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Sample records for ameloblastic carcinoma based

  1. Ameloblastic Carcinoma: A Report of Three Cases

    PubMed Central

    Kodati, Sravya; Majumdar, Sumit; Namana, Madhurya

    2016-01-01

    Malignant odontogenic tumours are rare and represent approximately 1% of all oral malignancies. Ameloblastic carcinoma is a rare odontogenic tumour, which is aggressive in nature with extensive local bone destruction that has retained the features of ameloblastic differentiation and also exhibits cytological features of malignancy. It occurs primarily in the mandible in a wide range of age groups. It may arise de-novo or in pre-existing ameloblastoma or odontogenic cyst. The purpose of this report is to present three cases of ameloblastic carcinoma with varying presentations as central and peripheral entities. PMID:27891485

  2. Ameloblastic carcinoma: Report of a rare case

    PubMed Central

    Srikanth, Mandadi Dakshinamurthy; Radhika, Besta; Metta, Kiran; Renuka, Nukala Valli

    2014-01-01

    Ameloblastic carcinoma is a rare odontogenic tumor exhibiting histological evidence of malignancy in the primary or recurrent tumor. It is characterized by rapid, painful expansion of the jaw, unlike conventional ameloblastomas. The tumor most frequently involves the mandible. The expanding lesion causes perforation of the buccal and lingual plates of the jaw and invades the surrounding soft tissue. Rapidly growing large tumor mass may cause tooth mobility. A mandibular tumor involving the mental nerve leads to paresthesia of the nerve. A maxillary tumor can produce a fistula in the palate and paresthesia of the infraorbital nerve. Most ameloblastic carcinomas are presumed to have arisen de novo with a few cases of malignant transformation of ameloblastomas. Although rare, these lesions have been known to metastasize, mostly to the regional lymph nodes or lungs. A case of ameloblastic carcinoma in a 60-year-old man is reported here and its clinical, radiological and histological features are discussed. PMID:24579073

  3. Ameloblastic carcinoma of the maxillary sinus.

    PubMed

    Angiero, Francesca; Borloni, Roberto; Macchi, Maurizia; Stefani, Michele

    2008-01-01

    Ameloblastic carcinoma is a very rare malignant odontogenic neoplasm of the mandible and maxilla, accounting for some 66 reported cases. The case of a 68-year-old man who presented a fistula with orosinus communication of 14-year duration that, after anti-aggregant therapy, began bleeding is reported. The initial microscopic evaluation of the biopsy and radiographic findings were consistent with benign peripheral ameloblastoma without cellular atypia and extensive fields of acantomatous pattern, but immunohistochemical investigation found strong positivity for Bcl-2, cytokeratins CAM 5 and 6, and for Ki-67/MIB-1, changing our diagnosis. The treatment consisted of left maxillary resection followed by reconstruction. Cellular features of malignancy in the surgical specimen confirmed the diagnosis of ameloblastic carcinoma. This case of an aggressive ameloblastic carcinoma of the maxillary gingiva that presented with an unusual histological pattern illustrates that these tumors can create a diagnostic challenge that may require extensive surgical sampling and/or removal to establish the diagnosis. Immunohistochemically analyzed expression of bcl-2 protein, cytokeratins CAM 5 and 6, and Ki-67/MIB-1 antigen serve to characterize the cyto-differentiation and cellular activity of ameloblastic carcinoma.

  4. Ameloblastic carcinoma developing in preexisting ameloblastoma with a mutation of the p53 gene: a case report.

    PubMed

    Nobusawa, Aiko; Sano, Takaaki; Yokoo, Satoshi; Oyama, Tetsunari

    2014-11-01

    Ameloblastic carcinoma is a rare malignant odontogenic tumor. Here we present a case of a large ameloblastic carcinoma, which developed in a preexisting ameloblastoma in the right submandibular region. The patient was an 84-year-old woman who had received several surgical procedures for ameloblastoma, including a segmental mandibulectomy. The dimensions of the tumor were 12 × 8 × 5 cm, and both benign ameloblastoma and ameloblastic carcinoma were observed histologically. Based on histologic diagnosis, immunohistochemical staining and sequence analysis for p53 were performed. Overexpression of p53 was observed only in the ameloblastic carcinoma. Additionally, a mutation of the p53 gene (TP53) in exon 5 was found by sequence analysis in the ameloblastic carcinoma. This is the first case of ameloblastic carcinoma with a mutation of the p53 gene that has been associated with carcinomatous transformation. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Ameloblastic carcinoma of the maxilla: A case report

    PubMed Central

    FRANÇA, DIURIANNE CAROLINE CAMPOS; MOREIRA, JOÃO MILANEZ; DE AGUIAR, SANDRA MARIA HERONDINA COELHO ÁVILA; DE CARVALHOS, ARTUR ABURAD; GOIATO, MARCELO COELHO

    2012-01-01

    This study aims to present the clinical features and treatment of a case of maxillary ameloblastic carcinoma. Ameloblastic carcinoma is a rare malignant odontogenic carcinoma that has metastatic potential. Due to its rare incidence, there are few studies focusing on its radiological characteristics. When ameloblastic carcinoma demonstrates an aggressive appearance, it may be diagnosed as a malignant tumor; however, in cases showing a non-aggressive appearance, it is difficult to distinguish ameloblastic carcinoma from ameloblastoma. We report a case of ameloblastic carcinoma of the maxilla in a 59-year-old male patient, including the clinical signs, radiological images and pathological features. A partial area was surgically excised under local anesthesia and the material was sent to the Laboratory of Oral Pathology. The histological sections revealed a fragmented odontogenic tumor of epithelial origin, consisting of solid parenchyma and also revealed basal cells resembling ameloblasts, occasionally arranged in palisades. Certain parts of the architecture resembled that of an ameloblastoma; however, the cytology of other areas confirmed the diagnosis of ameloblastic carcinoma of the maxilla. The patient was scheduled for definitive surgery, including a right maxillectomy and radiotherapy. The patient was followed up every 3 months. After 2 years follow-up, there were no clinical or radiological signs of recurrence. PMID:23205126

  6. Hypermethylation of p16 tumor-suppressor gene in ameloblastic carcinoma, ameloblastoma, and dental follicles.

    PubMed

    Khojasteh, Arash; Khodayari, Abbas; Rahimi, Farzaneh; Ghaderian, Mohamad Hossain; Jafarian, Mohamad; Nayebi, Alireza; Akbarzadeh Najar, Reza; Tabatabayipanah, Akram; Jahangirnia, Alireza

