69). Based on our dosimetric study, breast planning only on the single isocentric contour is an appropriate technique for patients with small breasts. However, for large- and medium-size breasts, CT-based planning and 3D planning have a definite role. These results can be especially useful for rationalizing treatment in busy oncology centers.

  15. Technical considerations in brachytherapy boost for a case of squamous cell carcinoma of the external auditory canal based on our case.

    PubMed

    Ilangovan, Bhargavi; Stumpf, Janos; Murali, V; Sasikumar, Neetu; Devi, Rathna

    2015-01-01

    Squamous cell carcinoma of the external auditory canal is a rare entity. The patients present with ear discharge and otalgia. They are treated with radiotherapy and surgery. Surgery with oncological priorities is quite complex with substantial consequences. We are reporting a patient with squamous cell carcinoma of the external auditory canal, who was treated with limited surgery followed by radiotherapy. Radiotherapy was a combination of external beam radiotherapy and brachytherapy. High dose rate brachytherapy was given using an ear speculum fixed with wax and a suction catheter. This article is to highlight the technique and dosimetry of the brachytherapy procedure. PMID:26458716

  16. Comparative analysis of SmartArc-based dual arc volumetric-modulated arc radiotherapy (VMAT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma.

    PubMed

    Lee, Tsair-Fwu; Chao, Pei-Ju; Ting, Hui-Min; Lo, Su-Hua; Wang, Yu-Wen; Tuan, Chiu-Ching; Fang, Fu-Min; Su, Te-Jen

    2011-11-15

    The purpose of this study was to evaluate and quantify the planning performance of SmartArc-based volumetric-modulated arc radiotherapy (VMAT) versus fixed-beam intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) using a sequential mode treatment plan. The plan quality and performance of dual arc-VMAT (DA-VMAT) using the Pinnacle3 Smart-Arc system (clinical version 9.0; Philips, Fitchburg, WI, USA) were evaluated and compared with those of seven-field (7F)-IMRT in 18 consecutive NPC patients. Analysis parameters included the conformity index (CI) and homogeneity index (HI) for the planning target volume (PTV), maximum and mean dose, normal tissue complication probability (NTCP) for the specified organs at risk (OARs), and comprehensive quality index (CQI) for an overall evaluation in the 11 OARs. Treatment delivery time, monitor units per fraction (MU/fr), and Gamma(3 mm, 3%) evaluations were also analyzed. DA-VMAT achieved similar target coverage and slightly better homogeneity than conventional 7F-IMRT with a similar CI and HI. NTCP values were only significantly lower in the left parotid gland (for xerostomia) for DA-VMAT plans. The mean value of CQI at 0.98 ± 0.02 indicated a 2% benefit in sparing OARs by DA-VMAT. The MU/fr used and average delivery times appeared to show improved efficiencies in DA-VMAT. Each technique demonstrated high accuracy in dose delivery in terms of a high-quality assurance (QA) passing rate (> 98%) of the Gamma(3 mm, 3%) criterion. The major difference between DA-VMAT and 7F-IMRT using a sequential mode for treating NPC cases appears to be improved efficiency, resulting in a faster delivery time and the use of fewer MU/fr.

  17. Anti-tuberculosis treatments and risk of hepatocellular carcinoma in tuberculosis patients with liver cirrhosis: a population-based case-control study.

    PubMed

    Lim, Y-P; Lin, C-L; Hung, D-Z; Lin, Y-N; Kao, C-H

    2015-03-01

    The objective of this study was to evaluate the association between the use of anti-tuberculosis (anti-TB) agents, isoniazid (INH), rifampicin (RIF), and their combination (INH + RIF), and the risk of hepatocellular carcinoma (HCC) in cirrhotic patients. This population-based case-control study was conducted using a research database of Taiwan's National Health Insurance program. Cirrhotic patients first diagnosed with HCC between 1996 and 2011 (n = 50,351), among whom 4,738 were anti-TB medication users, were evaluated. Cirrhotic patients who did not develop HCC within the same period, frequency-matched according to age, sex, and index year, were evaluated as the control group (n = 47,488). The adjusted odds ratio (OR) of HCC was 1.34 [95 % confidence interval (CI), 1.20-1.50] in INH + RIF users compared with non-INH + RIF users. Long-term (>12 months) use of INH, RIF, and INH + RIF was significantly associated with increased risk of HCC, with an adjusted OR of 3.51 (95 % CI, 2.11-5.84), 4.17 (95 % CI, 2.76-4.31), and 7.17 (95 % CI, 4.08-12.6), respectively, after adjusting for age, sex, and comorbidities. An average dose of INH + RIF >16,050 mg/year was associated with increased risk of HCC in cirrhotic patients, with an adjusted OR of 1.48 (95 % CI, 1.27-1.73). Our results indicate that cirrhotic patients with long-term or high-dose INH and RIF treatment, particularly their combination, are associated with increased risk of HCC development.

  18. Maintenance monotherapy with Gemcitabine following cisplatin-based primary combination chemotherapy in surgically treated advanced urothelial carcinoma: A matched-pair single institution analysis

    PubMed Central

    KALOGIROU, CHARIS; SVISTUNOV, ANDREY; KREBS, MARKUS; LAUSENMEYER, EVA MARIA; VERGHO, DANIEL; RIEDMILLER, HUBERTUS; KOCOT, ARKADIUS

    2016-01-01

    The role of maintenance therapy with Gemcitabine (GEM) following cisplatin-based combination chemotherapy (CBCC) in patients with surgically treated advanced urothelial carcinoma (UC) remains to be fully elucidated. In the present case control study, a retrospective analysis was performed to evaluate the role of GEM monotherapy following surgical intervention for advanced UC. Between 1999 and 2013, 38 patients were identified with surgically treated advanced UC after having completed CBCC, who were additionally treated quarterly with two consecutive GEM (1,250 mg/m2) infusions as maintenance therapy. This collective was matched by propensity score matching to a control collective (n=38) that received primary CBCC alone, and the overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) rates were determined for the two collectives using Kaplan-Meier estimates and the log-rank test. Regression analysis was performed using the Cox proportional hazards model. The median follow-up time was 37 months (interquartile range: 9–148). Interestingly, patients treated with GEM following primary chemotherapy had a significantly improved outcome with respect to the 5-year OS (46.2 vs. 26.4%, P=0.0314) and 5-year CSS (61.3 vs. 33.4%, P=0.0386) rates. Notably, the 5-year PFS rate did not differ between the two groups (10.3 vs. 16.1%, P=0.134). It is proposed that additional GEM maintenance monotherapy is able to improve survival rates following primary CBCC in surgically treated patients with advanced UC, suggesting a possible treatment option for patients with, e.g., unclear disease status, or those who would require an active maintenance therapy in the future. Prospective studies should further determine the impact of GEM monotherapy with respect to PFS rates in groups comprising larger numbers of patients. PMID:27073682

  19. GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy

    PubMed Central

    Hu, Danrong; Mezghrani, Omar; Zhang, Lei; Chen, Yi; Ke, Xue; Ci, Tianyuan

    2016-01-01

    Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs. PMID:27785019

  20. Intravoxel incoherent motion model–based analysis of diffusion-weighted magnetic resonance imaging with 3 b-values for response assessment in locoregional therapy of hepatocellular carcinoma

    PubMed Central

    Mürtz, Petra; Penner, Arndt-Hendrik; Pfeiffer, Anne-Kristina; Sprinkart, Alois M; Pieper, Claus C; König, Roy; Block, Wolfgang; Schild, Hans H; Willinek, Winfried A; Kukuk, Guido M

    2016-01-01

    Purpose The aim of this study was to evaluate an intravoxel incoherent motion (IVIM) model–based analysis of diffusion-weighted imaging (DWI) for assessing the response of hepatocellular carcinoma (HCC) to locoregional therapy. Patients and methods Respiratory-gated DWI (b=0, 50, and 800 s/mm2) was retrospectively analyzed in 25 patients who underwent magnetic resonance imaging at 1.5 T before and 6 weeks following the first cycle of transarterial chemoembolization therapy, transarterial ethanol-lipiodol embolization therapy, and transarterial radioembolization therapy. In addition to the determination of apparent diffusion coefficient, ADC(0,800), an estimation of the diffusion coefficient, D′, and the perfusion fraction, f′, was performed by using a simplified IVIM approach. Parameters were analyzed voxel-wise. Tumor response was assessed in a central slice by using a region of interest (ROI) covering the whole tumor. HCCs were categorized into two groups, responders and nonresponders, according to tumor size changes on first and second follow ups (if available) and changes of contrast-enhanced region on the first follow up. Results In total, 31 HCCs were analyzed: 17 lesions were assigned to responders and 14 were to nonresponders. In responders, ADC(0,800) and D′ were increased after therapy by ~30% (P=0.00004) and ~42% (P=0.00001), respectively, whereas f′ was decreased by ~37% (P=0.00094). No significant changes were found in nonresponders. Responders and nonresponders were better differentiated by changes in D′ than by changes in ADC(0,800) (area under the curve =0.878 vs 0.819 or 0.714, respectively). Conclusion In patients with HCCs undergoing embolization therapy, diffusion changes were better reflected by D′ than by conventional ADC(0,800), which is influenced by counteracting perfusion changes as assessed by f′. PMID:27799790

  1. Outcomes of xerostomia-related quality of life for nasopharyngeal carcinoma treated by IMRT: based on the EORTC QLQ-C30 and H&N35 questionnaires.

    PubMed

    Bian, Xiuhua; Song, Tao; Wu, Shixiu

    2015-01-01

    The aim of this study was to review the published literature addressing the question of whether intensity-modulated radiotherapy (IMRT) resulted in an improvement of quality of life (QoL), especially xerostomia-related QoL of all nasopharyngeal carcinoma patients as time progressed. A literature search of PubMed, Embase and Google Scholar was performed, only reports containing original data of the QoL scores after treated by IMRT were included. Two independent reviewers extracted information of study design, study population, interventions, outcome measures and conclusions for each article. The inclusion criteria were met by 14 articles covering outcomes based on the questionnaires treated by IMRT. Data from same questionnaires (European Organization of Research and Treatment of Cancer QLQ-C30 and H&N35 questionnaires) were exacted and we analyzed four items (global health status, dry mouth and sticky saliva, swallowing, social eating and social contact), which have a close relationship with xerostomia-related QoL. Results indicated that a maximal deterioration of most QoL scales including global health status developed during treatment or at the end of the treatment course and then followed by a gradual recovery to 1 year, 1-2 years after IMRT, compared with their baseline level, some specific head and neck items, most in the EORTC QLQ H&N35, remained worse for the surviving patients. In conclusion, the published data reasonably support the benefits of IMRT in improving QoL, but xerostomia-related items still had a significantly negative effect in 2 years to impact a survivor's QoL.

  2. Observations on continuously growing roots of the sloth and the K14-Eda transgenic mice indicate that epithelial stem cells can give rise to both the ameloblast and root epithelium cell lineage creating distinct tooth patterns.

    PubMed

    Tummers, Mark; Thesleff, Irma

    2008-01-01

    Root development is traditionally associated with the formation of Hertwig's epithelial root sheath (HERS), whose fragments give rise to the epithelial cell rests of Malassez (ERM). The HERS is formed by depletion of the core of stellate reticulum cells, the putative stem cells, in the cervical loop, leaving only a double layer of the basal epithelium with limited growth capacity. The continuously growing incisor of the rodent is subdivided into a crown analog half on the labial side, with a cervical loop containing a large core of stellate reticulum, and its progeny gives rise to enamel producing. The lingual side is known as the root analog and gives rise to ERM. We show that the lingual cervical loop contains a small core of stellate reticulum cells and suggest that it acts as a functional stem cell niche. Similarly we show that continuously growing roots represented by the sloth molar and K14-Eda transgenic incisor maintain a cervical loop with a small core of stellate reticulum cells around the entire circumference of the tooth and do not form a HERS, and still give rise to ERM. We propose that HERS is not a necessary structure to initiate root formation. Moreover, we conclude that crown vs. root formation, i.e. the production of enamel vs. cementum, and the differentiation of the epithelial cells into ameloblasts vs. ERM, can be regulated independently from the regulation of stem cell maintenance. This developmental flexibility may underlie the developmental and evolutionary diversity in tooth patterning.

  3. Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

    PubMed

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacéra; Guigay, Joël; Janot, François; Temam, Stéphane; Daly-Schveitzer, Nicolas; Bourhis, Jean; Tao, Yungan

    2014-11-01

    To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

  4. Gastric Large Cell Neuroendocrine Carcinoma

    PubMed Central

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    with a platinum-based regimen. Discussion: In the current WHO classification of gastric tumors, only carcinoids and small cell carcinomas are included in the neuroendocrine (NE) tumor category. However, a new pathologic entity has recently been described by Jiang et al. High-grade gastric NE carcinomas of non-small cell type have been tentatively named large cell neuroendocrine carcinomas (LCNEC). Morphologically, these tumors differ from both carcinoids and small cell carcinomas, and are confirmed immunohistochemically using NE markers, chromogranin-A and synaptophysin. Gastric LCNEC is currently defined if > 50% of tumor cells demonstrate positivity for chromogranin-A and/or synaptophysin. LCNECs account for < 1.5% of all gastric cancers. LCNECs, which had been previously diagnosed as adenocarcinomas (ACs) are highly malignant and portend a significantly worse prognosis than ACs. Reported 5-year survival rates for LCNECs and ACs have are 31.1% and 69.3%, respectively. At the time of presentation, 70–75% of LCNECs have lymph node metastases and 5–10% also have metastases to liver. Clinical management of gastric LCNECs has not been clearly defined given the rarity of the malignancy and limited experience in its management. An overall regression rate of 67% was achieved in a small series of poorly differentiated gastroenteropancreatic NE carcinomas treated with cisplatin and etoposide.

  5. Stages of Adrenocortical Carcinoma

    MedlinePlus

    ... of Childhood Treatment for more information.) Having certain genetic conditions increases the risk of adrenocortical carcinoma. Anything ... can be a sign of disease. CT scan (CAT scan) : A procedure that makes a series of ...

  6. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  7. Colorectal carcinoma: Pathologic aspects

    PubMed Central

    Fleming, Matthew; Ravula, Sreelakshmi; Tatishchev, Sergei F.

    2012-01-01

    Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance. PMID:22943008

  8. Cholescintigraphy in gallbladder carcinoma

    SciTech Connect

    Colletti, P.M.; Ralls, P.W.; Siegel, M.E.; Halls, J.M.

    1986-04-01

    Findings on cholescintigraphy in gallbladder carcinoma are described in five patients. Four patients presenting with acute cholecystitis had nonvisualization of the gallbladder with normal hepatoenteric transit time. One of these had a large portal mass and two had liver metastasis as additional findings. The fifth patient was jaundiced, and showed absence of bowel activity compatible with total biliary obstruction. Both the clinical and scintigraphic findings in gallbladder carcinoma are difficult to separate from findings in cholelithiasis and cholecystitis.

  9. [Pulmonary sarcomatoid carcinoma].

    PubMed

    Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

    2016-01-01

    Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics.

  10. Suggestions for Lymph Node Classification of UICC/AJCC Staging System: A Retrospective Study Based on 1197 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiation Therapy

    PubMed Central

    Guo, Qiaojuan; Pan, Jianji; Zong, Jingfeng; Zheng, Wei; Zhang, Chun; Tang, Linbo; Chen, Bijuan; Cui, Xiaofei; Xiao, Youping; Chen, Yunbin; Lin, Shaojun

    2015-01-01

    Abstract This article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era. A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified. Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%). Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N

  11. The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma

    PubMed Central

    Shen, Er-Dong; Liu, Bo; Yu, Xin-Shuang; Xiang, Zhen-Fei; Huang, Hui-Yun

    2016-01-01

    Objective The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). Methods A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. Results miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates

  12. [Changes in the clinical picture of laryngeal carcinoma in the last 15 years based on material from the Otolaryngology Department of the District Hospital in Kielce].

    PubMed

    Zyłka, S; Mezyk, R; Siudowska, U; Bień, S

    1995-01-01

    The 659 cases of laryngeal carcinoma treated by surgery from 1980 to 1994 was taken into analysis. The modification of age, sex, primary localisation and clinical advancement of disease was analysed. The significant increase highly advanced cases was pointed out, as a main factor influencing the treatment results.

  13. Evaluation of multiple image-based modalities for image-guided radiation therapy (IGRT) of prostate carcinoma: A prospective study

    SciTech Connect

    Mayyas, Essa; Chetty, Indrin J.; Chetvertkov, Mikhail; Wen, Ning; Neicu, Toni; Nurushev, Teamor; Ren Lei; Pradhan, Deepak; Movsas, Benjamin; Elshaikh, Mohamed A.; Lu Mei; Stricker, Hans

    2013-04-15

    Purpose: Setup errors and prostate intrafraction motion are main sources of localization uncertainty in prostate cancer radiation therapy. This study evaluates four different imaging modalities 3D ultrasound (US), kV planar images, cone-beam computed tomography (CBCT), and implanted electromagnetic transponders (Calypso/Varian) to assess inter- and intrafraction localization errors during intensity-modulated radiation therapy based treatment of prostate cancer. Methods: Twenty-seven prostate cancer patients were enrolled in a prospective IRB-approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall, 1100 fractions were evaluated. For each fraction, treatment targets were localized using US, kV planar images, and CBCT in a sequence defined to determine setup offsets relative to the patient skin tattoos, intermodality differences, and residual errors for each patient and patient cohort. Planning margins, following van Herk's formalism, were estimated based on error distributions. Calypso-based localization was not available for the first eight patients, therefore centroid positions of implanted gold-seed markers imaged prior to and immediately following treatment were used as a motion surrogate during treatment. For the remaining 19 patients, Calypso transponders were used to assess prostate intrafraction motion. Results: The means ({mu}), and standard deviations (SD) of the systematic ({Sigma}) and random errors ({sigma}) of interfraction prostate shifts (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and US, averaged over all patients and fractions, were: [{mu}{sub CBCT}= (-1.2, 0.2, 1.1) mm, {Sigma}{sub CBCT}= (3.0, 1.4, 2.4) mm, {sigma}{sub CBCT}= (3.2, 2.2, 2.5) mm], [{mu}{sub kV}= (-2.9, -0.4, 0.5) mm, {Sigma}{sub kV}= (3.4, 3.1, 2.6) mm, {sigma}{sub kV}= (2.9, 2.0, 2.4) mm], and [{mu}{sub US}= (-3.6, -1.4, 0.0) mm, {Sigma}{sub US}= (3.3, 3.5, 2.8) mm, {sigma}{sub US}= (4.1, 3.8, 3.6) mm], in the anterior

  14. A Study of Basal Cell Carcinoma in South Asians for Risk Factor and Clinicopathological Characterization: A Hospital Based Study

    PubMed Central

    Mahajan, Bharat Bhushan; Kaur, Sandeep; Yadav, Ashish; Singh, Navtej; Singh, Amarbir

    2014-01-01

    Objectives. Although the incidence of skin cancers in India (part of South Asia) is low, the absolute number of cases may be significant due to large population. The existing literature on BCC in India is scant. So, this study was done focusing on its epidemiology, risk factors, and clinicopathological aspects. Methods. A hospital based cross-sectional study was conducted in Punjab, North India, from 2011 to 2013. History, examination and histopathological confirmation were done in all the patients visiting skin department with suspected lesions. Results. Out of 36 confirmed cases, 63.9% were females with mean ± SD age being 60.9 ± 14.2 years. Mean duration of disease was 4.7 years. Though there was statistically significant higher sun exposure in males compared to females (P value being 0.000), BCC was commoner in females, explainable by intermittent sun exposure (during household work in the open kitchens) in women. Majority of patients (88.9%) had a single lesion. Head and neck region was involved in 97.2% of cases, with nose being the commonest site (50%) with nodular/noduloulcerative morphology in 77.8% of cases. Pigmentation was evident in 22.2% of cases clinically. Nodular variety was the commonest histopathological variant (77.8%). Conclusions. This study highlights a paradoxically increasing trend of BCC with female preponderance, preferential involvement of nose, and higher percentage of pigmentation in Indians. PMID:25530883

  15. The Emerging Molecular Landscape of Urothelial Carcinoma.

    PubMed

    Solomon, James P; Hansel, Donna E

    2016-09-01

    Although there have been many recent discoveries in the molecular alterations associated with urothelial carcinoma, current understanding of this disease lags behind many other malignancies. Historically, a two-pathway model had been applied to distinguish low- and high-grade urothelial carcinoma, although significant overlap and increasing complexity of molecular alterations has been recently described. In many cases, mutations in HRAS and FGFR3 that affect the MAPK and PI3K pathways seem to be associated with noninvasive low-grade papillary tumors, whereas mutations in TP53 and RB that affect the G1-S transition of the cell cycle are associated with high-grade in situ and invasive carcinoma. However, recent large-scale analyses have identified overlap in these pathways relative to morphology, and in addition, many other variants in a wide variety of oncogenes and tumor-suppressor genes have been identified. New technologies including next-generation sequencing have enabled more detailed analysis of urothelial carcinoma, and several groups have proposed molecular classification systems based on these data, although consensus is elusive. This article reviews the current understanding of alterations affecting oncogenes and tumor-suppressor genes associated with urothelial carcinoma, and their application in the context of morphology and classification schema. PMID:27523968

  16. Therapeutic challenges in renal cell carcinoma

    PubMed Central

    Penticuff, Justin C; Kyprianou, Natasha

    2015-01-01

    Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of “targeted therapies”. Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states. This review discusses the current understanding of diagnostic challenges and the mechanism-based clinical evidence on therapeutic management of advanced RCC. PMID:26309897

  17. [Merkel cell skin carcinoma].