    2013-01-01

    The high rate of p16 gene alterations in malignant neoplasms suggests the important effect of this tumor-suppressor gene mutation on the malignant behavior of tumoral lesions. The present study investigated the possible methylation of the p16 tumor in ameloblastic carcinoma, ameloblastoma, and dental follicles. Eighteen samples of ameloblastic carcinoma, ameloblastoma, and dental follicles of mandibular impacted third molar were selected from available documents in the archives of the Department of Oral and Maxillofacial Pathology, Taleghani Hospital and the Department of Oral and Maxillofacial Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. After confirming the initial diagnosis, 6-μm sections were used for DNA extraction. A CpG island methylation of p16 was identified by polymerase chain reaction. Although CpG methylation of p16 was observed in all ameloblastic carcinoma samples, only 1 ameloblastoma specimen exhibited the mutation. The mutation was not detected in other ameloblastoma specimens or in any dental follicle sample. The p16 alteration might play a role in the malignant progression of ameloblastic carcinoma. It is worth mentioning that ameloblastoma can be further differentiated from ameloblastic carcinoma based on molecular observations. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. Spindle cell variant of ameloblastic carcinoma: a case report and literature review.

    PubMed

    Matsushita, Yuki; Fujita, Shuichi; Yanamoto, Souichi; Yamada, Shin-ichi; Rokutanda, Satoshi; Yamashita, Kentaro; Ikeda, Tohru; Umeda, Masahiro

    2016-03-01

    Spindle cell variant of ameloblastic carcinoma is an extremely rare tumor. Severe dedifferentiated spindle cell variants are diagnostically challenging, particularly in small biopsy specimens. Here, we report a case of spindle cell variant of ameloblastic carcinoma in the mandible of a 69-year-old male patient and review the available literature. The tumor was surgically resected under general anesthesia. Histopathologic diagnosis of spindle cell carcinoma was made on incisional biopsy, and the final diagnosis was confirmed as spindle cell variant of ameloblastic carcinoma. Immunohistochemistry using cytokeratin and CK19 is helpful in determining the origin of spindle cell variant of ameloblastic carcinoma, particularly CK19 indicated that sarcomatoid spindle cells are derived from odontogenic epithelium. A review demonstrated higher mean age of patients compared with that of other types of ameloblastic carcinoma. The rates of mortality and local recurrence were concurrently 30%. No recurrence or metastasis was seen in the 23-month follow-up period in the present case.

  9. Nucleolar organizing regions and alpha-smooth muscle actin expression in a case of ameloblastic carcinoma.

    PubMed

    Kamath, Kavitha P; Vidya, M; Shetty, Nandaprasad; Karkera, Bhavana V; Jogi, Hemanth

    2010-06-01

    Ameloblastic carcinoma is a rare lesion of odontogenic origin. It is defined as a malignant epithelial odontogenic tumor that histologically has retained the features of ameloblastic differentiation and also exhibits cytologic features of malignancy, like atypia and mitotic activity. Although this lesion represents a separate entity, differentiating it from ameloblastoma has been often challenging to pathologists. In this case study reporting a case of ameloblastic carcinoma, we have attempted to verify the previous findings on the use of Argyrophilic nucleolar organizing regions (AgNORs) and immunohistochemical staining for the alpha-smooth muscle actin (alpha-SMA) in differentiating ameloblastic carcinoma from ameloblastoma. It was observed that AgNORs was found to be almost twice in ameloblastic carcinoma as it was in ameloblastoma. A difference between the two lesions in the pattern of expression of alpha-SMA was also observed, with alpha-SMA being expressed in the odontogenic epithelium and the stroma of ameloblastic carcinoma whereas, in the case of ameloblastoma, it was found only in the stromal part. These findings suggest that AgNORs and alpha-SMA expression may be used as adjuncts to the routine histopathologic examination to differentiate ameloblastic carcinoma and ameloblastoma.

  10. Nucleolar Organizing Regions and α-Smooth Muscle Actin Expression in a Case of Ameloblastic Carcinoma

    PubMed Central

    Vidya, M.; Shetty, Nandaprasad; Karkera, Bhavana V.; Jogi, Hemanth

    2010-01-01

    Ameloblastic carcinoma is a rare lesion of odontogenic origin. It is defined as a malignant epithelial odontogenic tumor that histologically has retained the features of ameloblastic differentiation and also exhibits cytologic features of malignancy, like atypia and mitotic activity. Although this lesion represents a separate entity, differentiating it from ameloblastoma has been often challenging to pathologists. In this case study reporting a case of ameloblastic carcinoma, we have attempted to verify the previous findings on the use of Argyrophilic nucleolar organizing regions (AgNORs) and immunohistochemical staining for the alpha-smooth muscle actin (alpha-SMA) in differentiating ameloblastic carcinoma from ameloblastoma. It was observed that AgNORs was found to be almost twice in ameloblastic carcinoma as it was in ameloblastoma. A difference between the two lesions in the pattern of expression of alpha-SMA was also observed, with alpha-SMA being expressed in the odontogenic epithelium and the stroma of ameloblastic carcinoma whereas, in the case of ameloblastoma, it was found only in the stromal part. These findings suggest that AgNORs and alpha-SMA expression may be used as adjuncts to the routine histopathologic examination to differentiate ameloblastic carcinoma and ameloblastoma. PMID:20333560

  11. A Rare Case Report of Spindle Cell Ameloblastic Carcinoma Involving the Mandible

    PubMed Central

    Kunche, Arunodaya; Ananthaneni, Anuradha; Bagalad, Bhavana S; Kuberappa, Puneeth Horatti

    2017-01-01

    Ameloblastic Carcinoma (AC) is uncommon malignant epithelial odontogenic tumour of jaw, with characteristic histologic features and behavior. Clinically, it has aggressive, infiltrative growth pattern with a distinct predilection for mandible. It exhibits histologic features of ameloblastoma and gets dedifferentiated overtime to culminate in carcinoma. Majority of the cases arise denovo (primary) and only few cases arise from a pre-existing ameloblastoma (secondary). Spindle-cell differentiation in ameloblastic carcinoma is rare; Salter described it as a separate entity “low-grade spindle cell ameloblastic carcinoma. Here we report a case of 32-year-old female patient who presented with a swelling present for past six months. It was diagnosed as Spindle cell Ameloblastic Carcinoma (SpAC), after the hemimandibulectomy the patient was under regular follow up for 14 months, no sign of recurrence was seen. PMID:28274070

  12. Ameloblastic carcinoma with features of ghost cell odontogenic carcinoma in a patient with suspected Gardner syndrome.