    PubMed

    Krejcí, K; Zadrazil, J; Tichý, T; Horák, P; Ciferská, H; Hodulová, M; Zezulová, M; Zlevorová, M

    2010-01-01

    Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin

  18. Current management of ductal carcinoma in situ.

    PubMed

    Barth, A; Brenner, R J; Giuliano, A E

    1995-10-01

    Ductal carcinoma in situ represents a biologically and histologically heterogeneous group of lesions characterized by the proliferation of neoplastic epithelial cells confined to the ducts of the breast. Before screening mammography, ductal carcinoma in situ was considered uncommon; patients were usually diagnosed by a breast mass or bloody nipple discharge, and their treatment was mastectomy. Today it represents 20% to 30% of mammographically detected breast cancers and 10% to 15% of all diagnosed breast cancers in the United States. The invariable progression of this cancer to invasive breast cancer requiring mastectomy has been challenged, but because most patients have been treated with mastectomy, knowledge about ductal carcinoma in situ is limited and primarily based on retrospective data. Further insight will emerge from randomized prospective studies that are near completion. Currently available data indicate that breast-conserving treatments are valid alternatives to mastectomy for most patients with this disease. PMID:7483593

  19. 3-D reconstruction and virtual ductoscopy of high-grade ductal carcinoma in situ of the breast with casting type calcifications using refraction-based X-ray CT.

    PubMed

    Ichihara, Shu; Ando, Masami; Maksimenko, Anton; Yuasa, Tetsuya; Sugiyama, Hiroshi; Hashimoto, Eiko; Yamasaki, Katsuhito; Mori, Kensaku; Arai, Yoshinori; Endo, Tokiko

    2008-01-01

    Stereomicroscopic observations of thick sections, or three-dimensional (3-D) reconstructions from serial sections, have provided insights into histopathology. However, they generally require time-consuming and laborious procedures. Recently, we have developed a new algorithm for refraction-based X-ray computed tomography (CT). The aim of this study is to apply this emerging technology to visualize the 3-D structure of a high-grade ductal carcinomas in situ (DCIS) of the breast. The high-resolution two-dimensional images of the refraction-based CT were validated by comparing them with the sequential histological sections. Without adding any contrast medium, the new CT showed strong contrast and was able to depict the non-calcified fine structures such as duct walls and intraductal carcinoma itself, both of which were barely visible in a conventional absorption-based CT. 3-D reconstruction and virtual endoscopy revealed that the high-grade DCIS was located within the dichotomatous branches of the ducts. Multiple calcifications occurred in the necrotic core of the continuous DCIS, resulting in linear and branching (casting type) calcifications, a hallmark of high-grade DCIS on mammograms. In conclusion, refraction-based X-ray CT approaches the low-power light microscopic view of the histological sections. It provides high quality slice data for 3-D reconstruction and virtual ductosocpy.

  20. Male breast carcinoma: a clinicopathological and immunohistochemical characterization study.

    PubMed

    Zhou, Ruoji; Yu, Lin; Zhou, Shuling; Bi, Rui; Shui, Ruohong; Yu, Baohua; Lu, Hongfen; Cai, Xu; Yang, Wentao

    2014-01-01

    Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.

  1. Chyluria associated with bronchial carcinoma

    PubMed Central

    Morice, A. H.; Wood, J. R.

    1981-01-01

    Chylous pleural effusion, though not chyluria, is a recognized association of carcinoma of the bronchus. A case of chyluria associated with squamous bronchial carcinoma is reported. Chyluria in this patient was successfully treated by dietary modification. PMID:7329888

  2. Validation of T Stage According to Depth of Invasion and N Stage Subclassification Based on Number of Metastatic Lymph Nodes for Distal Extrahepatic Bile Duct (EBD) Carcinoma

    PubMed Central

    Moon, Ahrim; Choi, Dong Wook; Choi, Seoung Ho; Heo, Jin Seok; Jang, Kee-Taek

    2015-01-01

    Abstract According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: ≥ 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1–3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs ≥ 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more

  3. SU-E-J-111: The Contouring Error of the Parotids Based On the CT and MRI Images in Radiotherapy Planning for Nasopharyngeal Carcinoma

    SciTech Connect

    Gong, G; Liu, C

    2014-06-01

    Purpose: To analyze the variation of sketching the parotid for patients with nasopharyngeal carcinoma who underwent radiotherapy based on computed tomography (CT) and magnetic resonance(MR) images. Methods: 41 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. The Gross Tumor Volume and Organs at risk were contoured on both contrasted CT and T1-MR images. For each patient, one radiotherapist sketched the parotid on CT and MR images for 10 times, and 10 different radiotherapists were asked to sketching the parotid on CT and MR images only one time. The inter- and intra-observers volumes and outline variations were compared. Results: The volumes of parotid contoured by inter-observer on CT and MR images were 34.6±12.1cm{sup 3}(left),34.3±9.0cm{sup 3}(right) and 24.6±7.6cm{sup 3}(L),23.2±8.1cm{sup 3}(R); In the same way, for intra-observer on CT and MR images the volumes were 28.2±7.6cm{sup 3}(L),29.4±9.4cm{sup 3}(R) and 24.4±7.6cm{sup 3}(L),22.5±7.4cm{sup 3}(R), respectively. The variable ratios of volume on MR images were 4.7±0.7%(L),5.0±0.6%(R) for inter-observer and 2.3±0.4%(L),2.1±0.7%(R) for intra-observer. Similarly, The inter- and intra-observer ratios for contouring on CT images reached 18.0±4.8%(L),17.4±4.6%(R) and 6.3±1.5%(L),6.8±1.5%(R), respectively. Conclusion: Contouring the parotids on MR images was more accurate and reproducible than that on CT images.

  4. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.

    PubMed

    Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R; Voicu, Horatiu; Torres-Garcia, Wandaliz; Verhaak, Roel G W; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan

    2015-10-01

    Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the

  5. Primary pulmonary cavitating carcinomas

    PubMed Central

    Chaudhuri, M. Ray

    1973-01-01

    A primary lung cancer can produce a cavity in three ways. The first is `cavitary necrosis' due to breakdown of the growth itself. The second is `stenotic abscess' due to infection and breakdown of the lung parenchyma distal to bronchial obstruction caused by the growth. The third type is `spill-over abscess'. In the present series, necrosis and cavitation were observed in 100 cases out of a total of 632 primary bronchial carcinomas seen at the London Chest Hospital from July 1967 to June 1970. There were 91 males and nine females with an average age of 58·45 years. All except one smoked very heavily and had considerable symptoms. The size of the cavities ranged from 1 to 10 cm and their wall thickness from 0·5 to 3 cm. They were single in 92 cases and multiple (up to four) in eight. In 42 cases, the cancerous cavitation was central, in 38 intermediate, and in 20 peripheral. The segments most frequently affected were the apicoposterior segment of the left upper lobe and the superior segment of the left lower lobe. For descriptive purposes, these cavitating carcinomas were also divided into six broad groups on the basis of radiological and pathological correlations. Neoplastic cells in the sputum were found in 64 cases. Bronchoscopy revealed growth in 42 cases and biopsy was positive in 48. The main microscopic feature was vascular invasion of medium-sized muscular arteries and veins found in the vicinity of every cavitating bronchial carcinoma. Invasion along with tumour plugging of the vessels was observed in 75 cases and thrombosis alone in 55 cases. There were 82 squamous-cell carcinomas, 11 undifferentiated carcinomas of large polygonal-cell type, and seven adeno-alveolar cell carcinomas. The single most important and noteworthy feature in the present series was that oat-cell carcinoma hardly ever undergoes necrosis. Out of a total of 95 cases observed, only three showed necrosis, and this was minimal and characteristically devoid of cavitation. In oat

  6. Maxillary sinus carcinoma

    SciTech Connect

    Lee, F.; Ogura, J.H.

    1981-01-01

    Primary site control, anatomical site of failure, survival, and complications of treatment were determined in a retrospective review of primary maxillary sinus carcinoma. Sixty-one patients were treated by radiation followed by surgery and 35 by radiation alone. Primary tumor control was achieved in 69% of patients receiving combined treatment, 14% of patients treated with radiation alone, and 49% of all patients. Local control did not differ with histological type. Virtually all epidermoid and undifferentiated carcinoma recurrences occurred within 2 years, but 27% of adenocarcinomas recurred after 2 years.

  7. [Medullary thyroid carcinoma].

    PubMed

    Niccoli-Sire, P; Conte-Devolx, B

    2007-10-01

    Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery. PMID:17572372

  8. Hepatocellular carcinoma: a review

    PubMed Central

    Balogh, Julius; Victor, David; Asham, Emad H; Burroughs, Sherilyn Gordon; Boktour, Maha; Saharia, Ashish; Li, Xian; Ghobrial, R Mark; Monsour, Howard P

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated

  9. Predictors of disease progression in ductal carcinoma in situ of the breast and vascular patterns.

    PubMed

    Adler, Esther H; Sunkara, Jaya L; Patchefsky, Arthur S; Koss, Leopold G; Oktay, Maja H

    2012-04-01

    Breast carcinoma-induced angiogenesis helps meet growing metabolic needs of tumors and progressively increases with malignant transformation of benign ducts to ductal carcinoma in situ (DCIS) and ductal carcinoma in situ to invasive carcinoma. There are conflicting data regarding the difference in angiogenesis in low-, intermediate-, and high-grade ductal carcinoma in situ. If angiogenesis is related to ductal carcinoma in situ progression, the types of ductal carcinoma in situ with more aggressive biologic potential would have different vascular patterns than the less aggressive ones. In this study, we classified 51 cases of ductal carcinoma in situ as low (10-20 years to progression to invasive carcinoma), moderate, or high aggressive (2-5 years to progression to invasive carcinoma), based on criteria outlined by Tsikitis and Chung (Am J Clin Oncol 2006; 29:305), which takes into account nuclear grade, mitotic rate, Ki-67, Her2Neu, P53, estrogen, and progesterone receptor expression. We correlated these 3 groups of ductal carcinoma in situ with the extent of periductal and stromal vascularity and the presence and type of vascular breaks. No association of aggressive biologic behavior of ductal carcinoma in situ with any vascular pattern was found. Moreover, no correlation was found between vascular patterns and classifiers of aggressiveness, microvascular density, or outcome (local recurrence, invasive carcinoma, or metastatic disease). To validate our cohort, we confirmed expected correlations of all measured parameters of aggressiveness by correlating them with each other. In summary, vascular patterns in ductal carcinoma in situ do not correlate with the predictors of aggressive behavior, suggesting that the biologic potential of ductal carcinoma in situ is independent of angiogenesis.

  10. Squamous cell carcinoma in a capybara (Hydrochoerus hydrochaeris).

    PubMed

    Hamano, Takahisa; Terasawa, Fumio; Tachikawa, Yoshiharu; Murai, Atsuko; Mori, Takashi; El-Dakhly, Khaled; Sakai, Hiroki; Yanai, Tokuma

    2014-09-01

    A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara.

  11. Squamous Cell Carcinoma in a Capybara (Hydrochoerus hydrochaeris)

    PubMed Central

    HAMANO, Takahisa; TERASAWA, Fumio; TACHIKAWA, Yoshiharu; MURAI, Atsuko; MORI, Takashi; EL-DAKHLY, Khaled; SAKAI, Hiroki; YANAI, Tokuma

    2014-01-01

    ABSTRACT A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara. PMID:24909968

  12. Treatment for metastatic nasopharyngeal carcinoma.

    PubMed

    Bensouda, Y; Kaikani, W; Ahbeddou, N; Rahhali, R; Jabri, M; Mrabti, H; Boussen, H; Errihani, H

    2011-04-01

    Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC. PMID:21177151

  13. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan

    PubMed Central

    Kudo, Masatoshi; Matsui, Osamu; Izumi, Namiki; Iijima, Hiroko; Kadoya, Masumi; Imai, Yasuharu; Okusaka, Takuji; Miyayama, Shiro; Tsuchiya, Kaoru; Ueshima, Kazuomi; Hiraoka, Atsushi; Ikeda, Masafumi; Ogasawara, Sadahisa; Yamashita, Tatsuya; Minami, Tetsuya; Yamakado, Koichiro

    2014-01-01

    The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness. PMID:26280007

  14. Clinically-inspired automatic classification of ovarian carcinoma subtypes

    PubMed Central

    BenTaieb, Aïcha; Nosrati, Masoud S; Li-Chang, Hector; Huntsman, David; Hamarneh, Ghassan

    2016-01-01

    Context: It has been shown that ovarian carcinoma subtypes are distinct pathologic entities with differing prognostic and therapeutic implications. Histotyping by pathologists has good reproducibility, but occasional cases are challenging and require immunohistochemistry and subspecialty consultation. Motivated by the need for more accurate and reproducible diagnoses and to facilitate pathologists’ workflow, we propose an automatic framework for ovarian carcinoma classification. Materials and Methods: Our method is inspired by pathologists’ workflow. We analyse imaged tissues at two magnification levels and extract clinically-inspired color, texture, and segmentation-based shape descriptors using image-processing methods. We propose a carefully designed machine learning technique composed of four modules: A dissimilarity matrix, dimensionality reduction, feature selection and a support vector machine classifier to separate the five ovarian carcinoma subtypes using the extracted features. Results: This paper presents the details of our implementation and its validation on a clinically derived dataset of eighty high-resolution histopathology images. The proposed system achieved a multiclass classification accuracy of 95.0% when classifying unseen tissues. Assessment of the classifier's confusion (confusion matrix) between the five different ovarian carcinoma subtypes agrees with clinician's confusion and reflects the difficulty in diagnosing endometrioid and serous carcinomas. Conclusions: Our results from this first study highlight the difficulty of ovarian carcinoma diagnosis which originate from the intrinsic class-imbalance observed among subtypes and suggest that the automatic analysis of ovarian carcinoma subtypes could be valuable to clinician's diagnostic procedure by providing a second opinion. PMID:27563487

  15. Merkel cell carcinoma with glandular differentiation admixed with sweat gland carcinoma and spindle cell carcinoma: histogenesis of merkel cell carcinoma from hair follicle stem cells.

    PubMed

    Koba, Shinichi; Nagase, Kotaro; Ikeda, Satoshi; Aoki, Shigehisa; Misago, Noriyuki; Narisawa, Yutaka

    2015-03-01

    We describe a unique case of Merkel cell carcinoma (MCC) with a heterogeneous differentiation exhibiting distinct triphasic phenotypic differentiation features: small cells typical of MCC, sweat gland carcinoma (sweat gland Ca.) with possible decapitation secretion, and spindle cell carcinoma (spindle cell Ca.). The patient was an 84-year-old Japanese woman. We evaluated the present case immunohistochemically with various antibodies. The histological features showed a gradual transition from MCC to sweat gland Ca. and spindle cell Ca. For clarifying the histogenesis, immunophenotypic analysis of the 3 different components of the carcinoma was performed using hair follicle stem cell markers (eg, CK15, CK19, and CD200) that have been identified as biomarkers of human bulge cells. The triphasic components immunohistochemically shared the characteristic feature of CK19 and CD200 expression. We posit that the MCC arose from hair follicle stem cells residing within the bulge area where Merkel cells are preferentially situated. Based on our findings, we recommend adding this rare neoplasm to the expanding morphological spectrum of MCC.

  16. Integrated genomic characterization of endometrial carcinoma.

    PubMed

    Kandoth, Cyriac; Schultz, Nikolaus; Cherniack, Andrew D; Akbani, Rehan; Liu, Yuexin; Shen, Hui; Robertson, A Gordon; Pashtan, Itai; Shen, Ronglai; Benz, Christopher C; Yau, Christina; Laird, Peter W; Ding, Li; Zhang, Wei; Mills, Gordon B; Kucherlapati, Raju; Mardis, Elaine R; Levine, Douglas A

    2013-05-01

    We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

  17. [Thyroglossal cyst and papillary carcinoma. Management proposals].

    PubMed

    Palomino-Martínez, Brisa Denise; Beristain-Hernández, José Luis; Piscil-Salazar, Marco Antonio; Villalpando-Mendoza, César Javier; Velázquez-García, José Arturo

    2014-01-01

    The thyroid descends through the foramen cecum leaving the thyroglossal duct, which disappears between the fifth and the tenth week of pregnancy. The lack of involution of any part of this duct results in thyroglossal cyst formation. Its diagnostic approach is made by cervical ultrasound, computed tomography and magnetic resonance imaging. Approximately 1 % of the thyroglossal cyst formation contains malignant elements, and the most reported primary tumor has been papillary carcinoma. The recommended treatment for these carcinomas is controversial and it has evolved as time goes by. From Sistrunk procedure to neck dissection with total thyroidectomy and complementary therapies, such as iodine ablation and thyroid supplements, yet there is still no consensus as to the type of surgery and postoperative management it should be used to treat this carcinoma. Therapy should be applied according to each specific case, and it should be based on histological diagnosis, the invasive character of the tumor, and the lymph node affectation. In this paper we review the literature published so far with regards to the treatment of this carcinoma.

  18. Retinopathy secondary to radiation therapy for squamous cell carcinoma

    SciTech Connect

    Groomer, A.E.; Gutwein, D.E. )

    1989-09-01

    This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed.

  19. Collecting duct carcinoma of the renal medulla presenting with paraplegia.

    PubMed

    Ockrim, J; Tsiriopoulos, I; Rees, H; Mendoza, N; Christmas, T J

    2005-01-01

    We report an interesting case of a patient with collecting duct carcinoma arising from the left kidney who presented with paraplegia secondary to metastases. The diagnosis was based on CT and histology. To our knowledge this is the first case of collecting duct carcinoma to present with paraplegia. The literature review also highlights the rarity of this disease with less than a hundred cases reported to date and the aggressive nature and poor prognosis despite prompt interventions.

  20. [Merkel cell carcinoma (trabecular carcinoma) of the skin].

    PubMed

    Zala, L; Armagni, C; Krebs, A

    1983-04-01

    The Merkel cell carcinoma was first designated some years ago by the descriptive term trabecular carcinoma. Both names refer to a skin tumor occurring in elderly patients. This is another example where ultrastructural differentiating criteria are necessary for a definite diagnosis i.e., identification of so-called neurosecretory-like granules by electron microscopy. We report clinical, histological, ultrastructural, and histogenetic aspects of such a disease in a woman suffering from a metastasizing Merkel cell carcinoma. PMID:6853165

  1. Gene Set-Based Functionome Analysis of Pathogenesis in Epithelial Ovarian Serous Carcinoma and the Molecular Features in Different FIGO Stages

    PubMed Central

    Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Ming-Jie; Chang, Cheng-Chang; Yen, Ming-Shyen; Chiou, Shih-Hwa

    2016-01-01

    Serous carcinoma (SC) is the most common subtype of epithelial ovarian carcinoma and is divided into four stages by the Federation of Gynecologists and Obstetrics (FIGO) staging system. Currently, the molecular functions and biological processes of SC at different FIGO stages have not been quantified. Here, we conducted a whole-genome integrative analysis to investigate the functions of SC at different stages. The function, as defined by the GO term or canonical pathway gene set, was quantified by measuring the changes in the gene expressional order between cancerous and normal control states. The quantified function, i.e., the gene set regularity (GSR) index, was utilized to investigate the pathogenesis and functional regulation of SC at different FIGO stages. We showed that the informativeness of the GSR indices was sufficient for accurate pattern recognition and classification for machine learning. The function regularity presented by the GSR indices showed stepwise deterioration during SC progression from FIGO stage I to stage IV. The pathogenesis of SC was centered on cell cycle deregulation and accompanied with multiple functional aberrations as well as their interactions. PMID:27275818

  2. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma.

    PubMed

    Bavle, Radhika M; Govinda, Girish; Venkataramanaiah, Padmalatha Gundappanayakanahalli; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-07-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature. PMID:27630965

  3. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika M; Govinda, Girish; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-01-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature.

  4. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika M; Govinda, Girish; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-01-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature. PMID:27630965

  5. Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: Clinical experience and dose-volume histogram analysis

    SciTech Connect

    Weitmann, Hajo Dirk . E-mail: dirk.weitmann@akhwien.at; Poetter, Richard; Waldhaeusl, Claudia; Nechvile, Elisabeth; Kirisits, Christian; Knocke, Tomas Hendrik

    2005-06-01

    Purpose: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. Methods and Materials: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and {alpha}/{beta} of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. Results: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative

  6. Independent bilateral primary bronchial carcinomas

    PubMed Central

    Chaudhuri, M. Ray

    1971-01-01

    Independent bilateral primary bronchial carcinomas are not common. Since Beyreuther's description in 1924, 16 well-documented cases of independent primary bronchial carcinomas of different histology have been described. From 1965 to 1970, eight cases were seen at the London Chest Hospital. In order to make the diagnosis of a second primary bronchial carcinoma, each tumour should be malignant and neither should be a metastasis from the other. To meet this last criterion, the histopathological features of the two tumours must be different. Many cases have been described in the literature as double primary bronchial carcinomas where the second primary had the same histological features as the first. Images PMID:4327711

  7. Primary biliary carcinoma: CT evaluation

    SciTech Connect

    Thorsen, M.K.; Quiroz, F.; Lawson, T.L.; Smith, D.F.; Foley, W.D.; Steward, E.T.

    1984-08-01

    Fifty-three patients with documented primary biliary carcinoma were studied with computed tomography. Twenty-six patients had gallbladder carcinoma and 27 patients had carcinoma of the biliary ductal system. Ninety percent of patients with gallbladder cancer had an intraluminal mass. Local invasion into the liver was common. The majority of patients with biliary ductal carcinoma had dilated bile ducts, while only 50% of patients with gallbladder cancer had biliary ductal dilatation. The most common location of tumor involving the extrahepatic biliary ductal system was the distal common bile duct. This occurred in eight patients out of 27, or 30% of the cases.

  8. Merkel cell carcinoma

    PubMed Central

    Koljonen, Virve

    2006-01-01

    Background Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region. Methods MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options. Results The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective. Conclusion Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care. PMID:16466578

  9. Primary duodenal carcinoma.

    PubMed Central

    Adedeji, O. A.; Trescoli-Serrano, C.; Garcia-Zarco, M.

    1995-01-01

    Eight cases of primary duodenal carcinoma in a district general hospital are presented. The cases highlight the advanced state of the disease at presentation, the difficulty in diagnosis, and its poor prognosis. Duodenal carcinoma occurs in both sexes worldwide with no predisposing factors in the majority of cases. There is an increased risk in patients with familial adenomatous polyposis and adenomas of the duodenum. Duodenal carcinoma occurs about 22 years from the diagnosis of familial adenomatous polyposis in about 2% of patients, forming over 50% of upper gastrointestinal cancers occurring in these patients. Carcinomatous changes occur in 30 to 60% of duodenal villous adenomas and much less in tubulo-villous and tubular adenomas. These categories of patients should be screened and adequately followed up. Aggressive and radical surgery, even in the presence of locally advanced disease and lymph node involvement, gives a better outcome. When curative surgery is not possible, chemotherapy must accompany palliation with or without radiotherapy. Pre-operative chemotherapy may facilitate a curative radical resection. The general five-year survival is 17-33% but some centres have achieved a five-year survival of 40-60% with aggressive management of these patients. PMID:7644397

  10. Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma.

    PubMed

    Li, Qiang; Bagrodia, Aditya; Cha, Eugene K; Coleman, Jonathan A

    2016-02-01

    Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare, and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers. PMID:26757906

  11. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

    2015-03-01

    The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

  12. Multi-Target Approach to Metastatic Adrenal Cell Carcinoma.

    PubMed

    Wahab, Norasyikin A; Zainudin, Suehazlyn; AbAziz, Aini; Mustafa, Norlaila; Sukor, Norlela; Kamaruddin, Nor Azmi

    2016-09-01

    Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months. PMID:27631184

  13. A systems biology-based investigation into the therapeutic effects of Gansui Banxia Tang on reversing the imbalanced network of hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Zhang, Yanqiong; Guo, Xiaodong; Wang, Danhua; Li, Ruisheng; Li, Xiaojuan; Xu, Ying; Liu, Zhenli; Song, Zhiqian; Lin, Ya; Li, Zhiyan; Lin, Na

    2014-02-01

    Several complex molecular events are involved in tumorigenesis of hepatocellular carcinoma (HCC). The interactions of these molecules may constitute the HCC imbalanced network. Gansui Banxia Tang (GSBXT), as a classic Chinese herbal formula, is a popular complementary and alternative medicine modality for treating HCC. In order to investigate the therapeutic effects and the pharmacological mechanisms of GSBXT on reversing HCC imbalanced network, we in the current study developed a comprehensive systems approach of integrating disease-specific and drug-specific networks, and successfully revealed the relationships of the ingredients in GSBXT with their putative targets, and with HCC significant molecules and HCC related pathway systems for the first time. Meanwhile, further experimental validation also demonstrated the preventive effects of GSBXT on tumor growth in mice and its regulatory effects on potential targets.

  14. [Urothelial carcinoma in a pyelocaliceal cyst].

    PubMed

    Abate, Danilo; Vella, Marco; Alonge, Vincenza; Serretta, Vincenzo

    2014-01-01

    Renal complex cysts are lesions whose nature can be either benign or malignant. Depending on the presence of septa, solid components, enhancement or calcifications, they are distinguished according to the Bosniak classification based on CT findings, as well as MRI and ETG. We report a rare case of urothelial carcinoma, originating over a pyelocalyceal cyst in a 50-year-old man, and classified as Bosniak IIF by CT and MRI investigations.

  15. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    SciTech Connect

    Bag, Swarnendu; Banerjee, Deb Ranjan; Basak, Amit; Das, Amit Kumar; Pal, Mousumi; Banerjee, Rita; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

    2015-04-17

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

  16. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  17. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    PubMed

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary.

  18. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    PubMed

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. PMID:27461832

  19. Development of a new outcome prediction model for Chinese patients with penile squamous cell carcinoma based on preoperative serum C-reactive protein, body mass index, and standard pathological risk factors: the TNCB score group system

    PubMed Central

    Li, Jing; Mi, Qi-Wu; Chen, Xiao-Feng; Zhao, Qi; Li, Yong-Hong; Chen, Jie-Ping; Deng, Chuang-Zhong; Ye, Yun-Lin; Zhong, Ming-Zhu; Liu, Zhuo-Wei; Qin, Zi-Ke; Lin, Xiang-Tian; Liang, Wei-Cong; Han, Hui; Zhou, Fang-Jian

    2016-01-01

    Purpose To determine the predictive value and feasibility of the new outcome prediction model for Chinese patients with penile squamous cell carcinoma. Results The 3-year disease-specific survival (DSS) was 92.3% in patients with < 8.70 mg/L CRP and 54.9% in those with elevated CRP (P < 0.001). The 3-year DSS was 86.5% in patients with a BMI < 22.6 Kg/m2 and 69.9% in those with a higher BMI (P = 0.025). In a multivariate analysis, pathological T stage (P < 0.001), pathological N stage (P = 0.002), BMI (P = 0.002), and CRP (P = 0.004) were independent predictors of DSS. A new scoring model was developed, consisting of BMI, CRP, and tumor T and N classification. In our study, we found that the addition of the above-mentioned parameters significantly increased the predictive accuracy of the system of the American Joint Committee on Cancer (AJCC) anatomic stage group. The accuracy of the new prediction category was verified. Methods A total of 172 Chinese patients with penile squamous cell cancer were analyzed retrospectively between November 2005 and November 2014. Statistical data analysis was conducted using the nonparametric method. Survival analysis was performed with the log-rank test and the Cox proportional hazard model. Based on regression estimates of significant parameters in multivariate analysis, a new BMI-, CRP- and pathologic factors-based scoring model was developed to predict disease-specific outcomes. The predictive accuracy of the model was evaluated using the internal and external validation. Conclusion The present study demonstrated that the TNCB score group system maybe a precise and easy to use tool for predicting outcomes in Chinese penile squamous cell carcinoma patients. PMID:26980738

  20. Incidence of Ovarian, Peritoneal, and Fallopian Tube Carcinomas in the United States, 1995–2004

    PubMed Central

    Goodman, Marc T.; Shvetsov, Yurii B.

    2009-01-01

    Objective The objective of this analysis was to describe the distribution of pelvic carcinomas in the United States by demographic, pathologic, and clinical features. Methods Carcinomas of the ovary (N=112,541), peritoneum (N=6,458), and fallopian tube (N=3,479) were identified through 24 population-based registries in the United States during the period 1995–2004. Age-adjusted incidence rates (AAIR) were calculated per million population using counts derived from the 2000 US census. Results The AAIR for ovarian carcinoma (119.9 per million) was substantially higher than for peritoneal (6.78 per million) or fallopian tube (3.72 per million) carcinomas. White women had the highest rates for all three malignancies. Rates for peritoneal carcinoma were lowest among Black women (2.88 per million) and rates for fallopian tube carcinoma were lowest among Hispanic women (2.45 per million). Serous carcinomas were the most commonly diagnosed histologic type for all anatomic sites. Peritoneal carcinomas were diagnosed at later ages (mean 67 years) and more advanced stages (85% regional/distant) compared to fallopian tube carcinomas (mean 64 years; 62% regional/distant) and ovarian carcinomas (mean 63 years; 76% regional/distant). Incidence for all three pelvic carcinomas was lowest in the South. Time trend analyses between 1973 and 2005 exhibited a significant decline in ovarian carcinoma incidence, and rises in the rates of peritoneal and fallopian tube cancers. Conclusions Similarities in the incidence patterns for ovarian, peritoneal, and fallopian tube carcinomas support the likelihood of a common molecular pathogenesis. PMID:19124490

  1. Lobomycosis and squamous cell carcinoma*

    PubMed Central

    Nogueira, Lisiane; Rodrigues, Luciana; Rodrigues, Carlos Alberto Chirano; Santos, Mônica; Talhari, Sinésio; Talhari, Carolina

    2013-01-01

    The occurence of squamous cell carcinoma on long-lasting ulcers is classic. Malignant transformation may occur on burn scars and chronic ulcers of varying etiology, including infectious agents. Transformation of old lobomycosis lesion scars into squamous cell carcinoma has been rarely reported. Careful and long-term follow-up of such patients is important to avoid carcinomatous transformation. PMID:23739701

  2. Upper urinary tract urothelial carcinoma with intratubular spread

    PubMed Central

    Sarungbam, Judy; Kurtis, Boaz; Phillips, John; Cai, Dongming; Zhang, David; Humayun, Islam; Yang, Ximing; Zhong, Minghao

    2014-01-01

    Upper urinary tract urothelial cell carcinomas (UUT-UCs) are uncommon and are defined as urothelial carcinoma involving the urinary tract from the renal calyces, renal pelvis to the distal ureter. One well-known an peculiar histopathological finding in UUT-UC is urothelial carcinoma with intratubular spread (retrograde spread within renal tubules). However, this special feature has not been systematically studied. We therefore collected a total of 53 consecutive cases of upper urinary tract urothelial carcinomas (UUT-UCs), and studied the clinical and pathological features of intratubular spread (IS). A cocktail stain comprised of antibodies PAX8 and p63 together with PAS was validated and employed to facilitate the study of intratubular spread. Seventeen cases (31.5%) showed intratubular spread demonstrated by either H&E stain and/or the cocktail stain. All of the 17 cases wit intratubular spread had tumor involvement of the renal calyx; the majority of these (14/17, 82.4%) were high grade urothelial carcinoma and the remainder (3/17, 17.6%) were low grade. 4 of 17cases (23.5%) were non-invasive. We classified intratubular spread into 4 different types, based on histopathological patterns: pagetoid, typical, florid, and secondary invasion from intratubular spread. In conclusion, study shows intratubular spread of urothelial carcinoma is fairly common phenomenon in UUT-UC and is associated with a variety of clinical-pathological features. High grade UUT-UC tends to have more extensive intratubular spread and secondary invasion into renal parenchyma. Distinct morphological characteristics as well as the staining pattern from a unique cocktail stain help to identify and evaluate intratubular spread of urothelial carcinoma. Recognizing these different types of intratubular spreading (IS) is crucial for accurate staging of some upper urinary tract urothelial carcinomas (UUT-UCs). PMID:25374911

  3. Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

    PubMed Central

    Nagai, Takashi; Naiki, Taku; Kawai, Noriyasu; Iida, Keitaro; Etani, Toshiki; Ando, Ryosuke; Hamamoto, Shuzo; Sugiyama, Yosuke; Okada, Atsushi; Mizuno, Kentaro; Umemoto, Yukihiro; Yasui, Takahiro

    2016-01-01

    Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC) values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB. PMID:27099604

  4. Basal cell carcinoma

    PubMed Central

    2010-01-01

    Introduction Basal cell carcinoma (BCC) is the most common form of skin cancer, predominantly affecting the head and neck, and can be diagnosed clinically in most cases. Metastasis of BCC is rare, but localised tissue invasion and destruction can lead to morbidity. Incidence of BCC increases markedly after the age of 40 years, but incidence in younger people is rising, possibly as a result of increased sun exposure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions on treatment response/recurrence (within 1 year of therapy) in people with basal cell carcinoma? What are the effects of interventions on long-term recurrence (a minimum of 2 years after treatment) in people with basal cell carcinoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: cryotherapy/cryosurgery, curettage and cautery/electrodesiccation, fluorouracil, imiquimod 5% cream, photodynamic therapy, and surgery (conventional or Mohs' micrographic surgery). PMID:21718567

  5. Primary hyperparathyroidism due to parathyroid carcinoma.

    PubMed

    Mendoza, V; Hernández, A F; Márquez, M L; Delgadillo, M A; Peña, J; Mercado, M

    1997-01-01

    Most cases of primary hyperparathyroidism are due to either a parathyroid adenoma or to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established based on pathological criteria of vascular and capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We report the case of a middle-aged woman with a long standing history of nephrolithiasis, who presented with a palpable neck mass, weight loss, severe hypercalcemia and hypophosphatemia, as well as very high serum levels of intact parathyroid hormone. Surgical neck exploration revealed a large tumor that invaded trachea, esophagus, reccurrent laryngeal nerve, right apical pleura and right carotid artery. Pathological examination confirmed the invasive nature of the tumor. Along with the case report, we review the literature and discuss the diagnostic and therapeutic options of this rare condition.

  6. Computed tomographic appearance of resectable pancreatic carcinoma

    SciTech Connect

    Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

    1982-06-01

    Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT.

  7. RET rearrangements in familial papillary thyroid carcinomas.

    PubMed

    Corvi, R; Lesueur, F; Martinez-Alfaro, M; Zini, M; Decaussin, M; Murat, A; Romeo, G

    2001-09-20

    Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized by a more aggressive phenotype than that of its sporadic counterpart. Its mode of inheritance as well as its genetic and molecular bases are still poorly understood. On the contrary, genetic alterations in sporadic papillary thyroid carcinoma (PTC) are better characterized, the most common one involving the activation of the proto-oncogene RET through somatic rearrangements. In the present study, we investigated by interphase fluorescence in situ hybridization the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC and the adenoma from the same patient carry a RET rearrangement (type PTC1) and that this rearrangement is absent in the germline. Furthermore, we excluded a RET haplotype sharing in two brothers of the same family. These results show that RET rearrangements can indeed be found in FPTC and confirm that RET is not involved in the inherited predisposition to FPTC.

  8. BM-12CEREBRAL INFARCTION SECONDARY TO PULMONARY VEIN COMPRESSION AND LEFT ATRIAL APPENDAGE TUMOR INFILTRATION AS THE PRESENTING SIGN OF METASTATIC SQUAMOUS CELL CARCINOMA OF THE BASE OF THE TONGUE

    PubMed Central

    Dredla, Brynn; Siegel, Jason; Jaeckle, Kurt

    2014-01-01

    BACKGROUND: Squamous cell carcinoma of the tongue has been documented to metastasize to the lungs and rarely involve the heart. The majority of documented cases of cardiac metastases are from postmortem analysis. Cases of sudden death, syncope, and dyspnea have been reported. However, stroke and tumor embolization to the brain as the initial clinical presentation has not been documented in the English literature. METHODS: Case Report. RESULTS: This case addresses a 61-year-old male with Stage IVA squamous cell carcinoma of the left tongue base, believed to be in remission after systemic chemotherapy and local radiation, who presented with acute cerebral infarctions involving multiple vascular territories. Cardiac CT obtained during stroke etiology evaluation displayed metastatic disease compressing the pulmonary vein resulting in virtual pulmonary vein thrombus. Transthoracic echocardiogram was negative for cardiac valvular pathology. Anticoagulation was initiated. Twelve days later he returned with recurrent strokes and suspected tumor embolization to the brain. Imaging displayed left atrial appendage structural abnormality highly suggestive of tumor infiltration. CONCLUSION: Cardiac metastases are rare and non-myxomatous tumor embolization to the brain even rarer especially in the setting of cerebral infarction due to pulmonary vein thrombus. Here we describe a case of multiple acute cerebral infarctions appearing from a proximal source refractory to anticoagulation. Thromboembolism from the pulmonary vein and tumor embolization from cardiac metastases are the likely mechanisms for his clinical presentation and radiographic findings. This case demonstrates the complexity of multiple stroke etiologies in one patient and the importance of cardiac imaging in stroke evaluation, particularly in the setting of a patient with a history of cancer.

  9. Perianal Basal Cell Carcinoma

    PubMed Central

    Bulur, Isil; Boyuk, Emine; Saracoglu, Zeynep Nurhan; Arik, Deniz

    2015-01-01

    Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Exposure to ultraviolet light is an important risk factor for BCC development and the disorder therefore develops commonly on body areas that are more exposed to sunlight, such as the face and neck. It is uncommon in the closed area of the body and quite rare in the perianal and genital regions. Herein, we report a 34-year-old patient with perianal BCC who had no additional risk factors. PMID:25848349

  10. Carcinoma Adenomatodes Cervicis Uteri

    PubMed Central

    Spencer, Herbert R.