    PubMed

    Fitzpatrick, S G; Hirsch, S A; Listinsky, C M; Lyu, D J-H; Baur, D A

    2015-04-01

    Ameloblastic carcinoma and ghost cell odontogenic carcinoma are rare malignancies arising in odontogenic epithelium within the jaws. Gardner syndrome is a multifaceted autosomal dominant condition, which results in multiple dentofacial anomalies along with premalignant colon polyp formation and tumor formation in the skin and other organs. We report a case of ameloblastic carcinoma with features of ghost cell odontogenic carcinoma and extensive clear cell change and melanin pigmentation in a patient with clinical features of Gardner syndrome. To the best of our knowledge, odontogenic carcinoma arising in a patient with features of Gardner syndrome has not been reported previously. The clinical, radiographic, and histologic features of the case are discussed along with a review of the relevant literature.

  13. Immunohistochemical expression of podoplanin (D2-40), lymphangiogenesis, and neoangiogenesis in tooth germ, ameloblastomas, and ameloblastic carcinomas.

    PubMed

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

    2017-09-01

    Ameloblastoma is a benign but locally aggressive odontogenic tumor, while ameloblastic carcinoma is its malignant counterpart. Angiogenesis and lymphangiogenesis in malignancies have been correlated with higher aggressiveness and poor prognosis, as well as greater expression of podoplanin by tumoral cells. Immunohistochemical expression of podoplanin, CD34, and CD105 (endoglin) was evaluated in 53 ameloblastomas and three ameloblastic carcinomas; additionally, immunohistochemistry for podoplanin was also performed in 10 tooth germs. Microvessel density of blood and lymphatic vessels was calculated and compared between ameloblastomas and ameloblastic carcinomas. Immunoexpression of podoplanin by ameloblastic cells was evaluated in tooth germs, ameloblastomas, and ameloblastic carcinomas. Podoplanin was similarly expressed by odontogenic epithelial cells of tooth germs and ameloblastomas, while its expression was lower in ameloblastic carcinomas. There was no difference in microvessel density assessed by CD34 between ameloblastomas and ameloblastic carcinomas; nevertheless, the latter presented higher amounts of lymphatic and new formed blood vessels. Results suggest that podoplanin does not seem to be involved in invasion mechanisms of ameloblastic carcinomas, as its expression was decreased in the malignant tumoral cells. On the other hand, the increased lymphatic microvessel density and neoangiogenesis found in ameloblastic carcinomas could be related to its aggressiveness and potential for metastasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Identification of proteins with increased levels in ameloblastic carcinoma.

    PubMed

    García-Muñoz, Alejandro; Bologna-Molina, Ronell; Aldape-Barrios, Beatriz; Licéaga-Escalera, Carlos; Montoya-Pérez, Luis A; Rodríguez, Mario A

    2014-06-01

    The comparative proteomic approach by a combination of 2-dimensional electrophoresis and matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MS) analysis is an attractive strategy for the discovery of cancer biomarkers and therapeutic targets. The identification of protein biomarkers associated with ameloblastic carcinoma (AC), a malignant epithelial odontogenic tumor, will potentially improve the diagnostic and prognostic accuracy for this malignant neoplasm. The aim of the present study was to identify highly expressed proteins in AC that could be considered as potential biomarkers. The protein profile of an AC was compared with the protein profiles of 3 cases of benign ameloblastoma. Proteins that showed increased levels in AC were identified using MS, and the augmented amount of some of these proteins in the malignant lesion was confirmed by Western blot or immunohistochemistry. We detected a total of 782 spots in the protein profile of AC, and 19 of them, showing elevated levels compared with benign ameloblastoma, were identified using MS. These proteins have been implicated in several cellular functions, such as cell structure, metabolism, stress response, and signal transduction. The increased expression of the identified proteins and the minor expression of some proteins that might inhibit tumor progression could be involved in the evolution from a benign lesion to carcinoma. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Alpha Smooth Muscle Actin Expression in a Case of Ameloblastic Carcinoma: a Case Report

    PubMed Central

    Garg, Vipul

    2013-01-01

    ABSTRACT Background The aim of the present article is to report a case of ameloblastic carcinoma and use a marker alpha smooth muscle actin as a tool to differentiate cases of ameloblastic carcinoma from that of ameloblastoma. Methods Case study reporting a case of ameloblastic carcinoma (AC) with expression of alpha smooth muscle actin (alpha-SMA) as a marker for emergence of stromal myofibroblasts. The expression of myofibroblasts was also compared with that of ameloblastoma. Results Difference between the two lesions in the pattern of expression of alpha smooth muscle actin was also observed. There was increase in the number of myofibroblasts in the stroma of AC while in ameloblastoma, it was comparatively less. Secondly, few areas of the carcinomatous ameloblastic island also exhibited a mild positivity towards alpha smooth muscle actin. Conclusions Increase in number of stromal myofibroblast may be taken as a predictor for carcinomatous transformation. Further studies with greater sample size can validate the use of alpha-SMA as a marker to differentiate ameloblastic carcinoma from ameloblastoma. PMID:24422027

  16. Ameloblastic carcinoma of the mandible: Report of a case and review

    PubMed Central

    Kallianpur, Shreenivas; Jadwani, Sanjay; Misra, Biswajit; Sudheendra, U S

    2014-01-01

    Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that can arise either as a de novo lesion or from pre-existing ameloblastoma. Histopathologically, the tumor retains an ameloblastomatous differentiation pattern but shows cytological features of malignancy. Owing to variable biologic behavior and paucity of long-term follow-up cases, there has been no clear consensus on treatment protocol. The present case of ameloblastic carcinoma arose in the mandible of a 24-year-old male. Surgical treatment involved resection of the mandible along with regional lymph nodes. The patient has been on follow up for the past one year without any recurrence or metastases. An update on ameloblastic carcinoma encompassing the histogenesis, immunohistochemical features and treatment aspects are included. PMID:25364189

  17. Primary ameloblastic carcinoma of the maxilla: A case report and literature review

    PubMed Central

    UZAWA, NARIKAZU; SUZUKI, MIHO; MIURA, CHIKA; TOMOMATSU, NOBUYOSHI; IZUMO, TOSHIYUKI; HARADA, KIYOSHI

    2015-01-01

    Ameloblastic carcinoma (AC) is a rare malignant odontogenic neoplasm that tends to occur in the mandible rather than in the maxilla. This malignancy is classified as a tumor that combines the morphological features of ameloblastoma and carcinoma, regardless of the presence or absence of metastasis. In addition, AC has been classified into two types, primary and secondary. The former develops de novo and the latter develops by malignant transformation of a pre-existing benign ameloblastoma. The present study describes the case of a 22-year-old patient with primary AC of the maxilla. A review of the literature focusing on the clinical details, treatment results and histopathological and phenotypic information available for ameloblastic carcinoma of the maxilla from a 60-year period was also performed. As a result, it was found that primary AC is dominant in the maxilla and does not exhibit an aggressive phenotype compared with secondary AC. In addition, the presence of recurrence was found to correlate with mortality, indicating that early, aggressive and complete removal of the tumor is the best treatment for survival. PMID:25436009

  18. 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. © The Author(s) 2016.