    1926-01-01

    The case is one of carcinoma adenomatodes (adenoma malignum) cervicis uteri, which occurred in a patient, aged 49. Vaginal hysterectomy was performed with the Pacquelin cautery, and the patient remains well after 22 years. Attention is drawn to the rarity of the disease, and the point is emphasized that in true cases of the disease the glandular epithelium is nowhere proliferated, and therefore reliance on microscopic examination alone for the diagnosis may lead to serious error. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:19985105

  11. Comparison of Four Cisplatin-Based Radiochemotherapy Regimens for Nonmetastatic Stage III/IV Squamous Cell Carcinoma of the Head and Neck;Head-and-neck cancer; Cisplatin-based radiochemotherapy; Toxicity; Treatment outcomes

    SciTech Connect

    Rades, Dirk; Kronemann, Stefanie; Meyners, Thekla; Bohlen, Guenther; Tribius, Silke; Kazic, Nadja; Schroeder, Ursula; Hakim, Samer G.; Schild, Steven E.; Dunst, Juergen

    2011-07-15

    Purpose: To compare the outcomes of four cisplatin-based radiochemotherapy regimens in 311 patients with Stage III/IV squamous cell carcinoma of the head and neck. Methods and Materials: Concurrent chemotherapy consisted of three courses of cisplatin 100 mg/m{sup 2} on Day 1 (Group A, n = 74), two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 plus 5-fluorouracil 1,000 mg/m{sup 2} on Days 1-5 (Group B, n = 49), two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 plus 5-fluorouracil 600 mg/m{sup 2} on Days 1-5 (Group C, n = 102), or two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 (Group D, n = 86). The groups were retrospectively compared for toxicity and outcomes, and 11 additional factors were evaluated for outcomes. Results: No significant difference was observed among the groups regarding radiation-related acute oral mucositis and radiation-related late toxicities. Acute Grade 3 skin toxicity was significantly more frequent in Group B than in the patients of the other three groups (p = .013). The chemotherapy-related Grade 3 nausea/vomiting rate was 24% for Group A, 8% for Group B, 9% for Group C, and 6% for Group D (p = .003). The corresponding Grade 3 nephrotoxicity rates were 8%, 1%, 2%, and 1% (p = .019). The corresponding Grade 3-4 hematologic toxicity rates were 35%, 41%, 19%, and 21% (p = .027). Chemotherapy could be completed in 50%, 59%, 74%, and 83% of the Group A, B, C, and D patients, respectively (p = .002). Toxicity-related radiotherapy breaks occurred in 39%, 43%, 21%, and 15% of Groups A, B, C, and D, respectively (p = .005). The 3-year locoregional control rate was 67%, 72%, 60%, and 59% for Groups A, B, C, and D, respectively (p = .48). The corresponding 3-year metastasis-free survival rates were 67%, 74%, 63%, and 79% (p = .31), and the corresponding 3-year survival rates were 60%, 63%, 50%, and 71% (p = .056). On multivariate analysis, Karnofsky performance status, histologic grade, T/N category, preradiotherapy hemoglobin level

  12. Accuracy of classifying poorly differentiated non-small cell lung carcinoma biopsies with commonly used lung carcinoma markers.

    PubMed

    Zachara-Szczakowski, Susanna; Verdun, Tyler; Churg, Andrew

    2015-05-01

    Immunohistochemical (IHC) staining is an important adjunct to the classification of non-small cell lung carcinoma (NSCLC). Several studies have used tissue microarrays derived from resection specimens to evaluate the accuracy of IHC staining for classifying NSCLC, but few have used actual biopsies of poorly differentiated carcinomas, and the question of how often biopsy IHC in such tumors leads to the correct classification has received little attention. We identified 40 cases of NSCLC that, on biopsy, could not be subclassified by morphology and that had subsequent resection specimens. TTF-1, napsin, p63/p40, and CK5 or a subset thereof were used for IHC classification. Of the 40 cases classified by IHC on biopsy, 33 (82%) had no change in diagnosis after resection. Of the remaining 7 cases, 3 were classified as NSCLC--not otherwise specified on biopsy and subclassified as either adenocarcinoma or squamous cell carcinoma (SCC) on the surgical specimen. One adenocarcinoma biopsy was reclassified as pleomorphic carcinoma. Two SCCs were changed to adenosquamous carcinoma, and 1 SCC was changed to large cell lung carcinoma. Only 1 antibody pair (2%) was discordant between biopsy, and almost all reclassifications were done based on morphologic features rather than change in IHC pattern. We conclude that IHC staining allows accurate subclassification of poorly differentiated NSCLCs on small lung biopsies in most cases, but there is still a substantial "miss" rate (here, 18%). Surgical resection specimens allow further subclassification, mainly due to architectural features not present in the biopsies.

  13. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma

    PubMed Central

    Kong, Cheng; Zhu, Xiang-zhi; Lee, Tsair-Fwu; Feng, Ping-bo; Xu, Jian-hua; Qian, Pu-dong; Zhang, Lan-fang; He, Xia; Huang, Sheng-fu; Zhang, Yi-qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  14. Effects of curcumin on global gene expression profiles in the highly invasive human breast carcinoma cell line MDA-MB 231: A gene network-based microarray analysis.

    PubMed

    Cine, Naci; Limtrakul, Pornngarm; Sunnetci, Deniz; Nagy, Balint; Savli, Hakan

    2013-01-01

    Curcumin, or diferuloylmethane, is a major chemical component of turmeric (Curcuma longa Linn.) that has been consumed as a dietary spice through the ages. This yellow-colored polyphenol has a notably wide range of beneficial properties, including anti-inflammatory, antioxidant, antitumoral, anti-invasive and anti-metastatic activity. In the present study, microarray gene expression analysis was applied to identify the curcumin-regulated genes in a highly invasive human breast carcinoma cell line (MDA-MB 231). Cells were cultured with curcumin (20 μM) for 24 h; total RNA was isolated and hybridized to Whole Human Genome Microarray slides. Gene set enrichment analyses on our whole genome expression data revealed downregulation of the EGF pathway elements following curcumin treatment. Furthermore, gene network analysis identified a significantly relevant network among the differentially expressed genes, centered on the EGR1 and FOS genes. The members of these pathways and networks play an essential role in the regulation of cancer cell growth and development; the majority exhibited decreased expression levels following treatment with curcumin. These observations suggest that curcumin is an excellent candidate for the prevention and treatment of breast cancer. PMID:23251236

  15. Integrative transcriptomics-based identification of cryptic drivers of taxol-resistance genes in ovarian carcinoma cells: Analysis of the androgen receptor.

    PubMed

    Sun, Nian-Kang; Huang, Shang-Lang; Lu, Hsing-Pang; Chang, Ting-Chang; Chao, Chuck C-K

    2015-09-29

    A systematic analysis of the genes involved in taxol resistance (txr) has never been performed. In the present study, we created txr ovarian carcinoma cell lines to identify the genes involved in chemoresistance. Transcriptome analysis revealed 1,194 overexpressed genes in txr cells. Among the upregulated genes, more than 12 cryptic transcription factors were identified using MetaCore analysis (including AR, C/EBPβ, ERα, HNF4α, c-Jun/AP-1, c-Myc, and SP-1). Notably, individual silencing of these transcription factors (except HNF4`)sensitized txr cells to taxol. The androgen receptor (AR) and its target genes were selected for further analysis. Silencing AR using RNA interference produced a 3-fold sensitization to taxol in txr cells, a response similar to that produced by silencing abcb1. AR silencing also downregulated the expression of prominent txr gene candidates (including abcb1, abcb6, abcg2, bmp5, fat3, fgfr2, h1f0, srcrb4d, and tmprss15). In contrast, AR activation using the agonist DHT upregulated expression of the target genes. Individually silencing seven out of nine (78%) AR-regulated txr genes sensitized txr cells to taxol. Inhibition of AKT and JNK cellular kinases using chemical inhibitors caused a dramatic suppression of AR expression. These results indicate that the AR represents a critical driver of gene expression involved in txr.

  16. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

  17. Proteome Differences between Hepatitis B Virus Genotype-B- and Genotype-C-Induced Hepatocellular Carcinoma Revealed by iTRAQ-Based Quantitative Proteomics.

    PubMed

    Wei, Dahai; Zeng, Yongyi; Xing, Xiaohua; Liu, Hongzhi; Lin, Minjie; Han, Xiao; Liu, Xiaolong; Liu, Jingfeng

    2016-02-01

    Hepatitis B virus (HBV) is the main cause of hepatocellular carcinoma (HCC) in southeast Asia where HBV genotype B and genotype C are the most prevalent. Viral genotypes have been reported to significantly affect the clinical outcomes of HCC. However, the underlying molecular differences among different genotypes of HBV virus infected HCC have not been revealed. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify the proteome differences between the HBV genotypes B- and C-induced HCC. In brief, a total of 83 proteins in the surrounding noncancerous tissues and 136 proteins in the cancerous tissues between HBV genotype-B- and genotype-C-induced HCC were identified, respectively. This information revealed that there might be different molecular mechanisms of the tumorigenesis and development of HBV genotypes B- and C-induced HCC. Furthermore, our results indicate that the two proteins ARFIP2 and ANXA1 might be potential biomarkers for distinguishing the HBV genotypes B- and C-induced HCC. Thus, the quantitative proteomic analysis revealed molecular differences between the HBV genotypes B- and C-induced HCC, and might provide fundamental information for further deep study. PMID:26709725

  18. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

    PubMed

    Kong, Cheng; Zhu, Xiang-Zhi; Lee, Tsair-Fwu; Feng, Ping-Bo; Xu, Jian-Hua; Qian, Pu-Dong; Zhang, Lan-Fang; He, Xia; Huang, Sheng-Fu; Zhang, Yi-Qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  19. Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC.

    PubMed

    de Guadalupe Chávez-López, María; Pérez-Carreón, Julio Isael; Zuñiga-García, Violeta; Díaz-Chávez, José; Herrera, Luis A; Caro-Sánchez, Claudia Haydee; Acuña-Macías, Isabel; Gariglio, Patricio; Hernández-Gallegos, Elizabeth; Chiliquinga, Andrea Jazmín; Camacho, Javier

    2015-08-01

    Hepatocellular carcinoma (HCC) has very poor prognosis. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including the Eag1 (ether à-go-go-1) potassium channel that is overexpressed in human HCC. Eag1 channels are regulated by cancer etiological factors and have been proposed as early tumor markers. Here, we found that HepG2 and HuH-7 HCC cells displayed Eag1 messenger RNA (mRNA) and protein expression, determined by real-time RT-PCR and immunochemistry, respectively. Astemizole inhibited human HCC cell proliferation (assessed by metabolic activity assay) and induced apoptosis (studied with flow cytometry) in both cell lines. The subcellular Eag1 protein localization was modified by astemizole in the HepG2 cells. The treatment with astemizole prevented diethylnitrosamine (DEN)-induced rat HCC development in vivo (followed by studying γ-glutamyl transpeptidase (GGT) activity). The Eag1 mRNA and protein levels were increased in most DEN-treated groups but decreased after astemizole treatment. GGT activity was decreased by astemizole. The Eag1 protein was detected in cirrhotic and dysplastic rat livers. Astemizole might have clinical utility for HCC prevention and treatment, and Eag1 channels may be potential early HCC biomarkers. These data provide significant basis to include astemizole in HCC clinical trials. PMID:25783527

  20. Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.

    PubMed

    Zhang, Mengzi; Zhou, Xiaoju; Wang, Bo; Yung, Bryant C; Lee, Ly J; Ghoshal, Kalpana; Lee, Robert J

    2013-06-28

    Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73 nm, zeta potential of +3.5mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5 mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2-fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy.

  1. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris)

    PubMed Central

    Couture, Émilie L.; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-01-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors’ knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species. PMID:26663924

  2. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    PubMed

    Couture, Émilie L; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-12-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors' knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species. PMID:26663924

  3. Clear cell odontogenic carcinoma.

    PubMed

    Iezzi, G; Rubini, C; Fioroni, M; Piattelli, A

    2002-02-01

    Clear cell tumours, in the head and neck region, are usually derived from salivary or odontogenic tissues, or may be metastatic. A few clear cells may be present in odontogenic cysts, while, odontogenic neoplasms composed predominantly of clear cells are quite rare. They include calcifying epithelial odontogenic tumours (CEOT), ameloblastoma and odontogenic carcinoma. Clear cell odontogenic tumour (CCOT) has been classified in the last WHO classification as a benign tumour, but it is now recognized as a more sinister lesion and current opinion is that CCOT should be designated as a carcinoma. These tumours are characterized by aggressive growth, recurrences, and metastatic disease. A recent review of the literature has yielded 30 cases of tumours with similar characteristics. These tumours have a peak incidence in the 5th-7th decades, with a female predilection. The anterior portions of the jaws, especially the mandible, are most frequently affected. The aggressive potential of these neoplasms is well documented by the extensive invasion of adjacent tissues, multiple recurrences and regional or distant metastases.

  4. Etiopathogenesis of Differentiated Thyroid Carcinomas

    PubMed Central

    Makazlieva, Tanja; Vaskova, Olivija; Majstorov, Venjamin

    2016-01-01

    INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies. PMID:27703585

  5. Mutation analysis of hBUB1, human mitotic checkpoint gene in multiple carcinomas.

    PubMed

    Mimori, K; Inoue, H; Alder, H; Ueo, H; Tanaka, Y; Mori, M

    2001-01-01

    hBUB1 is a human homolog of yeast mitotic check point gene that plays an important role in chromosome segregation. Recently mutations of hBUB1 were reported in colorectal cancer cell lines, indicating that inactivation of this gene could be directly involved in aneuploidy in human carcinoma cells. To obtain information of the magnitude of hBUB1 inactivation in multiple carcinomas, we examined mutations in 59 multiple carcinoma cell lines showing single base alteration, however, there was no mutation of hBUB1 with amino acid change in these carcinomas. There were four silent mutations at codon 93, codon 735, codon 430 and codon 98 in KYSE190, TE8 esophageal carcinoma cells, KATOIII gastric carcinoma cells and 697 B cell leukemia cells, respectively. Two candidates of mutation were identified in TE3 esophageal carcinoma cells and 697 B cell leukemia cell line at codon 9 and codon 285, respectively. This result suggests that the inactivation of hBUB1 may be very rare in human carcinomas, or restricted to certain cell lines of colorectal carcinomas. PMID:11115566

  6. Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

    PubMed

    Solakoglu Kahraman, Dudu; Diniz, Gulden; Sayhan, Sevil; Ayaz, Duygu; Uncel, Melek; Karadeniz, Tugba; Akman, Tulay; Ozdemir, Aykut

    2015-10-01

    AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

  7. [Tumor markers of urinary tract carcinoma].

    PubMed

    Kikuchi, Haruhito

    2004-04-01

    The tumor markers for malignant tumors arisen from urinary system including prostate cancer were reviewed. As for renal cell carcinoma there was no good marker used in routine test level at present. In the diagnosis of urothelial (transitional cell) carcinoma, mainly bladder cancer, 3 methods (urinary BTA, NMP22 and BFP) are used now in Japan. They all seem to be not fully sufficient in respect of the specificity. In foreign countries, new tests such as urinary telomerase and BLCA-4 are used and have been evaluated. On the diagnosis of prostate cancer, serum total PSA is well established and used. Various PSA relation markers have been advocated for the differentiation between benign prostate hypertrophy and carcinoma in so called "gray zone" level of total PSA. In methods based on the molecular forms of PSA, the ratio of free PSA to total PSA (f/T) is widely use, and proPSA is a test that is expected. Other approaches such as volume of index PSA, age specific PSA reference range and PSA velocity are also in practical application. Human glandular kallikrein 2, which belong to the human kallikrein family as well as PSA, is expected as a tumor specific marker.

  8. [DNA methylation in thyroid carcinoma].

    PubMed

    Song, Xianyun; Shang, Xiaoling; Zhang, Yutuo

    2015-03-01

    Cancer has become clear that not merely gene variations but also epigenetic modifications may contribute to it. Epigenetic changes refer to stable alterations in gene expression with unrelated to changes in the underlying genetic sequence,resulting in heritable. DNA methylation is one of the common epigenetic changes. It control the gene expression through changing DNA conformation and stability, chromatin structer, DNA-protein interaction. The reversal of dysregulated DNA methylation has emerged as a potential strategy for the treatment of thyroid carcinoma. The artical will provide an overview of how DNA methylation contribute to thyroid carcinoma dissemination,invasion and metastasis and we will summarize the latest epigenetic therapies for thyroid carcinoma.

  9. Correlative imaging in gallbladder carcinoma.

    PubMed

    Willekens, I; Goethals, L R; Brussaard, C; Verdries, D; de Mey, J

    2014-01-01

    Gallbladder carcinoma is a relatively rare malignant epithelial neoplasm, arising from gallbladder mucosa. It is the fifth most common gastrointestinal malignancy and the most common biliary tract cancer. Early diagnosis remains difficult, because clinical symptoms are sparse and non-specific, often resulting in advanced stage disease at the time of diagnosis. The most common feature of gallbladder carcinoma on different imaging modalities is focal wall thickening, associated with a large eccentric tumor mass. In this case we report the imaging characteristics of gallbladder carcinoma on ultrasound, MDCT and 18F-FDG PET/CT.

  10. Myoepithelial carcinoma with contralateral invasive micropapillary carcinoma of the breast.

    PubMed

    Kwon, Sun Young; Bae, Young Kyung; Cho, Jihyong; Kang, Sun Hee

    2011-09-01

    Adenomyoepithelioma (AME) is a rare benign tumor composed of myoepithelial cells (MECs) which are located beneath the epithelial cells of exocrine glands, especially in breast and salivary glands. These tumor cells show biphasic proliferation of epithelial and MECs. Malignant AME is characterized by distant metastasis, local recurrence, cytologic atypia, high mitotic activity and infiltrating tumor margins. A 51-year-old woman presented with an 8 months growth in the left breast. She underwent core-needle biopsy and consecutively mammotome assisted biopsy at a local clinic. After resection, she complained about re-growing remnant lesion and a newly developed solid mass in the right breast. Finally, the remnant mass in the left breast was diagnosed with myoepithelial carcinoma. Concurrently, contralateral breast mass was diagnosed with invasive micropapillary carcinoma. Herein we report an unusual case of synchronous myoepithelial carcinoma and invasive micropapillary carcinoma of the breast with a review of literatures.