  19. Low-grade spindle-cell ameloblastic carcinoma: report of an unusual case with immunohistochemical findings and review of the literature

    PubMed Central

    Jindal, C.; Palaskar, S.; Kaur, H.; Shankari, M.

    2010-01-01

    Spindle-cell differentiation in ameloblastic carcinoma is a rare event. Although reported by many authors, it was first described as a separate entity in 1999 by Slater under the heading “low-grade spindle-cell ameloblastic carcinoma.” Here, we report a case of low-grade spindle-cell ameloblastic carcinoma arising in pre-existing unicystic ameloblastoma. The patient, a 60-year-old Indian woman, had a large irregular swelling in the left mandibular region. Histologically, the lesion was composed of a large cystic cavity with an ameloblastomatous lining and areas showing spindle-cell proliferation. The spindle cells showed hyperchromatism, nuclear pleomorphism, and scattered mitotic figures. To our knowledge, 6 cases of spindle-cell ameloblastic carcinoma have been published to date, and this case appears to be the first reporting malignant transformation with spindle-cell differentiation in unicystic ameloblastoma. PMID:20975879

  20. Ameloblastic carcinoma of the maxilla: A case report and an updated review of the literature

    PubMed Central

    Moro, Alessandro; Foresta, Enrico; Gasparini, Giulio; Pelo, Sandro; Forcione, Mario; Cristallini, Enrico Giuseppe; Toraldo, Marco; Lorenzo, Cardarelli; Falchi, Marco; Saponaro, Gianmarco

    2016-01-01

    Ameloblastic carcinoma (AC) is an uncommon malignant odontogenic tumor that can be difficult to differentiate from ameloblastoma and can arise directly as an undifferentiated lesion or from a pre-existing benign lesion. The current study presents a novel case of primary maxillary AC and review the literature on AC of the maxilla. The review of the literature indicates that secondary tumors and posterior localization are associated with a higher tendency for recurrence and, often, multiple recurrences. Surgical therapy, eventually followed by radiotherapy, is the treatment modality most frequently applied, while the role of chemotherapy remains unclear. Several new cases of maxillary AC have been recently described in literature, making this pathology more frequent than previously considered; this is perhaps an indication of an increased diagnostic sensibility, rather than a real increase in the incidence of the disease itself. PMID:28105148

  1. Ameloblastic fibrosarcoma involving the anterior and middle skull base with intradural extension.

    PubMed

    Guthikonda, Bharat; Hanna, Ehab Y; Skoracki, Roman J; Prabhu, Sujit S

    2009-11-01

    Ameloblastic fibrosarcoma is a malignant odontogenic tumor that rarely affects the skull base and surrounding regions. We present a case of a 48-year-old man with histologically confirmed malignant transformation of a benign ameloblastic fibroma 10 years after initial presentation of a localized facial mass. The ameloblastic fibrosarcoma extended from the facial region to the orbit, anterior and middle fossa skull base, the infratemporal fossa, and the cavernous sinus. Progressive proptosis with complete monocular vision loss was the presenting symptom. To our review, our case represents the first report of intradural extension of ameloblastic fibrosarcoma. Using a multidisciplinary skull base approach, resection of all tumors except that in the cavernous sinus was achieved with the resulting defect reconstructed with an anterolateral thigh free flap. The patient had no new neurologic deficits after surgery and underwent adjuvant fractionated radiation therapy. Malignant transformation of ameloblastic fibroma into ameloblastic fibrosarcoma can occur many years after initial presentation. Thus, vigilant long-term follow-up is essential despite the benign nature of the initial pathologic lesion. Use of a multidisciplinary approach is critical in obtaining the optimal outcome in these complex cases.

  2. The variability and complexity of ameloblastoma: carcinoma ex ameloblastoma or primary ameloblastic carcinoma.

    PubMed

    Lin, Zitong; Chen, Fei; Wang, Tiemei; Hu, Qingang; Sun, Guowen

    2013-04-01

    Ameloblastoma is characterized by slow-growing, local invasiveness and high incidence of local recurrence. It usually presents with a benign histological appearance. However, ameloblastoma occasionally demonstrates a clinical course that is characteristic of malignant transformation. Here, we present a case of ameloblastoma with an aggressive clinical course, including multiple recurrences, a short disease-free interval, pulmonary metastasis and extensive skull-base infiltration. With a careful re-evaluation of the histology and cytology of the specimens of primary and recurrent ameloblastoma in 2006 and 2007, malignant transformation was observed and carcinoma ex ameloblastoma was ultimately diagnosed. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  3. Ameloblastic carcinoma of the mandible with metastasis to the skull and lung: advanced imaging appearance including computed tomography, magnetic resonance imaging and positron emission tomography computed tomography

    PubMed Central

    Devenney-Cakir, B; Dunfee, B; Subramaniam, R; Sundararajan, D; Mehra, P; Spiegel, J; Sakai, O

    2010-01-01

    Ameloblastic carcinoma is a very rare malignant odontogenic tumour with characteristic histopathological and clinical features, which requires aggressive surgical treatment and surveillance and, therefore, differs from ameloblastoma. Metastasis typically occurs in the lung. Only one patient with metastasis to the skull has previously been described and no prior case reports have presented MRI and positron emission tomography-CT (PET-CT) imaging findings. We describe a case of ameloblastic carcinoma with metastasis to the skull and lung with emphasis on imaging features including MRI and PET-CT. PMID:20841465

  4. Ameloblastic fibroma

    PubMed Central

    Rao, Srinivas Ponnam; Srivastava, Gautam; Smitha, B

    2012-01-01

    Ameloblastic fibroma is a rare odontogenic tumor comprising neoplastic epithelial and mesenchymal tissues. This lesion was previously considered to be a benign lesion with very limited recurrence rate and malignant transformation. However, recent reports have suggested that this lesion has the potential for recurrence and malignant transformation. In this brief report, we report a case of AF in the context of its high cellularity on histopathological examination. PMID:23248485

  5. Ameloblastic fibroma.

    PubMed

    Rao, Srinivas Ponnam; Srivastava, Gautam; Smitha, B

    2012-09-01

    Ameloblastic fibroma is a rare odontogenic tumor comprising neoplastic epithelial and mesenchymal tissues. This lesion was previously considered to be a benign lesion with very limited recurrence rate and malignant transformation. However, recent reports have suggested that this lesion has the potential for recurrence and malignant transformation. In this brief report, we report a case of AF in the context of its high cellularity on histopathological examination.