  11. Renal cell carcinoma with intramyocardial metastases

    PubMed Central

    2014-01-01

    Background Cardiac metastases from renal cell carcinoma without vena caval involvement are extremely rare with a limited number of cases reported in the worldwide literature until now. Nevertheless, this rare location of metastasis may significantly influence patient treatment and prognosis. Cooperation between oncology, cardiology, and urology teams are indispensable in cases of patients suffering from intramyocardial tumors. For these individuals, treatment guidelines based on large-scale studies are unavailable and only case/case series analysis may provide clinicians with decision assistance. Case presentation In this paper, we report a case of a 50-year-old Caucasian male diagnosed with a 10.2 × 10.3 × 10.0 cm lower pole left renal mass in January 2002. He was subsequently treated with immunochemotherapy, tyrosine kinase inhibitors (TKIs), and mTOR inhibitors (mTORIs) - that is sunitinib, everolimus, and sorafenib. In March 2012, contrast-enhancing tumors in the left myocardium (∅22 mm) and in the interventricular septum (∅26 mm) were seen on CT. Cardiology testing was conducted and the patient was treated with pazopanib with a profound response. Overall survival since the clear cell renal cell carcinoma (ccRCC) diagnosis was 11 years 2 months and since diagnosis of multiple heart metastases was 1 year. Conclusions Cardiac metastases present a unique disease course in renal cell carcinoma. Cardiac metastases may remain asymptomatic, as in the case of this patient at the time of diagnosis. The most common cardiac presentation of renal cell carcinoma is hypertension, but other cardiac presentations include shortness of breath, cough, and arrhythmias. Targeted systemic therapy with tyrosine kinase inhibitors may be useful for this group of patients, but necrosis in the myocardium can result in tamponade and death. Regular cardiac magnetic resonance imaging scans are required for treatment monitoring. PMID:25193011

  12. Lymphatic drainage and CTV in pancreatic carcinoma.

    PubMed

    Morganti, Alessio G; Cellini, Numa; Mattiucci, Gian Carlo; Macchia, Gabriella; Smaniotto, Daniela; Luzi, Stefano; Balducci, Mario; Deodato, Francesco; Valentini, Vincenzo; Trodella, Lucio

    2003-01-01

    CTV definition in exclusive or adjuvant radiation therapy of pancreatic carcinoma is essentially based on the opinion of "expert" authors and on the knowledge of lymphatic pathways. The subject has been widely debated. Radiotherapy treatments of the entire upper abdomen (liver and pancreatic region), pancreas and lymph node stations, to volumes focused on macroscopic tumor only, have been proposed. Carcinoma of exocrine pancreas is characterized by the frequent, early appearance of metastasis via the lymphatic route. Most commonly involved lymph node stations include those of the celiac trunk, superior mesenteric, peripancreatic, lumboaortic lymph nodes, those of the hepatic portal (the latter in particular for pancreatic head tumors) and of the hilum of spleen (the latter in particular for pancreatic tail tumors). The possible multicentricity of pancreatic carcinoma, most likely due to intraductal spread, should lead to the inclusion in the CTV of the entire pancreatic parenchyma. This should be considered also for the frequent perineural intra- or extrapancreatic spread of pancreatic carcinoma present also in small tumors (T1). In extrapancreatic spread the retropancreatic adipose tissue should be included in the CTV at least at the GTV level. At the present state of knowledge, in the absence of pattern of failure analysis and of comparison of different treatment approaches, in terms of the definition of volumes of interest, CTV definitions which include lymphatic drainage stations, most part of pancreatic parenchyma and retropancreatic adipose tissue seem justified especially in treatments for cure. In palliation, the CTV may be limited to the GTV and the adipose tissue behind it. PMID:15018319

  13. From ameloblast to iconoclast: Remembering Aubrey.

    PubMed

    Sinclair-Cohen, J

    2016-06-24

    The late Professor Aubrey Sheiham shaped dental public health as a discipline. He leaves behind cohorts of confident public health professionals in dentistry worldwide, including many former students, each with their own kaleidoscope of memories of him as teacher, mentor, colleague and friend. A paper that he published in The Lancet in 1977 famously challenged the prevailing paradigm on dental recalls. For such iconoclasm, I remember him as the dentist who dared disturb the universe. PMID:27338900

  14. Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

    PubMed

    Vitale, Alessandro; Farinati, Fabio; Burra, Patrizia; Trevisani, Franco; Giannini, Edoardo G; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Di Marco, Mariella; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Felder, Martina; Sacco, Rodolfo; Morisco, Filomena; Missale, Gabriele; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Chiaramonte, Maria; Spolverato, Gaya; Cillo, Umberto

    2015-10-01

    The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using the alpha-fetoprotein (AFP) model on the basis of AFP values and radiological size and number of nodules. The primary endpoint was the net health benefit (NHB), defined as LT survival benefit in quality-adjusted life years minus incremental costs (US $)/willingness to pay. The calculated median cost of non-LT therapies per patient was US $53,042 in Italy and US $62,827 in the United States. On Monte Carlo simulation, the NHB of LT was always positive for AFP model values ≤ 3 and always negative for values > 7 in both countries. A multivariate model showed that nontumor variables (patient's age, Child-Turcotte-Pugh [CTP] class, and alternative therapies) had the potential to shift the AFP model threshold of LT cost-ineffectiveness from 3 to 7. LT proved always cost-effective for HCC patients with AFP model values ≤ 3, whereas the cost-ineffectiveness threshold ranged between 3 and 7 using nontumor variables. PMID:26183802

  15. Identity-based High-performance thin Layer Chromatography Fingerprinting Profile and Tumor Inhibitory Potential of Anisochilus carnosus (L.f.) wall Against Ehrlich Ascites Carcinoma

    PubMed Central

    Gupta, Nilesh; Lobo, Richard; Kumar, Nimmy; Bhagat, Jay Kumar; Mathew, Jessy Elizabeth

    2015-01-01

    Context: Anisochilus carnosus (L.f.) wall belonging to the family Lamiaceae is a plant that is widely used in folk medicine for treating eczema, cold, cough, and fever. Objective: In the present study, we explored the anticancer potential of A. carnosus leaves against Ehrlich ascites carcinoma (EAC) and estimated the quantity of luteolin present in various extracts and fractions of A. carnosus by high-performance thin layer chromatography (HPTLC) fingerprinting. Materials and Methods: Various factors such as tumor volume, tumor cell viability, tumor weight, prolongation of lifespan, and hematological parameters were assessed. Result: We observed a significant lowering in tumor volume, tumor weight, and cell viability in EAC-induced mice following intervention with A. carnosus extracts. Also, there was a considerable prolongation of host lifespan and restoration of hematological parameters to almost normal levels with A. carnosus treatment. HPTLC fingerprinting of various extracts and fractions of A. carnosus along with luteolin as the reference standard revealed the occurrence of luteolin in all tested extracts and fractions of A. carnosus with the highest concentration being reported in the ethanol fraction. Conclusion: A. carnosus exhibits potent anti-tumor potential which can most likely be attributed to the occurrence of different phytochemicals such as phytosterols, terpenoids, and flavonoids in the plant. Further studies to isolate compounds from A. carnosus and understand the mechanism of anti-tumor activity would be worthwhile. SUMMARY EAC induced mice that received A. carnosus treatment exhibited significant reduction in tumor volume, tumor weight and tumor cell viability. Their life span was considerably prolonged. We detected luteolin in A. carnosus aqueous and ethanol extract using HPTLC. Hence, anticancer activity of A. carnosus can be partly attributed to the presence of luteolin. PMID:26929584

  16. Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy.

    PubMed

    Wang, Xiao-Bing; Jiang, Xing-Ran; Yu, Xi-Ying; Wang, Lin; He, Shun; Feng, Fei-Yue; Guo, Li-Ping; Jiang, Wei; Lu, Shih-Hsin

    2014-02-01

    Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.

  17. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011).

    PubMed

    Lau, Christine S M; Mahendraraj, Krishnaraj; Chamberlain, Ronald S

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973-2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival.

  18. Development of glycoprotein capture-based label-free method for the high-throughput screening of differential glycoproteins in hepatocellular carcinoma.

    PubMed

    Chen, Rui; Tan, Yexiong; Wang, Min; Wang, Fangjun; Yao, Zhenzhen; Dong, Liwei; Ye, Mingliang; Wang, Hongyang; Zou, Hanfa

    2011-07-01

    A robust, reproducible, and high throughput method was developed for the relative quantitative analysis of glycoprotein abundances in human serum. Instead of quantifying glycoproteins by glycopeptides in conventional quantitative glycoproteomics, glycoproteins were quantified by nonglycosylated peptides derived from the glycoprotein digest, which consists of the capture of glycoproteins in serum samples and the release of nonglycopeptides by trypsin digestion of captured glycoproteins followed by two-dimensional liquid chromatography-tandem MS analysis of released peptides. Protein quantification was achieved by comparing the spectrum counts of identified nonglycosylated peptides of glycoproteins between different samples. This method was demonstrated to have almost the same specificity and sensitivity in glycoproteins quantification as capture at glycopeptides level. The differential abundance of proteins present at as low as nanogram per milliliter levels was quantified with high confidence. The established method was applied to the analysis of human serum samples from healthy people and patients with hepatocellular carcinoma (HCC) to screen differential glycoproteins in HCC. Thirty eight glycoproteins were found with substantial concentration changes between normal and HCC serum samples, including α-fetoprotein, the only clinically used marker for HCC diagnosis. The abundance changes of three glycoproteins, i.e. galectin-3 binding protein, insulin-like growth factor binding protein 3, and thrombospondin 1, which were associated with the development of HCC, were further confirmed by enzyme-linked immunosorbent assay. In conclusion, the developed method was an effective approach to quantitatively analyze glycoproteins in human serum and could be further applied in the biomarker discovery for HCC and other cancers.

  19. An "in-electrode"-type immunosensing strategy for the detection of squamous cell carcinoma antigen based on electrochemiluminescent AuNPs/g-C3N4 nanocomposites.

    PubMed

    Wu, Lin; Hu, Yufang; Sha, Yuhong; Li, Wenrou; Yan, Tiantian; Wang, Sui; Li, Xing; Guo, Zhiyong; Zhou, Jun; Su, Xiurong

    2016-11-01

    A novel "in-electrode"-type electrochemiluminescence (ECL) immunosensor for the sensitive detection of squamous cell carcinoma antigen (SCCA) was constructed using magnetic graphene oxide (nanoFe3O4@GO) and Au nanoparticles/graphitic-phase carbon nitride (AuNPs/g-C3N4). The capture probe was prepared by immobilizing the primary antibody of SCCA (Ab1) on the nanoFe3O4@GO, while the AuNPs/g-C3N4 nanocomposites labelled the secondary antibody of SCCA (Ab2), which acted as a signal tag. The recognition scaffold was the following: the capture probe was immobilized onto the magnetic electrode surface that caught the target SCCA and finally allowed the immobilization of the signal tag via the interaction between antigen and antibody. Importantly, a high ECL signal could be obtained due to the unique immunocomplex, which ensured all of the g-C3N4 on the outmost plane were directly fixed onto the electrode surface and became part of the electrode surface. This resulted in an enhanced efficiency of the g-C3N4 for electrochemical luminescence, thus extending the outer Helmholtz plane (OHP) of the proposed electrode and leading to high sensitivity. Taking advantage of both nanoFe3O4@GO and AuNPs/g-C3N4, the ECL intensity was found to increase logarithmically with SCCA concentration in a wide linear range from 0.001 to 10ng/mL and with a detection limit of 0.4pg/mL. The proposed "in-electrode"-type ECL immunosensor was used to analyse SCCA in human serum, and satisfactory recoveries were obtained, indicating that the proposed method was promising for practical applications in the clinical diagnosis of SCCA. PMID:27591611

  20. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973–2011)

    PubMed Central

    Lau, Christine S. M.; Mahendraraj, Krishnaraj; Chamberlain, Ronald S.

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973–2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival. PMID:26663981

  1. Analysis of Epstein Barr Virus Encoded RNA Expression in Nasopharyngeal Carcinoma in North-Eastern India: A Chromogenic in Situ Hybridization Based Study

    PubMed Central

    Saikia, Anjan; Raphael, Vandana; Shunyu, N-Brian; Khonglah, Yookarin; Mishra, Jaya; Jitani, Ankit-Kumar; Medhi, Jayanta

    2016-01-01

    Introduction: Nasopharyngeal carcinoma (NPC) is a common cancer in the North-East region of India. Though the role of environmental contributors of NPC in the North-Eastern part of India is firmly established, EBV as an etiological agent in the region remains unexplored. Material and Methods: Fifty-one patients, who presented at the department of ENT, NEIGRIHMS and were confirmed as NPC upon histopathological examination, were included in the study. Chromogenic in-situ hybridization (CISH) was used for the evaluation of EBER (Epstein Barr Virus Encoded RNA). Presence of nuclear signals was taken as positive for EBER expression. EBER status was correlated with various clinicopathological parameters like age, sex, dietary habits, histological types of NPC, and ethnicity of the patients. Results: The age range of the study group was 25 to 70 years with a mean age of 44.64 years and a male:female ratio of 3:2. Non-keratinizing undifferentiated type of NPC was the most common histological type. EBV was positive in 59% (30/51) of our cases. It showed a statistically significant correlation with the Naga community (P=0.01), with consumption of smoked food (P=0.02), and cigarette smoking (P=0.02). There was no correlation of EBV with age, sex, lymph node metastasis, stage, and histology. Conclusion: Our result indicates that EBV may be an additional risk factor in the pathogenesis of NPC in this region of India. So apart from lifestyle modification, a future study for a screening test for EBV viral load even in asymptomatic patients may be considered, for determination of disease susceptibility, early diagnosis, and proper management. PMID:27602338

  2. Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

    PubMed

    Vitale, Alessandro; Farinati, Fabio; Burra, Patrizia; Trevisani, Franco; Giannini, Edoardo G; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Di Marco, Mariella; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Felder, Martina; Sacco, Rodolfo; Morisco, Filomena; Missale, Gabriele; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Chiaramonte, Maria; Spolverato, Gaya; Cillo, Umberto

    2015-10-01

    The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using the alpha-fetoprotein (AFP) model on the basis of AFP values and radiological size and number of nodules. The primary endpoint was the net health benefit (NHB), defined as LT survival benefit in quality-adjusted life years minus incremental costs (US $)/willingness to pay. The calculated median cost of non-LT therapies per patient was US $53,042 in Italy and US $62,827 in the United States. On Monte Carlo simulation, the NHB of LT was always positive for AFP model values ≤ 3 and always negative for values > 7 in both countries. A multivariate model showed that nontumor variables (patient's age, Child-Turcotte-Pugh [CTP] class, and alternative therapies) had the potential to shift the AFP model threshold of LT cost-ineffectiveness from 3 to 7. LT proved always cost-effective for HCC patients with AFP model values ≤ 3, whereas the cost-ineffectiveness threshold ranged between 3 and 7 using nontumor variables.

  3. Acquired Hypothyroidism as a Predictive Marker of Outcome in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors: A Literature-Based Meta-Analysis.

    PubMed

    Nearchou, Andreas; Valachis, Antonis; Lind, Pehr; Akre, Olof; Sandström, Per

    2015-08-01

    Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution.

  4. Survival Benefits of Small Anatomical Resection of the Liver for Patients with Hepatocellular Carcinoma and Impaired Liver Function, Based on New-Era Imaging Studies

    PubMed Central

    Sakoda, Masahiko; Ueno, Shinichi; Iino, Satoshi; Hiwatashi, Kiyokazu; Minami, Koji; Kawasaki, Yota; Kurahara, Hiroshi; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Natsugoe, Shoji

    2016-01-01

    Background: It has been reported that anatomical resection of the liver may be preferred for primary hepatocellular carcinoma (HCC), and is at least recommended for systematic removal of a segment confined by tumor-bearing portal tributaries. However, nonanatomical resection (NAR) is often selected because of the patient's background, impairment of liver function, and tumor factors. The aims of the present study were to retrospectively compare the recurrence-free survival (RFS) rates for cases of partial resection (PR) and for small anatomical resection (SAR), which is regarded as NAR for primary HCC with impaired liver function. Patients and Methods: So-called NAR was performed for a primary and solitary (≤ 5cm) HCC in 47 patients; the patients were classified into PR (n=25) and SAR (n=22) groups. Clinicopathological factors, survival data, and recurrence patterns were compared between groups. Results: There were no significant differences in the preoperative characteristics between the two groups. Operative time was significantly longer in the SAR group than in the PR group. There was no significant difference in the postoperative morbidity and tumor pathological characteristics between the two groups. The RFS of the SAR group was significantly better than those of the PR group. Although there was no significant difference in the pattern of recurrence between the two groups, the rate of intrahepatic recurrence in the same segment as the initial tumor tended to be higher in the PR group than in the SAR group. Multivariate analysis revealed that only the PR operative procedure was significant independent risk factor for poorer RFS. Conclusion: Compared with PR, SAR effectively improves the rate of RFS after surgery for a primary and solitary HCC with impaired liver function. PMID:27326244

  5. Hepatocellular Carcinoma (HCC)

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  6. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Di Bisceglie, Adrian M.

    2005-01-01

    Hepatocellular carcinoma (HCC) is responsible for a large proportion of cancer deaths worldwide. HCC is frequently diagnosed after the development of clinical deterioration at which time survival is measured in months. Long-term survival requires detection of small tumors, often present in asymptomatic individuals, which may be more amenable to invasive therapeutic options. Surveillance of high-risk individuals for HCC is commonly performed using the serum marker alfa-fetoprotein (AFP) often in combination with ultrasonography. Various other serologic markers are currently being tested to help improve surveillance accuracy. Diagnosis of HCC often requires more sophisticated imaging modalities such as CT scan and MRI, which have multiphasic contrast enhancement capabilities. Serum AFP used alone can be helpful if levels are markedly elevated, which occurs in fewer than half of cases at time of diagnosis. Confirmation by liver biopsy can be performed under circumstances when the diagnosis of HCC remains unclear. PMID:18333158

  7. Prevention of Hepatocellular Carcinoma

    PubMed Central

    Schütte, Kerstin; Balbisi, Fathi; Malfertheiner, Peter

    2016-01-01

    The epidemiology of hepatocellular carcinoma (HCC) has significantly changed throughout the past decade and will continue to do so in the future as a consequence of effective primary prevention and treatment of virus-related liver diseases. However, other risk factors for HCC are constantly on the rise, including alcoholic liver disease and nonalcoholic fatty liver disease. The knowledge on these and further risk factors associated with an increased risk of HCC provide the opportunity and chance for the development and implementation of successful preventive strategies to decrease the worldwide burden of HCC. This mini-review gives a short overview on current strategies in primary, secondary, and tertiary prevention of HCC. PMID:27722155

  8. Salivary gland myoepithelial carcinoma.

    PubMed

    Vilar-González, S; Bradley, K; Rico-Pérez, J; Vogiatzis, P; Golka, D; Nigam, A; Sivaramalingam, M; Kazmi, S

    2015-11-01

    Salivary gland myoepithelial carcinoma (MC) or malignant myoepithelioma is a rare entity. MC usually presents as a slow-growing painless mass arising in the parotid gland, but may involve other salivary glands. This tumour may be particularly locally aggressive, but its clinical and biological features are not yet fully understood. MC may arise from pre-existing benign lesions, such as pleomorphic adenomas or benign myoepitheliomas, or may arise de novo. It usually affects patients over 50 years old, with no gender preference. Because it is often asymptomatic, the presentation and diagnosis can be delayed by months, even years. The current WHO classification considers MC to be an intermediate- to high-grade malignancy. Other published data suggest it is likely to be a high-grade neoplasm, consistent with its aggressive behaviour. Its epidemiology, histopathological features, immunohistochemical profile, clinical behaviour and optimal management are not well understood. Following review of the current literature we aim to address these.

  9. Treatment Option Overview (Adrenocortical Carcinoma)

    MedlinePlus

    ... of Childhood Treatment for more information.) Having certain genetic conditions increases the risk of adrenocortical carcinoma. Anything ... can be a sign of disease. CT scan (CAT scan) : A procedure that makes a series of ...

  10. Stages of Merkel Cell Carcinoma

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  11. Onychocytic carcinoma: a new entity.

    PubMed

    Perrin, Christophe; Langbein, Lutz; Ambrossetti, Damien; Erfan, Nouran; Schweizer, Jürgen; Michiels, Jean-François

    2013-08-01

    We have recently described a new nail tumor known as onychocytic matricoma. Herein, we describe its malignant counterpart. Clinically, the tumor simulates onychomatricoma (OM). Histologically, this in situ malignant epithelial tumor exhibits a distinct picture of onychocytic differentiation with signs of both nail matrical differentiation and nail plate differentiation. We have proposed the name onychocytic carcinoma for this singular adnexal neoplasm. Given the peculiar thickening of the nail plate observed in OM, onychocytic matricoma, and onychocytic carcinoma, the clinical individualization of a new type of nail band pattern could be proposed. It presents as an acquired localized (monodactylous) longitudinal pachyonychia. Such longitudinal pachyonychia allow the recognition of the matrical nail tumor, which has a limited etiological spectrum. Xantholeucopachyonychia suggests mainly OM and rarely onychocytic carcinoma. Pachymelanonychia suggests onychocytic matricoma and rarely pigmented OM or onychocytic carcinoma. PMID:23518638

  12. Cutaneous metastases of hepatocellular carcinoma.

    PubMed

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  13. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    ... radiation. Exposure to radiation can lead to skin cancers. ... DG, Farndon PA. Nevoid basal cell carcinoma syndrome. 2002 Jun 20 ... al. eds. Cancer of the Skin. 2nd ed. Philadelphia, PA: Elsevier ...

  14. [Bronchial mucoepidermoid carcinoma].

    PubMed

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible. PMID:12602035

  15. Cholangiographic evaluation of bile duct carcinoma

    SciTech Connect

    Nichols, D.A.; MacCarty, R.L.; Gaffey, T.A.

    1983-12-01

    Cholangiograms and clinical histories of 82 patients with biopsy-proved bile duct carcinoma were reviewed. The carcinomas were classified according to morphologic findings and clinical outcome. Ulcerative colitis and antecedent inflammatory disease of the biliary tree, particularly primary sclerosing cholangitis, seem to predispose to the development of bile duct carcinoma. Focal stenotic lesions were the most common morphologic type (62/82). Polypoid carcinomas and diffuse sclerosing carcinomas were less common and of about equal frequency. Prognosis was best for patients with polypoid carcinomas and worst for those with diffuse sclerosing carcinomas. In 69 cases (84%), the tumors involved the intrahepatic or proximal extrahepatic ducts, makin curative resection difficult or impossible. Patients with carcinomas limited to the more distal extrahepatic bile ducts had a longer average survival and a higher probability of surgical cure. Proper management of patients with bile duct carcinoma requires a complete and accurate cholangiographic evaluation of the morphology, location, and extent of the disease.

  16. Microvascular invasion in hepatocellular carcinoma

    PubMed Central

    Ünal, Emre; İdilman, İlkay Sedakat; Akata, Deniz; Özmen, Mustafa Nasuh; Karçaaltıncaba, Muşturay

    2016-01-01

    Microvascular invasion is a crucial histopathologic prognostic factor for hepatocellular carcinoma. We reviewed the literature and aimed to draw attention to clinicopathologic and imaging findings that may predict the presence of microvascular invasion in hepatocellular carcinoma. Imaging findings suggesting microvascular invasion are disruption of capsule, irregular tumor margin, peritumoral enhancement, multifocal tumor, increased tumor size, and increased glucose metabolism on positron emission tomography-computed tomography. In the presence of typical findings, microvascular invasion may be predicted. PMID:26782155

  17. Gene therapy and nasopharyngeal carcinoma.

    PubMed

    Hughes, J; Alusi, G; Wang, Y

    2012-06-01

    In 2003, a non-replicating adenoviral gene therapy product received the world`s first government licence for the treatment of head and neck cancer. Two years later approval was granted to a replication-selective adenovirus for the treatment of nasopharyngeal carcinoma in combination with chemotherapy. This review introduces the reader to gene therapy as an emerging treatment modality, and outlines its application to the management of nasopharyngeal carcinoma by examining recent pre-clinical and clinical research.

  18. Multiple oncocytomas and renal carcinoma

    SciTech Connect

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma.

  19. [Adenosquamous carcinoma of the palate].

    PubMed

    Mancusi, G; Susani, M; Kornfehl, J; Girsch, W; Kautzky, M

    2002-08-01

    A rare case of adenosquamous carcinoma in a 74 year-old man is reported. Presenting as a nodule on the soft palate, diagnosis was prolonged because of the benign macroscopic aspect. CT-scan and MR-tomography showed an encapsulated lesion but biopsy and histologic examination revealed the typical features of adenosquamous carcinoma. The tumour consisted of adenocarcinoma and squamous cell carcinoma in close proximity to minor salivary glands of which the tumour seemed to have its origin. This entity, although rare in the head and neck region has been documented to be very aggressive with early regional and hematogenic metastasis. Therefore it has to be distinguished from other tumours, especially from mucoepidermoid carcinomas of the salivary glands, which have a better prognosis. Adenosquamous carcinoma is considered to have poor radiosensitivity and chemotherapeutic approaches have also not been successful in the literature. In our case radical surgical therapy was performed by excision of the whole soft palate and bilateral neck dissection. This resulted in total removal of the tumour but revealed bilateral lymph node metastases. Vital functions were saved by reconstruction of the palate with a free vascularized tensor-fasciae-latae-perforator-flap. For the first time in a case of adenosquamous carcinoma carcinoembryonic antigen in serum was monitored. A pretherapeutical 29-fold elevation resulted in a marked decrease after surgery, but supranormal values indicated remaining tumour burden which was found in metastases in the lung. Because of the limitations in therapy, early histologic diagnosis is most important in this highly malignant tumour.

  20. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  1. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  2. Lymphoepithelial carcinoma of the minor salivary gland.

    PubMed

    Worley, N K; Daroca, P J

    1997-06-01

    Undifferentiated carcinoma of the minor salivary glands has been rarely reported in the world literature. Lymphoepithelial carcinoma, which is a variant of undifferentiated carcinoma, is distinguished from small cell and large cell undifferentiated carcinoma by its association with benign lymphoepithelial lesions. We report a case of a lymphoepithelial carcinoma developing in a minor salivary gland of the oral cavity in a 69-year-old woman. To our knowledge, this is the first reported case of a lymphoepithelial carcinoma arising from a minor salivary gland.

  3. Inflammatory Breast Carcinoma Presenting with Two Different Patterns of Cutaneous Metastases: Carcinoma Telangiectaticum and Carcinoma Erysipeloides

    PubMed Central

    Yaghoobi, Reza; Talaizade, Abdolhasan; Lal, Karan; Ranjbari, Nastaran; Sohrabiaan, Nasibe

    2015-01-01

    Cutaneous metastases can have many different clinical presentations. They are seen in patients with advanced malignant disease; however, they can be the initial manifestation of undetected malignancies. Inflammatory breast carcinoma is a rare and aggressive form of breast cancer that has a nonspecific appearance mimicking many benign conditions including mastitis, breast abscesses, and/or dermatitis. The authors report the case of a 40-year-old woman with inflammatory breast carcinoma presenting with violaceous papulovesicular lesions resembling lymphangioma circumscriptum and erythematous patches resembling erysipelas. These lesions represent two different types of cutaneous metastases, both of which were the initial signs of inflammatory breast carcinoma in the patient described herein. Skin biopsy of lesions confirmed invasive breast cancer and further prompted a work up for inflammatory breast carcinoma. This case demonstrates the importance of follow-up for all breast lesions, even those considered to be of benign nature, for they can be presenting signs of metastatic breast cancer. PMID:26345728

  4. Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for 89Zr4+ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

    PubMed Central

    N.Tinianow, Jeff; Pandya, Darpan N.; Pailloux, Sylvie L.; Ogasawara, Annie; Vanderbilt, Alexander N.; Gill, Herman S.; Williams, Simon-P.; Wadas, Thaddeus J.; Magda, Darren; Marik, Jan

    2016-01-01

    A novel octadentate 3-hydroxypyridin-2-one (2,3-HOPO) based di-macrocyclic ligand was evaluated for chelation of 89Zr; subsequently, it was used as a bi-functional chelator for preparation of 89Zr-labeled antibodies. Quantitative chelation of 89Zr4+ with the octadentate ligand forming 89ZrL complex was achieved under mild conditions within 15 minutes. The 89Zr-complex was stable in vitro in presence of DTPA, but a slow degradation was observed in serum. In vivo, the hydrophilic 89Zr-complex showed prevalently renal excretion; and an elevated bone uptake of radioactivity suggested a partial release of 89Zr4+ from the complex. The 2,3-HOPO based ligand was conjugated to the monoclonal antibodies, HER2-specific trastuzumab and an isotypic anti-gD antibody, using a p-phenylene bis-isothiocyanate linker to yield products with an average loading of less than 2 chelates per antibody. Conjugated antibodies were labeled with 89Zr under mild conditions providing the PET tracers in 60-69% yield. Despite the limited stability in mouse serum; the PET tracers performed very well in vivo. The PET imaging in mouse model of HER2 positive ovarian carcinoma showed tumor uptake of 89Zr-trastuzumab (29.2 ± 12.9 %ID/g) indistinguishable (p = 0.488) from the uptake of positive control 89Zr-DFO-trastuzumab (26.1 ± 3.3 %ID/g). In conclusion, the newly developed 3-hydroxypyridin-2-one based di-macrocyclic chelator provides a viable alternative to DFO-based heterobifunctional ligands for preparation of 89Zr-labeled monoclonal antibodies for immunoPET studies. PMID:26941844

  5. National Incidence, Management and Survival of Urachal Carcinoma

    PubMed Central

    Collins, Dearbhaile C.; Velázquez-Kennedy, Kyra; Deady, Sandra; Brady, Adrian P.; Sweeney, Paul; Power, Derek G.

    2016-01-01

    Urachal carcinoma is an uncommon cancer whose rarity has precluded its study and evidence-based management strategies are lacking. This study assessed all urachal carcinomas in Ireland and clinical parameters in order to improve understanding. Urachal carcinomas diagnosed from 1994 to 2011 were identified from the National Cancer Registry in Ireland. Data obtained included patient age, gender, diagnostic year, pathology, tumor stage, patient treatment strategies and survival. Twenty-six urachal carcinomas were identified, the majority being adenocarcinoma. This comprised 0.3% of all invasive bladder tumors. Patients were predominantly male (62%) and over 50 years of age (58%). Twenty-two patients (85%) underwent surgery, with only six (23%) undergoing chemotherapy. On average, median overall survival was 2.6 years (range 0-15.2 yrs). Survival was longer in women (5 vs. 1.9 yrs), patients under 50 years of age (3.6 vs. 1.9 yrs), those without confirmed metastasis (4.1 vs. 0.7 yrs) and those who received chemotherapy (3.6 vs. 2.6 yrs). The overall survival of urachal carcinoma in Ireland is less than expected from published literature. This study highlights the need for centralization of rare tumors with international collaboration to identify the optimal treatment strategy and improve outcome. PMID:27746878

  6. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    PubMed Central

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  7. Silica, pneumoconiosis and carcinoma of the lung

    SciTech Connect

    Heppleston, A.G.

    1985-01-01

    The author explains the possible relationship between exposure to mineral dust with a high silica content and the development of bronchogenic carcinoma. Studies to date accept that lung cancer is a risk associated with exposure to siliceous dust. The author has sought to establish arguments to refute this theory and has accumulated observations based on practical experiences with miners which indicate that silica does not possess this carcinogenic role. The above mentioned observations take the form of medical examinations or autopsies on mine workers in different countries. 72 references.

  8. [The historical development of resection surgery in pancreatic carcinoma].

    PubMed

    Sulkowski, U; Meyer, J; Reers, B; Pinger, P; Waldner, M

    1991-01-01

    Based on the pitfalls of the past the development of pancreatic resection therapy is outlined, starting with the first distal pancreatic resection in 1882 performed by Trendelenburg. Giving details of operations from the first decades of this century the Whipple operation is described as the early cornerstone in the history of radical therapy of pancreatic cancer. Summarizing the disappointments of the seventies gives the clue to the present situation with a modified Whipple operation as the standard curative approach to pancreatic carcinoma today. Additionally, various aspects of palliative therapy for pancreatic carcinoma are discussed.

  9. [Oncocytic carcinoma of the parotid gland: a case report].

    PubMed

    Jiang, Richeng; Wang, Xin; Tong, Lingling

    2015-07-01

    Approximately 3% of all head and neck neoplasms originate in the parotid gland and less than 1% are oncocytic. We present the rare case of a 63-year-old woman with oncocytic carcinoma of the parotid gland with facial nerve invasion and discuss the characteristics of this rare entity. Based on the results of medical history, physical examination, computed tomography and postoperative histopathological diagnosis, oncocytic carcinoma of the parotid gland was diagnosed. Treatment involved complete parotid gland removal and right neck dissection. Adjuvant radiotherapy and chemotherapy were followed by operation. As of 9 months following surgery, no recurrence has been identified, but long-term results are undefined. PMID:26540931

  10. Non-functional parathyroid carcinoma: a case report and review of the literature

    PubMed Central

    Wang, Liang; Han, Dali; Chen, Wanjun; Zhang, Shuguang; Wang, Zhiqi; Li, Ke; Gao, Yongsheng; Zou, Shujuan; Yang, Aiju

    2015-01-01

    Non-functional parathyroid carcinoma is an exceedingly rare disease with 31 reported cases since 1909. Because of the scarce number of cases of non-functional parathyroid carcinoma, there are no evidence-based recommendations for its optimal treatment. Surgery, including en bloc resection of the carcinoma, ipsilateral thyroid lobe and isthmus together with a neck dissection only in case of lymph node involvement, is the main treatment for non-functioning parathyroid carcinoma. The patient usually has a poorer prognosis because of detection at advanced stages, the relative ineffectiveness of adjuvant treatment modalities and the lack of adequate parameters for clinical follow-up. In this report, we present a case of non-functional parathyroid carcinoma at our institution, and we review the previous literature to discuss the latest advances in the diagnosis and treatment of this rare disease. PMID:26408508

  11. Pituitary carcinoma with intraspinal metastasis: report of two cases and review of the literature

    PubMed Central

    Wang, Yin Qian; Fan, Tao; Zhao, Xin Gang; Liang, Cong; Qi, Xue Ling; Li, Jian Yi

    2015-01-01

    Pituitary carcinomas are rare malignant neoplasms with diagnostic and management challenges. Patients with pituitary carcinomas have extremely poor outcomes. In this report, the authors describe two cases of pituitary carcinomas with intraspinal metastasis (Case 1: 42-year-old man with a history of pituitary adenoma 16 years ago developed an intraspinal lesion at C4-C5; Case 2: 26-year-old women with a history of growth hormone-producing pituitary adenoma 9 years ago developed intraspinal lesion in the sacral canal). Both patients underwent spine surgery. The intraspinal lesions were confirmed as metastatic pituitary carcinomas based on the histomorphology and immunohistochemical stains. The authors reviewed the literature for the diagnosis, treatment, and prognosis of intraspinal metastasis from pituitary carcinomas. PMID:26464743

  12. Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).

    PubMed

    Offman, Saul L; Longacre, Teri A

    2012-09-01

    Clear cell carcinoma has a storied history in the female genital tract. From the initial designation of ovarian clear cell adenocarcinoma as "mesonephroma" to the linkage between vaginal clear cell carcinoma and diethylstilbestrol exposure in utero, gynecologic tract clear cell tumors have puzzled investigators, posed therapeutic dilemmas for oncologists, and otherwise presented major differential diagnostic challenges for pathologists. One of the most common errors in gynecologic pathology is misdiagnosis of clear cell carcinoma, on both frozen section and permanent section. Given the poor response to platinum-based chemotherapy for advanced-stage disease and increased risk of thromboembolism, accurate diagnosis of clear cell carcinoma is important in the female genital tract. This review (1) presents the clinical and pathologic features of female genital tract clear cell carcinomas; (2) highlights recent molecular developments; (3) identifies areas of potential diagnostic confusion; and (4) presents solutions for these diagnostic problems where they exist.

  13. Sebaceous Carcinoma of the Parotid Gland: A Case Report

    PubMed Central

    Takada, Yohei; Kawamoto, Kohei; Baba, Susumu; Takada, Tomoko; Inoue, Toshiya; Tomoda, Koichi

    2015-01-01

    Background Primary sebaceous carcinoma of the parotid gland is extremely rare, and because of its rarity, clinicopathological characteristics and histogenesis are not fully understood. Methods Here, we report a patient who presented with a left infra-auricular painless mass. We present the histological features and discuss possible optimal treatments based on previous literature. Results The mass was suspected to be a myoepithelial tumor or possibly a pleomorphic adenoma. Initially, the mass was resected with preservation of the facial nerve, but this caused facial palsy. Because the histological examination showed a sebaceous carcinoma and a part of the mass could be remaining on the facial nerve, additional surgery was performed, and the facial nerve was reconstructed with cervical nerve. Follow-up after 7 months showed no sign of recurrence of metastasis. Conclusion We encountered a rare sebaceous carcinoma of the parotid gland. Additional surgery was performed because preoperative diagnosis was difficult. PMID:25848361

  14. Small cell carcinoma of the cervix: a case report.

    PubMed

    Korcum, Aylin Fidan; Aksu, Gamze; Bozcuk, Hakan; Pestereli, Elif; Simsek, Tayup

    2008-04-01

    Small cell carcinoma of the uterine cervix accounts for 1-3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.

  15. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  16. A Novel Inflammation- and Nutrition-Based Prognostic System for Patients with Laryngeal Squamous Cell Carcinoma: Combination of Red Blood Cell Distribution Width and Body Mass Index (COR-BMI)

    PubMed Central

    Chen, Shiqi; Yang, Ankui; Zhang, Quan

    2016-01-01

    Background Laryngeal squamous cell carcinoma (LSCC) is a head and neck cancer type. In this study, we introduced a novel inflammation- and nutrition-based prognostic system, referred to as COR-BMI (Combination of red blood cell distribution width and body mass index), for LSCC patients. Methods A total of 807 LSCC patients (784 male and 23 female, 22–87 y of age) who underwent surgery were enrolled in this retrospective cohort study. The patients were stratified by COR-BMI into three groups: COR-BMI (0) (RDW ≤ 13.1 and BMI ≥ 25); COR-BMI (1) (RDW ≤ 13.1 and BMI < 18.5 or 18.5 ≤ BMI < 25; RDW > 13.1 and 18.5 ≤ BMI < 25 or BMI ≥ 25); or COR-BMI (2) (RDW > 13.1 and BMI < 18.5). Cox regression models were used to investigate the association between COR-BMI and cancer-specific survival (CSS) rate among LSCC patients. Results The 5-y, 10-y, and 15-y CSS rates were 71.6%, 60.1%, and 55.4%, respectively. There were significant differences among the COR-BMI groups in age (< 60 versus ≥ 60 y; P = 0.005) and T stage (T1, T2, T3, or T4; P = 0.013). Based on the results, COR-BMI (1 versus 0: HR = 1.76; 95% CI = 0.98–3.15; 2 versus 0: HR = 2.91; 95% CI = 1.53–5.54, P = 0.001) was a significant independent predictor of CSS. Conclusion COR-BMI is a novel inflammation- and nutrition-based prognostic system, which could predict long-term survival in LSCC patients who underwent surgery. PMID:27658208

  17. Translating the molecular diversity of hepatocellular carcinoma into clinical practice

    PubMed Central

    Schulze, Kornelius; Zucman-Rossi, Jessica

    2016-01-01

    abstract Deciphering genomic diversity could improve clinical care for patients with hepatocellular carcinoma. Recently, our study group identified 161 putative driver genes and 2 new mutational signatures, and demonstrated that 28% of patients harbor targetable alterations. This could be the first promising step in the development of genome-based clinical trials. PMID:27652310

  18. Translating the molecular diversity of hepatocellular carcinoma into clinical practice.

    PubMed

    Schulze, Kornelius; Zucman-Rossi, Jessica

    2016-07-01

    Deciphering genomic diversity could improve clinical care for patients with hepatocellular carcinoma. Recently, our study group identified 161 putative driver genes and 2 new mutational signatures, and demonstrated that 28% of patients harbor targetable alterations. This could be the first promising step in the development of genome-based clinical trials. PMID:27652310

  19. Treatment Options for Thymoma and Thymic Carcinoma

    MedlinePlus

    ... symptoms of thymoma and thymic carcinoma include a cough and chest pain. Thymoma and thymic carcinoma may ... if you have any of the following: A cough that doesn't go away. Chest pain. Trouble ...

  20. Stages of Thymoma and Thymic Carcinoma

    MedlinePlus

    ... symptoms of thymoma and thymic carcinoma include a cough and chest pain. Thymoma and thymic carcinoma may ... if you have any of the following: A cough that doesn't go away. Chest pain. Trouble ...