  6. Ameloblastic fibro odontoma.

    PubMed

    Sivapathasundharam, B; Manikandhan, R; Sivakumar, G; George, Titus

    2005-01-01

    Ameloblastic fibro odontoma is relatively a rare mixed odontogenic tumor comprising of ameloblastic fibroma and ameloblastic odontoma. This group of lesions represent neoplastic and hamartomatous changes. Data regarding age, sex, and site of occurrence of these lesions have been uniquely described. A case of ameloblastic fibro odontoma in a 17-year-old male involving the left body of the mandible, and its radiographic, clinical symptoms and histological features is described herewith. A conservative surgical approach, including enucleation and mechanical curettage of the surrounding bone was done.

  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.

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

    PubMed Central

    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

  9. Peripheral ameloblastic fibroma.

    PubMed

    Darling, M R; Daley, T D

    2006-03-01

    Peripheral ameloblastic fibroma is an exceedingly rare lesion. Only three reports could be found, two of which appeared in the Japanese literature. Here, we report a case of peripheral ameloblastic fibroma occurring in a 5-year-old girl. The diagnosis was made after careful microscopic examination, to exclude other lesions. The lesion was excised and has not recurred 1 year after removal.

  10. Ameloblastic fibrosarcoma: a rare malignant odontogenic tumor.

    PubMed

    Gilani, S M; Raza, A; Al-Khafaji, B M

    2014-02-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor. It can arise de novo, however one-third of cases may arise from a recurrent ameloblastic fibroma, in which case they appear to present at an older age. A 16-year-old female presented with one month history of right mandibular mass. Computerized tomography (CT) scan showed a large destructive mass. A biopsy of the mass was performed. Histologically, it consisted of a mixed epithelial-mesenchymal odontogenic neoplasm composed of benign islands of well-differentiated ameloblastic epithelium within a malignant fibrous stroma consisting of spindle cells or fibroblasts with a brisk mitotic activity. The malignant spindle cell proliferation showed positive staining with p-53 and a high proliferation index with ki-67. A diagnosis of AFS was rendered. The differential diagnosis includes other odontogenic sarcomas, ameloblastic carcinosarcoma and spindle cell carcinoma. Treatment of choice is wide surgical excision, with long-term follow-up. Postoperative chemotherapy and radiotherapy has been used successfully in a few reported cases. AFS is a locally aggressive malignant tumor, with regional and distant metastases being uncommon. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Malignant transformation of ameloblastic fibro-odontoma to ameloblastic fibrosarcoma.

    PubMed

    Howell, R M; Burkes, E J

    1977-03-01

    Two cases of malignant transformation of ameloblastic fibro-odontomas are presented, along with a review of the literature on ameloblastic fibrosarcomas. The occurrence of this malignant transformation of ameloblastic fibromas, ameloblastic odontomas, and ameloblastic fibro-odontomas appears to be more frequent than previously thought. This potential transformation alone does not justify radical treatment of all these benign lesions. If there is recurrence accompanied by a histologic pattern change toward a more unorganized fibrous stroma with displacement of the epithelial component, however, then more extensive treatment procedures appear to be indicated.

  12. Ameloblastic fibrosarcoma: a cytologist's perspective.

    PubMed

    Gupta, Nalini; Barwad, Adarsh; Kumar, Rajiv; Rijuneeta; Vaiphei, Kim

    2011-08-01

    Fine-needle aspiration cytology of a case of ameloblastic fibrosarcoma (AFS), an unusual odontogenic tumor related to ameloblastoma (AB), was performed in a 25-year-old female with a 1 cm swelling in the left lower orbital region along with involvement of zygomatic region. Aspiration of the tumor yielded a cellular sample composed predominantly of mesenchymal element and few clusters representing epithelial component showing tall columnar cells with peripheral palisading. Detailed cytomorphological features of AFS are discussed along with differential diagnosis from other tumors such as AB, desmoplastic AB, odontogenic fibroma, ameloblastic fibrodentinoma and ameloblastic fibro-odontoma, ameloblastic fibroma. Copyright © 2010 Wiley-Liss, Inc.

  13. 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).

  14. Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

    PubMed Central

    Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

    2013-01-01

    Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

  15. 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.

  16. Aspiration cytology of ameloblastic fibroma: a diagnostic challenge.

    PubMed

    Kumar, Neeta; Jain, Shyama

    2003-08-01

    Ameloblastic fibroma of the jaw is a rare, benign mixed odontogenic tumor, having little tendency for local invasion and a low recurrence rate. Cytologic distinction from ameloblastoma, ameloblastic fibrosarcoma, and intraosseous adenoid cystic carcinoma is necessary, in view of the different biologic behavior. A painful, slow-growing swelling of the jaw in a 5-yr-old child clinicoradiologically considered as a benign cystic lesion was aspirated. Sheets of small monomorphic epithelial cells with peripheral palisading by columnar cells were seen on cytology smears. The striking feature was central hyaline globules in some tubules. A cytologic possibility of adenomatoid odontogenic tumor was suggested. Histopathology, however, confirmed it to be an ameloblastic fibroma. Copyright 2003 Wiley-Liss, Inc.

  17. Giant ameloblastic fibroma.

    PubMed

    Büyükakyüz, N; Ergun, S; Soluk, M; Uyumaz, N; Tanyeri, H

    2009-03-01

    A 10 year-old male was referred to our department for a delay in the eruption of his lower canine, premolars and molars on the right side. The panoramic radiograph showed a multilocular radiolucent lesion approximately 3.5 x 7.5 cm in diameter including the right canine, first and second premolar and second mandibular molar. The lesion was clinically diagnosed as dentigerous cyst. It was enucleated via curettage of the bone bed and diagnosed as ameloblastic fibroma at the histopathological examination. After twenty-one months, radiographs showed that the surgical defect had filled with new bone.