  1. General Information about Merkel Cell Carcinoma

    MedlinePlus

    ... Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. General Information about Thymoma and Thymic Carcinoma

    MedlinePlus

    ... and Thymic Carcinoma Treatment (PDQ®)–Patient Version General Information About Thymoma and Thymic Carcinoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  4. A Rare Presentation of Primary Nasopharyngeal Carcinoma (NPC) in Mediastinum

    PubMed Central

    Fathi, Afshin; Amani, Firuz; Davoodi, Mohammad; Bahadoram, Sara; Bahadoram, Mohammad

    2016-01-01

    Introduction Nasopharyngeal carcinoma among the children has been rare accounting for only 1% of all pediatric malignancies. Both genetic and environmental factors have contributed to the development of nasopharyngeal carcinoma. Among the children there was a higher rate of undifferentiated histology. The mean age of nasopharyngeal carcinoma diagnosis has been 11 years old age; and the most common site was nasopharynx. Palpable lymphadenopathy, dysphasia and neural defect were common associated signs. Case Presentation A 15-year-old boy has presented with a mass that located near by the heart in the left side of mediastinum with invasion to anterior mediastinum from two years ago. In biopsy, nasopharyngeal carcinoma, non-keratinizing type, has diagnosed while there was no involvement of nasopharyngeal region. Patient has treated by 70 Gy (2.0 Gy/fraction) radiotherapy plus concomitant chemotherapy with base of docetaxel. But the mass had no regression. Then, the patient has treated with Cisplatin 100 mg/m2 IV on days 1, 22, and 43 with radiation, then cisplatin 80 mg/m2 IV on day 1 plus fluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1 - 4 every 4wk for 3 cycles and after remission interferon beta has added to treatment for 6 months duration as a maintenance therapy. After 1 year follow up; the patient was in complete remission. In the course of therapy, only hypothyroidism has occurred. Conclusions Nasopharyngeal carcinoma in childhood, without nasopharyngeal involvement, initially could be detected in other sites such as pericardium. Also good results could be respected by cisplatin and 5-fluorouracil based neoadjuvant chemotherapy before radiotherapy plus interferon beta as a maintenance therapy in childhood aggressive nasopharyngeal carcinoma. PMID:27761207

  5. Carcinoma of endocrine organs: results of the RARECARE project.

    PubMed

    van der Zwan, Jan Maarten; Mallone, Sandra; van Dijk, Boukje; Bielska-Lasota, Magdalena; Otter, Renée; Foschi, Roberto; Baudin, Eric; Links, Thera P

    2012-09-01

    The rarity or the asymptomatic character of endocrine tumours results in a lack of epidemiological studies on their incidence and survival patterns. The aim of this study was to describe the incidence, prevalence and survival of endocrine tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) with follow-up until 31st December 2003. These data give an unique overview of the burden of endocrine carcinomas in Europe. A list of tumour entities based on the third International Classification of Diseases for Oncology was provided by the project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594 cases of endocrine carcinomas were analysed in this study. Incidence rates increased with age and were highest in patients 65 years of age or older. In 2003, more than 315,000 persons in the EU (27 countries) were alive with a past diagnosis of a carcinoma of endocrine organs. The incidence of pituitary carcinoma equalled four per 1,000,000 person years and showed the strongest decline in survival with increasing age. Thyroid cancer showed the highest crude incidence rates (four per 100,000 person years) and was the only entity with a gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the rarest endocrine entity with two new cases per 10,000,000 person years. For adrenal carcinoma, the most remarkable observations were a higher survival for women compared to men (40% compared to 32%, respectively) and a particularly low relative survival of 24% in patients 65 years of age or older. More high quality studies on rare cancers, with additional information, e.g. on stage and therapeutic approach, are needed and may be of help in partly explaining the observed variation in survival.

  6. Hepatocellular carcinoma in India.

    PubMed

    Bhattacharyya, Gouri Shankar; Babu, K Govind; Malhotra, Hemant; Ranade, Anantbhushan A; Murshed, Shaiqua; Datta, Debasis

    2013-12-01

    Cancers of the liver are one of the commonest cancers that occur in the world, the commonest of which is the hepatocellular carcinoma (HCC). It is considered to be the 5th commonest cancer in the world. In the areas that are endemic for hepatitis B and C, it is extremely common. Unfortunately, India which is an endemic zone for hepatitis B, there has been no comprehensive analyzed data for HCC. Incidence of HCC in India occurs at two peaks, one at a young age between 40 to 55 years and another above 60 years. Eighty per cent of all HCCs occurring in India occur with cirrhosis of liver in the background and 60% of all these cases are hepatitis B positive carriers. Symptoms are reflective of late presentation with advanced disease. Surgery, the only curative modulus available, unfortunately is not possible in 95% of HCC patients. Majority of the patients are treated with palliative and supportive care and life spans are limited. Sorafenib is used in a small section of patients. Characterization of HCC with molecular sub-typing is the need of the hour.

  7. [External radiotherapy for hepatocellular carcinoma].

    PubMed

    Girard, N; Mornex, F

    2011-02-01

    For a long time radiotherapy has been excluded from the therapeutic strategy for hepatocellular carcinoma, given its significant toxicity on the non-tumoral liver parenchyma. Conformal radiation is a recent advance in the field of radiotherapy, allowing dose escalation and combination with other therapeutic options for hepatocellular carcinoma, including trans-arterial chemo-embolization. Conformal radiotherapy is associated with interesting features, especially in cirrhotic patients: wide availability, non-invasiveness, possibility to target multiple localizations anywhere within the liver parenchyma, and favorable tolerance profile even in patients with cirrhosis and/or in a poor medical condition. Recently, radiation delivery has been optimized through several technical developments: respiratory gating and intensity-modulated radiotherapy, which allow a better focalization of the ballistics, stereotactic techniques and proton-beam radiotherapy, whose availability is currently limited in Europe. Given the high response rates of hepatocellular carcinoma to radiation, conformal radiotherapy may be regarded as a curative-intent treatment for hepatocellular carcinoma, similar to surgery and per-cutaneous techniques. Yet the impact of radiotherapy has to be evaluated in randomized trials to better integrate in the complex therapeutic algorithm of hepatocellular carcinoma.

  8. Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

    ClinicalTrials.gov

    2016-06-14

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Oral Cavity Adenoid Cystic Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Oral Cavity Adenoid Cystic Carcinoma

  9. Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

    PubMed

    Erickson, D R; Dabbs, D J; Olt, G J

    1996-05-01

    In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

  10. Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy

    PubMed Central

    2014-01-01

    Background Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) receiving platinum-based chemotherapy as their first-line treatment have a dismal prognosis, with a median overall survival (OS) of ~7 months. Methotrexate is sometimes used following platinum failure or in patients not fit enough for platinum therapy, but this agent has not demonstrated any OS improvement. Targeted therapies are a novel approach, with the EGFR-targeting monoclonal antibody cetuximab (plus platinum-based chemotherapy) approved in the US and Europe in the first-line R/M setting, and as monotherapy following platinum failure in the US. However, there is still a high unmet medical need for new treatments that improve outcomes in the second-line R/M setting following failure on first-line platinum-containing regimens. Afatinib, an irreversible ErbB family blocker, was recently approved for the first-line treatment of EGFR mutation-positive metastatic non-small cell lung cancer. Afatinib has also shown clinical activity similar to cetuximab in a Phase II proof-of-concept HNSCC trial. Based on these observations, the Phase III, LUX-Head & Neck 1 study is evaluating afatinib versus methotrexate in R/M HNSCC patients following progression on platinum-based chemotherapy in the R/M setting. Methods/Design Patients with progressive disease after one first-line platinum-based chemotherapy are randomised 2:1 to oral afatinib (starting dose 40 mg once daily) or IV methotrexate (starting dose 40 mg/m2 once weekly) administered as monotherapy with best supportive care until progression or intolerable adverse events. Efficacy of afatinib versus methotrexate will be assessed in terms of progression-free survival (primary endpoint). Disease progression will be evaluated according to RECIST v1.1 by investigator and independent central review. Secondary endpoints include OS, tumour response and safety. Health-related quality of life and biomarker assessments will

  11. Treatment of thyroid follicular carcinoma.

    PubMed

    Ríos, Antonio; Rodríguez, José M; Parrilla, Pascual

    2015-12-01

    Differentiated thyroid carcinoma includes 2 different tumor types, papillary (PC) and follicular carcinoma (FC), and although similar, their prognosis is different. FC is uncommon, and this has led to it often being analyzed together with PC, and therefore the true reality of this tumor is difficult to know. As a result, the diagnostic and therapeutic management and the prognostic factors in differentiated carcinoma are more predictive of PC than FC. In this review we analyze the current state of many of the therapeutic aspects of this pathology. The best surgical technique and the usefulness of associated lymphadenectomy is also analyzed. Regarding post-surgical ablation with 131I, the indications, doses and usefulness are discussed. For the remaining therapies we analyze the few indications for radiotherapy and chemotherapy, and of new drugs such as tyrosine kinase inhibitors.

  12. Genetic heterogeneity of hepatocellular carcinoma

    SciTech Connect

    Unsal, H.; Isselbacher, K.J. ); Yakicier, C.; Marcais, C.; Ozturk, M. ); Kew, M. ); Volkmann, M. ); Zentgraf, H. )

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  13. Radioimmune localization of occult carcinoma

    SciTech Connect

    Duda, R.B.; Zimmer, A.M.; Rosen, S.T.; Gilyon, K.A.; Webber, D.; Spies, S.; Spies, W.; Merchant, B. )

    1990-07-01

    Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan results in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer.

  14. Current management of pancreatic carcinoma.

    PubMed Central

    Lillemoe, K D

    1995-01-01

    OBJECTIVE: The author seeks to provide an update on the current management of pancreatic carcinoma, including diagnosis and staging, surgical resection and adjuvant therapy for curative intent, and palliation. SUMMARY BACKGROUND DATA: During the 1960s and 1970s, the operative mortality and long-term survival after pancreaticoduodenectomy for pancreatic carcinoma was so poor that some authors advocated abandoning the procedure. Several recent series have reported a marked improvement in perioperative results with 5-year survival in excess of 20%. Significant advances also have been made in areas of preoperative evaluation and palliation for advanced disease. CONCLUSION: Although carcinoma of the pancreas remains a disease with a poor prognosis, advances in the last decade have led to improvements in the overall management of this disease. Resection for curative intent currently should be accomplished with minimal perioperative mortality. Surgical palliation also may provide the optimal management of selected patients. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 7. PMID:7531966

  15. Mucoepidermoid carcinoma of the liver.

    PubMed

    Katsuda, S; Nakanishi, I; Kajikawa, K; Takabatake, S

    1984-01-01

    An autopsy case of mucoepidermoid carcinoma of the liver associated with congenital cysts in a 78-year-old man was reported. The liver weighed 1,900 g, and there was a massive tumor of 11 X 10 X 6.5 cm in the left lobe with multiple sero-mucinous cysts. Histologically, the tumor cells consisted of four types of cells: mucus-secreting cells, squamous cells, intermediate cells, and oxyphilic cells. The variety of tumor cells quite resembled that of mucoepidermoid carcinoma of the salivary gland. The sero-mucinous cysts were lined with a single layer of cuboidal or columnar cells and were not communicated with the biliary ducts. Part of the cysts with benign lining cells was in continuity with tumor cells of the intermediate type. Discussion was made on the histogenesis of hepatic mucoepidermoid carcinoma in particular emphasis on the association of the congenital cysts.

  16. Parathyroid carcinoma in tertiary hyperparathyroidism.

    PubMed

    Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun

    2016-10-01

    Parathyroid carcinoma is a rare disease of unknown etiology. This study presents a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Despite a successful kidney transplantation, the intact parathyroid hormone (iPTH) level of the patient was elevated consistently and could not be controlled by medical therapy. Due to the development of tertiary hyperparathyroidism with bone pain and osteoporosis, subtotal parathyroidectomy was performed 4 months after the kidney transplantation. Histological evaluation revealed that one of four parathyroid lesions was a parathyroid carcinoma, while the others were diffuse hyperplasia. Postoperative laboratory studies indicated a decreased level of iPTH. A positron emission tomography-computed tomography performed 6 months after the operation revealed no evidence of local recurrence or distant metastasis. PMID:27664600

  17. Screening for hepatocellular carcinoma.

    PubMed

    Merican, I

    1996-03-01

    Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian males. In Malaysia, it is one of the ten most common cancers amongst the male population. Most of our patients with HCC present to us rather late and almost all die within 4 months of diagnosis. HCC occurs more commonly in patients with cirrhosis associated with hepatitis B and C infections. Screening for HCC can lead to early detection of small tumours (< 5 cm) that are more amenable to surgical resection, resulting in improved survival rates. The average 5-year survival rate for those who have undergone surgical resection is 68% (range, 22-73%). Better results are obtained with the smaller tumours (< 2 cm in diameter). Patients with chronic hepatitis B and C infection especially those who are > 45 years of age, who have concomitant cirrhosis or have a family history of HCC should be examined every 3-6 months with periodic serum alpha-fetoprotein (AFP) measurements and abdominal ultrasound examinations. Abdominal ultrasound is useful in the detection of small tumours. While mass screening for HCC is not cost-effective in countries of low incidence of HCC, screening of high risk groups may be justified in countries with a high endemicity of HBV infection. Screening for HCC in Japan, Taiwan and China appears to yield better results than those in the West. Nonetheless, primary prevention with mass hepatitis B vaccination and blood donor screening for anti-HCV is expected to make a much greater impact in the control of HCC in the years to come.

  18. Whole Cell-SELEX Aptamers for Highly Specific Fluorescence Molecular Imaging of Carcinomas In Vivo

    PubMed Central

    He, Xiaoxiao; Guo, Qiuping; Wang, Kemin; Ye, Xiaosheng; Tang, Jinlu

    2013-01-01

    Background Carcinomas make up the majority of cancers. Their accurate and specific diagnoses are of great significance for the improvement of patients' curability. Methodology/Principal Findings In this paper, we report an effectual example of the in vivo fluorescence molecular imaging of carcinomas with extremely high specificity based on whole cell-SELEX aptamers. Firstly, S6, an aptamer against A549 lung carcinoma cells, was adopted and labeled with Cy5 to serve as a molecular imaging probe. Flow cytometry assays revealed that Cy5-S6 could not only specifically label in vitro cultured A549 cells in buffer, but also successfully achieve the detection of ex vivo cultured target cells in serum. When applied to in vivo imaging, Cy5-S6 was demonstrated to possess high specificity in identifying A549 carcinoma through a systematic comparison investigation. Particularly, after Cy5-S6 was intravenously injected into nude mice which were simultaneously grafted with A549 lung carcinoma and Tca8113 tongue carcinoma, a much longer retention time of Cy5-S6 in A549 tumor was observed and a clear targeted cancer imaging result was presented. On this basis, to further promote the application to imaging other carcinomas, LS2 and ZY8, which are two aptamers selected by our group against Bel-7404 and SMMC-7721 liver carcinoma cells respectively, were tested in a similar way, both in vitro and in vivo. Results showed that these aptamers were even effective in differentiating liver carcinomas of different subtypes in the same body. Conclusions/Significance This work might greatly advance the application of whole cell-SELEX aptamers to carcinomas-related in vivo researches. PMID:23950940

  19. Merkel cell carcinoma and chronic arsenicism.

    PubMed

    Lien, H C; Tsai, T F; Lee, Y Y; Hsiao, C H

    1999-10-01

    Arsenic is a well-documented human carcinogen. Bowen's disease, squamous cell carcinoma, and basal cell carcinoma are the most common skin cancers found in patients exposed to arsenic over the long term. Merkel cell carcinoma has been documented in Taiwanese patients who resided in an endemic area of black foot disease, another condition found in patients with chronic arsenicism. We collected all cases of Merkel cell carcinoma diagnosed at two medical centers in Taiwan (N = 11) to find a possible association between chronic arsenicism and Merkel cell carcinoma. In our study 6 of the 11 patients were residents of the endemic areas for chronic arsenicism.

  20. Thyroid carcinoma, version 2.2014.

    PubMed

    Tuttle, R Michael; Haddad, Robert I; Ball, Douglas W; Byrd, David; Dickson, Paxton; Duh, Quan-Yang; Ehya, Hormoz; Haymart, Megan; Hoh, Carl; Hunt, Jason P; Iagaru, Andrei; Kandeel, Fouad; Kopp, Peter; Lamonica, Dominick M; Lydiatt, William M; McCaffrey, Judith; Moley, Jeffrey F; Parks, Lee; Raeburn, Christopher D; Ridge, John A; Ringel, Matthew D; Scheri, Randall P; Shah, Jatin P; Sherman, Steven I; Sturgeon, Cord; Waguespack, Steven G; Wang, Thomas N; Wirth, Lori J; Hoffmann, Karin G; Hughes, Miranda

    2014-12-01

    These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

  1. Papillary thyroid carcinoma in children and adolescents.

    PubMed

    Chung, Bo Mi; Park, Sung Hee; Kim, Soo Jin; Seo, Jae Seung; Kim, Yang Soo; Shim, Hyung Jin; Lee, Jong Beum

    2014-09-01

    Differentiated thyroid carcinoma is uncommon in children and constitutes 0.5% to 3% of all pediatric malignancies. Few studies have reported imaging findings of childhood papillary thyroid carcinomas. We report 3 cases of papillary thyroid carcinomas in children. Among the 3 patients, the youngest was a 7-year-old girl. In the current report, we describe 2 cases of classic papillary thyroid carcinoma and 1 case of pediatric diffuse sclerosing variant of papillary thyroid carcinoma. The ultrasonographic features and diagnostic procedures in these pediatric patients are similar to those in adults.

  2. [Lactobacilli and colon carcinoma--A review].

    PubMed

    Wang, Shumei; Zhang, Lanwei; Shan, Yujuan

    2015-06-01

    Epidemiological studies showed that incidence of colon carcinoma is increased in the world. There are many difficulties to inhibit colon carcinoma because the causes of inducing colon carcinoma were various and interactive each other. Previous evidence supported the balance of the colonic microflora was critical in inhibiting colon carcinoma and the protection by colonic microflora could be improved by ingesting lactobacilli. Therefore, the biological functions and anticancer effects of lactobacilli attract attention of researchers. In this review we discussed the causes of colon carcinoma; the anticancer mechanisms of lactobacilli on the basis of our own studies. Eventually, we summarized the effects of anticancer of different components and metabolic products extracted from lactobacilli.

  3. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma.

    PubMed

    Deshmukh, Mahesh; Shet, Tanuja; Bakshi, Ganesh; Desai, Sangeeta

    2011-01-01

    Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

  4. Synergistic therapeutic effects of Schiff's base cross-linked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model.

    PubMed

    Wu, Xilong; He, Chaoliang; Wu, Yundi; Chen, Xuesi

    2016-01-01

    In situ formed hydrogels based on Schiff base reaction were formulated for the co-delivery of metformin (ME) and 5-fluorouracil (5FU). The reactive aldehyde-functionalized four-arm polyethylene glycol (PFA) was synthesized by end-capping of 4-arm PEG with 4-formylbenzoic acid (FA) and used as a cross-linking agent. The injectable hydrogels are designed through the quick gelation induced by the formation of covalent bonds via Schiff-base reaction of PFA with 4-arm poly (ethylene glycol)-b-poly (L-lysine) (PPLL). This formulation eliminated the need for metal catalysts and complicated processes in the preparation of in situ-forming hydrogels. In vitro degradation and drug release studies demonstrated that both ME and 5FU were released through PFA/PPLL hydrogels in a controlled and pH-dependent manner. When incubated with mouse colon adenocarcinoma cells (C26), the ME/5FU-incorporated PFA/PPLL hydrogels had synergistic inhibitory effects on the cell cycle progression and cell proliferation in colon cancer cells. After a single subcutaneous injection of the hydrogel containing ME/5FU beside the tumors of BALB/c mice inoculated with C26 cells, the dual-drug-loaded hydrogels displayed superior therapeutic activity resulted from a combination of p53-mediated G1 arrest and apoptosis in C26 cells. Hence, the Schiff's base cross-linked hydrogels containing ME and 5FU may have potential therapeutic applications in the treatments of colon cancer. PMID:26497429

  5. Genetic Polymorphisms in SLC23A2 as Predictive Biomarkers of Severe Acute Toxicities after Treatment with a Definitive 5-Fluorouracil/Cisplatin-Based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma

    PubMed Central

    Minegaki, Tetsuya; Kuwahara, Akiko; Yamamori, Motohiro; Nakamura, Tsutomu; Okuno, Tatsuya; Miki, Ikuya; Omatsu, Hideaki; Tamura, Takao; Hirai, Midori; Azuma, Takeshi; Sakaeda, Toshiyuki; Nishiguchi, Kohshi

    2014-01-01

    Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed. Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated. Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively. Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2. PMID:24578608

  6. Feasibility and Efficacy of Single Photon Emission Computed Tomography-Based Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma 8 cm or More With Portal Vein Tumor Thrombus in Combination With Transcatheter Arterial Chemoembolization

    SciTech Connect

    Shirai, Shintaro; Sato, Morio; Suwa, Kazuhiro; Kishi, Kazushi; Shimono, Chigusa; Sonomura, Tetsuo; Kawai, Nobuyuki; Tanihata, Hirohiko; Minamiguchi, Hiroki; Nakai, Motoki

    2010-03-15

    Purpose: To assess the feasibility and efficacy of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B 3D-CRT) for large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods and Materials: HCC patients with PVTT in the first branch or main trunk, 8 cm or greater in size, were admitted to the study. SPECT, using Tc-99m-galactosyl human serum albumin, was used in radiation treatment planning to explore the optimal irradiation beam angle. SPECT enabled the minimum possible irradiation of functional liver (FL). Clinical target volume (CTV) included the main tumor and PVTT. SPECT-B 3D-CRT targeted the CTV to a total dose of 45 Gy/18 fractions. HCC outside the CTV was treated by transcatheter arterial chemoembolization (TACE). Results: Nineteen cases were enrolled in this study. The mean maximum dimension, mean CTV, and mean dose to FL were 11.0 cm (range, 8.0-20.0), 435 cm{sup 3} (range, 60-2,535), and 1,102 cGy (range, 691-1,695), respectively. Follow-up SPECT demonstrated radiation-induced dysfunctional liver. Despite the inclusion of 6 cases of Child-Pugh B or C, no patients experienced Grade 3 or worse radiation-induced liver disease. The cumulative non-progression rates of PVTT and PVTT plus main tumor were 78.0 and 43.2%, respectively. Survival rates at 1 and 2 years were 47.4 and 23.7%, respectively. Conclusions: SPECT-B 3D-CRT with TACE appears to be tolerable to cirrhotic liver and to provide promising prognosis for patients with HCC sized 8 cm or more, in comparison with previous treatment methods. A longer follow-up period is required to evaluate these findings.

  7. Xenotransplanted human prostate carcinoma (DU145) cells develop into carcinomas and cribriform carcinomas: ultrastructural aspects.

    PubMed

    Gilloteaux, Jacques; Jamison, James M; Neal, Deborah R; Summers, Jack L; Taper, Henryk S

    2012-10-01

    Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.

  8. Isolation and Characterization of Circulating Tumor Cells in Squamous Cell Carcinoma of the Lung Using a Non-EpCAM-Based Capture Method

    PubMed Central

    Bozzetti, Cecilia; Quaini, Federico; Squadrilli, Anna; Tiseo, Marcello; Frati, Caterina; Lagrasta, Costanza; Azzoni, Cinzia; Bottarelli, Lorena; Galetti, Maricla; Alama, Angela; Belletti, Silvana; Gatti, Rita; Passaro, Antonio; Gradilone, Angela; Cavazzoni, Andrea; Alfieri, Roberta; Petronini, Pier Giorgio; Bonelli, Mara; Falco, Angela; Carubbi, Cecilia; Pedrazzi, Giuseppe; Nizzoli, Rita; Naldi, Nadia; Pinto, Carmine; Ardizzoni, Andrea

    2015-01-01

    Introduction The exclusion of circulating tumor cells (CTCs) that have lost epithelial antigens during the epithelial-to-mesenchymal transition (EMT) process by using Epithelial Cell Adhesion Molecule (EpCAM) based capture methods is still a matter of debate. In this study, cells obtained after depletion procedure from blood samples of squamous cell lung cancer (SQCLC) patients were identified based on morphology and characterized with the combination of FISH assessment and immunophenotypic profile. Materials and Methods Five mL blood samples, collected from 55 advanced SQCLC patients, were analyzed by a non-EpCAM-based capture method. After depletion of leukocytes and erythroid cells, the negative fraction was characterized by both FISH using a fibroblast growth factor receptor 1 (FGFR1) probe and by immunocytochemistry. Thirty healthy donors were also tested. Results Based on morphology (nuclear dimension ≥10 μm, shape and hypercromatic aspect) suspicious circulating cells clearly distinguishable from contaminant leukocytes were observed in 49/55 (89%) SQCLC patients. Thirty-four of the 44 (77%) samples evaluable for FGFR1 FISH showed ≥ 6 FGFR1 gene copy number on average per cell. Vimentin expression involved 43% (18/42) of pooled circulating SQCLC cells, whereas only 29% (14/48) were EpCAM positive. Confocal microscopy confirmed the localization of FGFR1 probe in suspicious circulating cells. Suspicious circulating elements were also observed in healthy donors and did not show any epithelial associated antigens. A significantly lower number of suspicious circulating cells in healthy donors compared to SQCLC patients was found. Conclusions Among the heterogeneous cell population isolated by depletion procedure, the coexistence of cells with epithelial and/or mesenchymal phenotype suggests that EMT may participate to transendothelial invasion and migration of tumor cells in advanced SQCLC. The finding of cells with neither EpCAM or EMT phenotype, retrieved

  9. Synchronous triple colorectal carcinoma: a case report and review of literature

    PubMed Central

    Cheng, Ji; Liu, Xinghua; Shuai, Xiaoming; Deng, Meizhou; Gao, Jinbo; Tao, Kaixiong

    2015-01-01

    Synchronous colorectal carcinoma defines as multiple malignant lesions presented in a single patient at initial diagnosis. We report a case of triple synchronous colorectal carcinoma without related familial history. Preoperative computed tomography (CT) scan and endoscopic examination suggested multiple malignant lesions occurred in separate segments of colon. Then we performed laparoscopic total colectomy and ileorectal anastomosis with a J-type pouch. Post operative pathological examination confirmed the malignant characteristics of the triple lesions. The mini review summarizes the clinicopathological and molecular features of synchronous colorectal carcinoma based on current literatures. It appears to probably have significant distinctions with solitary tumors in terms of pathological type, primary locations and microsatellite instability. PMID:26464742

  10. Papillary Carcinoma Within a Thyroglossal Duct Cyst in a 17-Year-Old Child.

    PubMed

    Cheon, Nam Ju; Lee, Young Man; Lee, Jun Ho; Han, Jong Kyu; Lee, Ji Hye

    2016-05-01

    Thyroglossal duct cyst is a frequent event; however, papillary carcinoma within a thyroglossal duct cyst is rare, particularly in children. A 17-year-old girl presented with an asymptomatic mid-submental mass for the last 2 months. The diagnosis of thyroglossal duct cyst was made based on physical examination and computed tomography finding. After performance of Sistrunk procedure, an incidental papillary carcinoma within the thyroglossal duct cyst was observed on pathology. We reviewed the pediatric cases of thyroglossal duct carcinoma, and then decided not to perform a concurrent thyroidectomy. We will continue close follow-up for future thyroid involvement. PMID:27054418

  11. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

    PubMed

    Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

    2015-09-01

    Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

  12. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma

    PubMed Central

    Agirgol, S; Mansur, AT; Bozkurt, K; Azakli, HN; Babacan, A; Dikmen, A

    2015-01-01

    ABSTRACT Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision. PMID:26624603

  13. Mitochondriome and Cholangiocellular Carcinoma

    PubMed Central

    Bahitham, Wesam; Liao, Xiaoping; Peng, Fred; Bamforth, Fiona; Chan, Alicia; Mason, Andrew; Stone, Bradley; Stothard, Paul; Sergi, Consolato

    2014-01-01

    Cholangiocellular carcinoma (CCA) of the liver was the target of more interest, recently, due mainly to its increased incidence and possible association to new environmental factors. Somatic mitochondrial DNA (mtDNA) mutations have been found in several cancers. Some of these malignancies contain changes of mtDNA, which are not or, very rarely, found in the mtDNA databases. In terms of evolutionary genetics and oncology, these data are extremely interesting and may be considered a sign of poor fitness, which may conduct in some way to different cellular processes, including carcinogenesis. MitoChip analysis is a strong tool for investigations in experimental oncology and was carried out on three CCA cell lines (HuCCT1, Huh-28 and OZ) with different outcome in human and a Papova-immortalized normal hepatocyte cell line (THLE-3). Real time quantitative PCR, western blot analysis, transmission electron microscopy, confocal laser microscopy, and metabolic assays including L-Lactate and NAD+/NADH assays were meticulously used to identify mtDNA copy number, oxidative phosphorylation (OXPHOS) content, ultrastructural morphology, mitochondrial membrane potential (ΔΨm), and differential composition of metabolites, respectively. Among 102 mtDNA changes observed in the CCA cell lines, 28 were non-synonymous coding region alterations resulting in an amino acid change. Thirty-eight were synonymous and 30 involved ribosomal RNA (rRNA) and transfer RNA (tRNA) regions. We found three new heteroplasmic mutations in two CCA cell lines (HuCCT1 and Huh-28). Interestingly, mtDNA copy number was decreased in all three CCA cell lines, while complexes I and III were decreased with depolarization of mitochondria. L-Lactate and NAD+/NADH assays were increased in all three CCA cell lines. MtDNA alterations seem to be a common event in CCA. This is the first study using MitoChip analysis with comprehensive metabolic studies in CCA cell lines potentially creating a platform for future

  14. Spontaneous regression of hepatocellular carcinoma.

    PubMed Central

    Ayres, R C; Robertson, D A; Dewbury, K C; Millward-Sadler, G H; Smith, C L

    1990-01-01

    A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:2165992

  15. Transrectal Ultrasound of Prostatic Carcinoma

    PubMed Central

    Murray, Daniel J.; Cooperberg, Peter L.; Goldenberg, S. Larry; Toi, Ants

    1991-01-01

    The purpose of this paper is to review the indications for transrectal ultrasound; to briefly describe the sonographic technique; to describe the sonographic findings of prostatic carcinoma; to review the indications for transrectal sonographic-guided biopsy; and to discuss the controversles of routine screening and staging. ImagesFigures 1-3 PMID:21229044

  16. Genomic homogeneity in fibrolamellar carcinomas

    PubMed Central

    Sirivatanauksorn, Y; Sirivatanauksorn, V; Lemoine, N; Williamson, R; Davidson, B

    2001-01-01

    BACKGROUND—Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AP-PCR) technique to detect genetic alterations in this disease.
AIM—The aim of this study was to assess the degree of genomic heterogeneity of FLC using the AP-PCR technique.
METHODS—A total of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers.
RESULTS—DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed.
CONCLUSIONS—Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC.


Keywords: fibrolamellar carcinoma; hepatocellular carcinoma; DNA fingerprint; arbitrarily primed-polymerase chain reaction; laser capture microdissection PMID:11413114

  17. Radiotherapy T1 glottic carcinoma

    SciTech Connect

    Zablow, A.I.; Erba, P.S.; Sanfillippo, L.J.

    1989-11-01

    From 1970 to 1985, curative radiotherapy was administered to 63 patients with stage I carcinoma of the true vocal cords. Precision radiotherapeutic technique yields cure rates comparable to surgical results. Good voice quality was preserved in a high percentage of patients.

  18. Mandible metastasis of hepatocellular carcinoma.

    PubMed

    Niedzielska, Iwona; Langowska-Adamczyk, Helena; Pajak, Jacek; Kajor, Maciej; Niedzielski, Zbigniew; Gołka, Dariusz

    2004-01-01

    Metastases to oral cavity are very uncommon. We present a case of hepatocellular carcinoma (HCC) metastasis to the jaw. The x-ray examination and clinical picture of the lesion were not characteristic. The gingival metastasis may mimic other benign and malignant conditions which affect jaw and therefore the histopathological examination is necessary to make an ultimate diagnosis.

  19. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  20. Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy

    PubMed Central

    Rotoli, Deborah; Morales, Manuel; Del Carmen Maeso, María; Del Pino García, María; Morales, Araceli; Ávila, Julio; Martín-Vasallo, Pablo

    2016-01-01

    The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker. PMID:27446431

  1. Organ-preserving surgery for penile carcinoma.

    PubMed

    Martins, Francisco E; Rodrigues, Raul N; Lopes, Tomé M

    2008-01-01

    Introduction. Penile carcinoma has traditionally been treated by either surgical amputation or radical radiotherapy, both associated with devastating anatomical, functional, and psychological impact on the patient's life. Innovative surgical techniques have focused on penile preservation in well-selected patients to minimize physical disfigurement and consequently maximize quality of life. The objective of this article is to define the current status of these organ-preserving surgical options for penile carcinoma. Materials and Methods. An extensive review of the Pubmed literature was performed to find articles discussing only reconstructive surgery which have contributed significantly to change traditional, frequently mutilating treatments, to develop less disfiguring surgery, and to improve patients' quality of life over the last two decades. Results. Several articles were included in this analysis in which a major contribution to the change in therapy was thought to have occurred and was documented as beneficial. Some articles reported novel techniques of less-mutilating surgery involving different forms of glans reconstruction with the use of flaps or grafts. The issue of safe surgical margins was also addressed. Conclusion. The development of less-disfiguring techniques allowing phallus preservation has reduced the negative impact on functional and cosmetic outcomes of amputation without sacrificing oncological objectives in appropriately selected patients based on stage, grade, and location of the tumour. Until more prospective studies are available and solid evidence is documented, organ preservation should be offered with caution.

  2. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

    PubMed

    Pilotti, S; Collini, P; Mariani, L; Placucci, M; Bongarzone, I; Vigneri, P; Cipriani, S; Falcetta, F; Miceli, R; Pierotti, M A; Rilke, F

    1997-12-01

    We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

  3. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1342018

  4. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. [Basaloid Carcinoma of the Esophagus with Lugol-Voiding Lesions--A Case Report].

    PubMed

    Shimakawa, Takeshi; Asaka, Shinichi; Shimazaki, Asako; Yamaguchi, Kentaro; Usui, Takebumi; Yokomizo, Hajime; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Katsube, Takao; Naritaka, Yoshihiko; Fujibayashi, Mariko

    2015-11-01

    Patients with Lugol-voiding lesions of the esophagus are frequently affected with multiple cancers. Basaloid carcinoma of the esophagus is a very rare disease characterized by growth in the submucosal layer that exhibits a submucosal tumor-like shape. There have been some reports that this type of carcinoma is biologically high-grade. We report a case of metachronous squamous cell carcinoma in situ and superficial basaloid carcinoma in the esophagus with Lugol-voiding lesions. A 63-year-old man underwent gastrectomy for gastric cancer at the age of 45 years. The subsequent surveillance endoscopy found a type 0-Ⅱc lesion in the esophagus in 2000. EMR was thus performed. The pathology showed squamous cell carcinoma in situ. Dysplasia was diagnosed based on the Lugol-voiding lesions, and EMR was performed twice. In 2014, a fourth EMR was performed after a high-grade intraepithelial neoplasia was diagnosed. The pathology showed squamous cell carcinoma in situ and a basaloid carcinoma in the lamina propria, T1a-LPM, ly0, v0, pHMX, pVM0. The patient has had no recurrence for approximately 1 year after the fourth EMR.

  6. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    SciTech Connect

    Suhane, Sonal; Berel, Dror; Ramanujan, V. Krishnan

    2011-09-09

    Highlights: {yields} We monitored mitochondrial NDUFS3 expression in clinical breast cancer specimens. {yields} NDUFS3 expression is significantly higher in highly invasive cancer specimens. {yields} Increased NDUFS3 expression correlates with tumor nuclear grade. {yields} NDUFS3 expression in invasive ductal carcinoma is a potential hypoxia marker. -- Abstract: We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

  7. Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas.

    PubMed

    Chmelařová, M; Sirák, I; Mžik, M; Sieglová, K; Vošmiková, H; Dundr, P; Němejcová, K; Michálek, J; Vošmik, M; Palička, V; Laco, J

    2016-01-01

    Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples. We also compared the human papilloma virus (HPV) status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in RASSF1, CDH13, ESR1 and TP73 genes in the sinonasal cancer group compared with the control group. HPV positivity was found in 15/64 (23.4 %) of all samples in the carcinoma group and in no sample in the control group. No correlation was found between DNA methylation and HPV status. In conclusion, our study showed that there are significant differences in promoter methylation in the RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in these genes in carcinogenesis of the sinonasal area. These findings could be used as prognostic factors and may have implications for future individualised therapies based on epigenetic changes. PMID:27516190

  8. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    PubMed

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-04-04

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

  9. Minor salivary gland carcinoma: a review of 35 cases.

    PubMed

    Haymerle, Georg; Schneider, Sven; Harris, Luke; Häupl, Theresia; Schopper, Christian; Pammer, Johannes; Grasl, Matthaeus Ch; Erovic, Boban M

    2016-09-01

    Minor salivary gland carcinomas represent a heterogeneous group of tumors with broad variation in clinical appearance and histopathology. Clinical data of patients with small salivary gland malignancies were collected from the medical records. Tissue microarray was constructed to determine the expression pattern of 24 proteins in 35 patients with minor salivary gland carcinomas. The choice of markers was based on involvement in neoangiogenesis, cell-to-cell contact, cell-cycle regulation and carcinogenesis. Protein expression data were correlated to patients' clinical data. Overexpression of patched (p = 0.046) and Smo (p = 0.032) was linked to a better overall survival and Glutathione S-transferase π overexpression was linked to prolonged disease-free survival (p = 0.005). Cox-1 (p = 0.035) and VEGFR2 (p = 0.009) were significantly linked to decreased survival for recurrent disease. Bcl-x (84 %), β-catenin (87 %) and Cox-2 (87 %) were significantly overexpressed in minor salivary gland carcinomas. We have shown that Smo resulted in a better overall survival, whereas Gstπ in improved disease-free survival. VEGFR2 was a prognostic factor for survival after recurrence in patients with minor salivary gland carcinomas. Cyclooxygenase inhibitors and anti-Wnt-1 antibodies might be a potential therapeutic option in an adjuvant setting or for patients with unresectable tumors of the minor salivary glands.

  10. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    PubMed

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-01-01

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy. PMID:27173185

  11. Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

    PubMed

    Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

    2016-06-01

    Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. PMID:26832771

  12. Carcinoma of the gastroesophageal junction in Chinese patients

    PubMed Central

    Huang, Qin

    2012-01-01

    Carcinoma of the gastroesophageal junction (GEJ) is defined as carcinoma that crosses the GEJ line, irrespective of where the tumor epicenter is located. This group of cancer is rare but controversial. Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries, this cancer is believed to arise from Barrett’s esophagus (BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology, clinicopathology, and molecular pathobiology in relation to BE. As such, the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma (EA). This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients. The emerging evidence derived from those studies suggests: (1) both BE and EA are uncommon in the Chinese population; (2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer, not those of EA; (3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients’ prognosis effectively; and (4) prognostic factors of GEJ cancer in Chinese are similar, but not identical, to those of EA. In conclusion, the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA. Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease. PMID:23326117

  13. Carcinoma of the gastroesophageal junction in Chinese patients.

    PubMed

    Huang, Qin

    2012-12-28

    Carcinoma of the gastroesophageal junction (GEJ) is defined as carcinoma that crosses the GEJ line, irrespective of where the tumor epicenter is located. This group of cancer is rare but controversial. Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries, this cancer is believed to arise from Barrett's esophagus (BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology, clinicopathology, and molecular pathobiology in relation to BE. As such, the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma (EA). This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients. The emerging evidence derived from those studies suggests: (1) both BE and EA are uncommon in the Chinese population; (2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer, not those of EA; (3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively; and (4) prognostic factors of GEJ cancer in Chinese are similar, but not identical, to those of EA. In conclusion, the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA. Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.

  14. Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies

    PubMed Central

    Köbel, Martin; Kalloger, Steve E; Boyd, Niki; McKinney, Steven; Mehl, Erika; Palmer, Chana; Leung, Samuel; Bowen, Nathan J; Ionescu, Diana N; Rajput, Ashish; Prentice, Leah M; Miller, Dianne; Santos, Jennifer; Swenerton, Kenneth; Gilks, C. Blake; Huntsman, David

    2008-01-01

    Background Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. Methods and Findings In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1) in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%–2.4%) but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1.2%–2.3%), but

  15. Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected]. .

    PubMed

    Weigelt, Britta; Ng, Charlotte K Y; Shen, Ronglai; Popova, Tatiana; Schizas, Michail; Natrajan, Rachael; Mariani, Odette; Stern, Marc-Henri; Norton, Larry; Vincent-Salomon, Anne; Reis-Filho, Jorge S

    2015-03-01

    Metaplastic breast carcinoma is a rare and aggressive histologic type of breast cancer, preferentially displaying a triple-negative phenotype. We sought to define the transcriptomic heterogeneity of metaplastic breast cancers on the basis of current gene expression microarray-based classifiers, and to determine whether these tumors display gene copy number profiles consistent with those of BRCA1-associated breast cancers. Twenty-eight consecutive triple-negative metaplastic breast carcinomas were reviewed, and the metaplastic component present in each frozen specimen was defined (ie, spindle cell, squamous, chondroid metaplasia). RNA and DNA extracted from frozen sections with tumor cell content >60% were subjected to gene expression (Illumina HumanHT-12 v4) and copy number profiling (Affymetrix SNP 6.0), respectively. Using the best practice PAM50/claudin-low microarray-based classifier, all metaplastic breast carcinomas with spindle cell metaplasia were of cl