  18. 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

  19. 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

  20. Ameloblastic fibro-odontoma

    PubMed Central

    Surej Kumar, L.K.; Manuel, Suvy; Khalam, Sherin A.; Venugopal, Kannan; Sivakumar, T.T.; Issac, Jyothi

    2014-01-01

    INTRODUCTION Ameloblastic fibro-odontoma (AFO) is a quite rare, mixed odontogenic tumour generally seen in the early stages of life. Frequent signs of this tumour are asymptomatic swelling, delayed tooth eruption and mixed radiological appearance within well-defined borders. Management of the lesion includes enucleation of the tumour and long-term follow-up. PRESENTATION OF CASE A 10-year-old girl was referred to our oral and maxillofacial surgery clinic with an incidental radiological finding of radiopaque mass in the posterior region of maxilla. OPG showed unerupted tooth bud of upper right second molar and was being prevented from eruption by the odontome. Under general anaesthesia, the lesion was enucleated and the permanent right upper second molar tooth bud removed. DISCUSSION Mixed odontogenic tumours are a group of rare and interesting lesions which can mislead the clinician to variety of differential diagnosis. Adequate clinical and radiological investigations, proper surgical excison, accurate histopathological diagnosis, and long term follow up will ensure the right treatment plan for the patient. CONCLUSION The possibility of a mixed rare tumour should be kept in mind by the clinician where they deal with the swellings of posterior maxilla in children. Histological assessment revealed a final diagnosis of ameloblastic fibro-odontoma. PMID:25437658

  1. Ameloblastic fibro-odontoma

    PubMed Central

    Gantala, Ramlal; Gotoor, Srikanth Goud; Kumar, R Vijaya; Munisekhar, MS

    2015-01-01

    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. PMID:26045519

  2. [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.

  3. Spontaneous Ameloblastic Fibroma in a Young Guinea Pig

    PubMed Central

    Tanaka, Makoto; Sawamoto, Osamu

    2013-01-01

    A spontaneous ameloblastic fibroma was found in a 9-week-old guinea pig. Histopathologically, neoplastic cells consisted of two components: an odontogenic epithelium and odontogenic mesenchyme. The odontogenic epithelium formed strands, nests and islands that were interspersed within the odontogenic mesenchyme. In the marginal region, odontoblasts and scant dysplastic eosinophilic material were seen between these two components. Immunohistochemically, the odontogenic epithelium was positive for cytokeratin AE1/AE3, and the odontogenic mesenchyme and odontoblast were positive for vimentin, in the same manner as in the normal tooth germ (control). We could not obtain conclusive data suggesting that the eosinophilic material was dental hard tissue because the eosinophilic material was not stained specifically by any methods. Based on these histological characteristics, the tumor in the present case was diagnosed as an ameloblastic fibroma. This is the first report of ameloblastic fibroma in guinea pigs. PMID:24155567

  4. A histopathological and immunohistochemical analysis of ameloblastic fibrodentinoma.

    PubMed

    Bologna-Molina, Ronell; Salazar-Rodríguez, Sirced; Bedoya-Borella, Ana María; Carreón-Burciaga, Ramón Gil; Tapia-Repetto, Gabriel; Molina-Frechero, Nelly

    2013-01-01

    Ameloblastic fibrodentinoma (AFD) is considered a mixed odontogenic tumor that is characterized by conserved epithelial and ectomesenchymal neoplastic components. AFD is composed of long narrow cords and islands of odontogenic epithelium; the epithelial strands lie in a myxoid cell-rich ectomesenchymal tissue with stellate-shaped fibroblasts that exhibit long slender cytoplasmic extensions that resemble dental papilla. The lesions show the presence of dysplastic dentin. Although AFD is a rare entity and its very existence is not completely accepted, based on the extent of histodifferentiation, it is considered to represent a stage between ameloblastic fibroma and ameloblastic fibroodontoma. This study aimed to provide a histopathological and immunohistochemical characterization of this infrequent tumor. A large panel of antibodies including amelogenin, Ck 19, calretinin, syndecan-1, E-cadherin, MSH2, histone H3, and Ki-67 was used to illustrate the nature of the tumor.

  5. Spontaneous ameloblastic fibroma in a young Guinea pig.

    PubMed

    Tanaka, Makoto; Sawamoto, Osamu

    2013-09-01

    A spontaneous ameloblastic fibroma was found in a 9-week-old guinea pig. Histopathologically, neoplastic cells consisted of two components: an odontogenic epithelium and odontogenic mesenchyme. The odontogenic epithelium formed strands, nests and islands that were interspersed within the odontogenic mesenchyme. In the marginal region, odontoblasts and scant dysplastic eosinophilic material were seen between these two components. Immunohistochemically, the odontogenic epithelium was positive for cytokeratin AE1/AE3, and the odontogenic mesenchyme and odontoblast were positive for vimentin, in the same manner as in the normal tooth germ (control). We could not obtain conclusive data suggesting that the eosinophilic material was dental hard tissue because the eosinophilic material was not stained specifically by any methods. Based on these histological characteristics, the tumor in the present case was diagnosed as an ameloblastic fibroma. This is the first report of ameloblastic fibroma in guinea pigs.

  6. A Histopathological and Immunohistochemical Analysis of Ameloblastic Fibrodentinoma

    PubMed Central

    Bologna-Molina, Ronell; Salazar-Rodríguez, Sirced; Bedoya-Borella, Ana María; Carreón-Burciaga, Ramón Gil; Tapia-Repetto, Gabriel; Molina-Frechero, Nelly

    2013-01-01

    Ameloblastic fibrodentinoma (AFD) is considered a mixed odontogenic tumor that is characterized by conserved epithelial and ectomesenchymal neoplastic components. AFD is composed of long narrow cords and islands of odontogenic epithelium; the epithelial strands lie in a myxoid cell-rich ectomesenchymal tissue with stellate-shaped fibroblasts that exhibit long slender cytoplasmic extensions that resemble dental papilla. The lesions show the presence of dysplastic dentin. Although AFD is a rare entity and its very existence is not completely accepted, based on the extent of histodifferentiation, it is considered to represent a stage between ameloblastic fibroma and ameloblastic fibroodontoma. This study aimed to provide a histopathological and immunohistochemical characterization of this infrequent tumor. A large panel of antibodies including amelogenin, Ck 19, calretinin, syndecan-1, E-cadherin, MSH2, histone H3, and Ki-67 was used to illustrate the nature of the tumor. PMID:23476862

  7. 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.

  8. Ameloblastic fibroma: an uncommon entity

    PubMed Central

    Vij, Ruchieka; Vij, Hitesh

    2013-01-01

    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. PMID:23843410

  9. Malignant transformation of ameloblastic fibroma to ameloblastic fibrosarcoma: case report and review of the literature.

    PubMed

    Kobayashi, Kazuo; Murakami, Ryuichi; Fujii, Tohru; Hirano, Akiyoshi

    2005-10-01

    Ameloblastic fibrosarcoma is a rare malignant odontogenic tumour and is regarded as the malignant counterpart of the ameloblastic fibroma. The epithelial component remains benign, but the mesenchymal component becomes malignant. The diagnosis is made by histopathology. The case of a 26-year-old man who underwent curettage of an ameloblastic fibroma and died of an ameloblastic fibrosarcoma is presented, and the course of malignant transformation is analysed retrospectively. One-third of ameloblastic fibrosarcoma cases seem to have developed from recurrent ameloblastic fibromas. Knowledge of the malignant potential in the mesenchymal spindle cells of ameloblastic fibroma will assist in determining the management of these benign tumours, and may prevent malignant transformation to ameloblastic fibrosarcoma.

  10. Ion Transport by Ameloblasts during Amelogenesis.

    PubMed

    Bronckers, A L J J

    2017-03-01

    Hypomineralization of developing enamel is associated with changes in ameloblast modulation during the maturation stage. Modulation (or pH cycling) involves the cyclic transformation of ruffle-ended (RE) ameloblasts facing slightly acidic enamel into smooth-ended (SE) ameloblasts near pH-neutral enamel. The mechanism of ameloblast modulation is not clear. Failure of ameloblasts of Cftr-null and anion exchanger 2 ( Ae2)-null mice to transport Cl(-) into enamel acidifies enamel, prevents modulation, and reduces mineralization. It suggests that pH regulation is critical for modulation and for completion of enamel mineralization. This report presents a review of the major types of transmembrane molecules that ameloblasts express to transport calcium to form crystals and bicarbonates to regulate pH. The type of transporter depends on the developmental stage. Modulation is proposed to be driven by the pH of enamel fluid and the compositional and/or physicochemical changes that result from increased acidity, which may turn RE ameloblasts into SE mode. Amelogenins delay outgrowth of crystals and keep the intercrystalline space open for diffusion of mineral ions into complete depth of enamel. Modulation enables stepwise removal of amelogenins from the crystal surface, their degradation, and removal from the enamel. Removal of matrix allows slow expansion of crystals. Modulation also reduces the stress that ameloblasts experience when exposed to high acid levels generated by mineral formation or by increased intracellular Ca(2+). By cyclically interrupting Ca(2+) transport by RE ameloblasts and their transformation into SE ameloblasts, proton production ceases shortly and enables the ameloblasts to recover. Modulation also improves enamel crystal quality by selectively dissolving immature Ca(2+)-poor crystals, removing impurities as Mg(2+) and carbonates, and recrystallizing into more acid-resistant crystals.

  11. Ameloblastic fibroma and ameloblastic fibrosarcoma: A systematic review.

    PubMed

    Chrcanovic, Bruno Ramos; Brennan, Peter A; Rahimi, Siavash; Gomez, Ricardo Santiago

    2017-08-04

    To integrate the available data published to date on ameloblastic fibromas (AF) and ameloblastic fibrosarcomas (AFS) into a comprehensive analysis of their clinical/radiological features. An electronic search was undertaken in July 2017. Eligibility criteria included publications having enough clinical, radiological and histological information to confirm a definite diagnosis. A total of 244 publications (279 central AF tumours, 10 peripheral AF, 103 AFS) were included. AF and AFS differed significantly with regard to the occurrence of patients' mean age, bone expansion, cortical bone perforation and lesion size. Recurrence rates were as follows: central AF (19.2%), peripheral AF (12.5%), AFS (all lesions, 35%), primary (de novo) AFS (28.8%) and secondary AFS (occurring after an AF, 50%). Larger lesions and older patients were more often treated by surgical resections for central AF. Segmental resection resulted in the lowest rate of recurrence for most of the lesion types. AFS treated by segmental resection had a 70.5% lower probability to recur (OR 0.295; P = .049) than marginal resection; 21.3% of the AFS patients died due to complications related to the lesion. Very long follow-up is recommended for AF lesions, due to the risk of recurrence and malignant change into AFS. Segmental resection is the most recommended therapy for AFS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. A Large Ameloblastic Fibro-odontoma of the Maxillary Sinus

    PubMed Central

    Banihashem Rad, Seyed Ali; Mortazavi, Hamed; Eshghpour, Majid; Salehinejad, Jahanshah; Shahakbari, Reza

    2014-01-01

    Introduction: Ameloblastic fibro-odontoma is a rare, benign, asymptomatic tumor. The term ameloblastic fibro-odontoma was first used by Hooker in 1967 as a separate lesion from ameloblastic odontoma. Case Report: This case report describes an eleven years old female with large ameloblastic fibro-odontoma in the right maxillary sinus. Conclusion: There is a low potential for recurrence after complete Enucleation of ameloblastic fibro-odontoma, but due to the risk of ameloblastic sarcoma after recurrence, the surgery should be perfect along with a careful follow up. PMID:24745000

  13. Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts.

    PubMed

    Zhang, Ying; Zhang, KaiQiang; Ma, Lin; Gu, HeFeng; Li, Jian; Lei, Shuang

    2016-09-01

    The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. High fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. These results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Expression of DCC in differentiating ameloblasts from developing tooth germs in rats.

    PubMed

    Kim, H J; Jeon, S K; Kang, J H; Kim, M S; Ko, H M; Jung, J Y; Koh, J T; Kim, W J; Lee, E J; Lim, H P; Kim, S H

    2009-06-01

    This study examined the expression pattern of the Deleted-in-colorectal-carcinoma (DCC) gene in developing rat tooth germs. Rat pups at 4, 7 and 10 d postpartum were used in this study. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescent localization were used to determine the level of DCC expression during tooth development. There was more than 2-fold higher level of DCC mRNA in the rat 2nd maxillary molar tooth germs on 10 d postpartum, which was the root stage, than in the rat 3rd maxillary molar tooth germ, which was at the cap/early bell development stage. In addition, the levels of DCC mRNA in the 2nd maxillary molar germs at 4, 7 and 10 d postpartum increased gradually according to tooth development. Interestingly, immunoreactivity against DCC was specifically detected in the differentiating ameloblasts. DCC was observed in the lateral and apical sides of the newly differentiating and secretory stage ameloblasts. Afterwards, DCC was localized only in the apical side of the maturation stage ameloblasts, not in the lateral side. DCC is expressed in the differentiating ameloblasts, which suggests that this molecule plays a crucial role in amelogenesis.

  15. Skin epithelial cells as possible substitutes for ameloblasts during tooth regeneration.

    PubMed

    Liu, Yihan; Jiang, Ming; Hao, Wei; Liu, Wenjia; Tang, Liang; Liu, Hongchen; Jin, Yan

    2013-12-01

    The disappearance of ameloblasts in erupted teeth hampers the implementation of tissue engineering-based tooth regeneration. We aimed at utilizing skin epithelial cells as the appropriate substitute for ameloblasts. The conversion potential of 1 day postnatal rat skin epithelial cells to ameloblasts was investigated under the induction of dental papillae mesenchymal cells (DPMCs). Induction strategies had been designed both in vitro and in vivo. Markers for ameloblasts had been detected in skin epithelial cells, which showed a columnar appearance with the nuclei located at one side, under indirect co-culture with DPMCs in vitro. An enamel-dentine-like and tooth germ-like structure was formed by recombining skin epithelial pieces or cells with DPMCs after 14 days of implantation in rat renal capsule. Immunohistochemistry and cell labelling analysis further demonstrated that the enamel-forming cells were skin epithelium-derived. These results indicated that the skin epithelium-derived cells from postnatal rats have the potential to convert to functional ameloblasts under effective induction. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Ameloblastic fibro-odontosarcoma: a case report.

    PubMed

    Mainenti, P; Oliveira, G S; Valério, J B; Daroda, L S L; Daroda, R F; Brandão, G; Rosa, L E B

    2009-03-01

    This paper reports one case, of an ameloblastic fibro-odontosarcoma (AFOS) affecting the mandible, in a 12-year-old girl. This neoplasm is a rare odontogenic neoplasm. To the authors' knowledge this is the fifteenth case of AFOS reported in English. The patient's chief complaint was a swelling in the face for 6 months. An incisional biopsy was performed diagnosing the case as an ameloblastic fibroma. After radiography ameloblastic fibro-odontoma was diagnosed. Computed tomography was performed and a stereolithography model made to plan the surgical procedures. A hemimandibulectomy followed by a vascularized fibular flap was then proposed. The surgery was uneventful. Microscopic features diagnosed an AFOS. After 23 months of close follow-up there is no sign of recurrence or metastasis. Dental implants were recently placed in the fibular flap.

  17. Ameloblastic fibro-odontoma: a case report

    PubMed Central

    Mummolo, Stefano; Marchetti, Enrico; Di Martino, Salvatore; Scorzetti, Luisa; Marzo, Giuseppe

    2010-01-01

    Summary The clinical case of an unusual ameloblastic fibro-odontoma (AFO) was reported. The patient’s clinical chart as well as preoperative and postoperative radiographs and histological findings of a 20-year old man that addressed Dental Clinic at University of L’Aquila were thoroughly reviewed. The patient showed a swelling in the oral cavity and radiographic feature of a radiolucent lesion at left second premolar maxillary site. Histologic examination made diagnosis of AFO. AFO is a rare mixed odontogenic tumor with similarities to the ameloblastic fibroma (AF) and ameloblastic dentinoma. The nature and the relationships between mixed odontogenic tumours and related lesions are still controversial. Moreover is not clear if these lesions are separate pathologies or if they are different development stages of the same pathology. PMID:22238705

  18. Ameloblastic fibro-odontoma: a case report.

    PubMed

    Mummolo, Stefano; Marchetti, Enrico; Di Martino, Salvatore; Scorzetti, Luisa; Marzo, Giuseppe

    2010-04-01

    The clinical case of an unusual ameloblastic fibro-odontoma (AFO) was reported. The patient's clinical chart as well as preoperative and postoperative radiographs and histological findings of a 20-year old man that addressed Dental Clinic at University of L'Aquila were thoroughly reviewed. The patient showed a swelling in the oral cavity and radiographic feature of a radiolucent lesion at left second premolar maxillary site. Histologic examination made diagnosis of AFO. AFO is a rare mixed odontogenic tumor with similarities to the ameloblastic fibroma (AF) and ameloblastic dentinoma. The nature and the relationships between mixed odontogenic tumours and related lesions are still controversial. Moreover is not clear if these lesions are separate pathologies or if they are different development stages of the same pathology.

  19. [Surgical tactics by various ameloblastic tumors].

    PubMed

    Semkin, V A; Grigor'ian, A S; Babichenko, I I; Usachev, E S; Zaretskaia, A S

    2012-01-01

    Ameloblastoma and ameloblastic fibroma are benign odontogenous tumors of the jaws with local destructive growth, prone to recurrence. They have various typical radiological and histological features. Surgical tactic generally includes partial resection of the affected jaw. Immunohistochemical study of the tumor tissues allows assessing the expression of tumor progression markers and forecasting tumor growth thus providing individual choice of surgical tactics. Our experience in treatment of ameloblastic tumors showed total biopsy with osseous surgical margins resection to be sufficient for normal bone structure remodeling in some patients.

  20. [Maxillary ameloblastic fibroma: a case report].

    PubMed

    Wang, Hongming; Xue, Weishuang; Yan, Aihui

    2013-12-01

    Ameloblastic fibroma (AF) is a benign tumor, it is a true mixed tumor composed of neoplastic epithelium and mesenchymal. This tumor is rare, and it almost arises in the mandible. A 22-years old female patient referred AF in the maxillary was present. The tumor was asymptomatic, except the right facial bulge. The radiograph showed a well-circumscribed neoplasm with several low density cysts involving the right maxillary and ethmoid. The lesion was enucleated and the material was sent for histopathologic examination. Microscopically, it was composed epithelium and mesenchymal with histopathological diagnosis of ameloblastic fibroma.

  1. Maxillary ameloblastic fibroma in a dog.

    PubMed

    Miles, C R; Bell, C M; Pinkerton, M E; Soukup, J W

    2011-07-01

    A 4-year-old spayed female Golden Retriever was presented for evaluation of a rostral maxillary gingival mass. An en bloc resection was performed after histologic diagnosis of ameloblastic fibroma from an incisional biopsy specimen. Histologically, the tumor was composed of (1) poorly differentiated vimentin-positive mesenchymal cells that surrounded islands and (2) thin anastomosing trabeculae of odontogenic epithelium that variably coexpressed pancytokeratin and vimentin. To the authors' knowledge, this is the first report of ameloblastic fibroma in a dog. The clinical, radiographic, and histologic findings in this case are compared to those in other domestic animals and humans. © The Authors 2011

  2. Aggressive atypical ameloblastic fibrodentinoma: Report of a case.

    PubMed

    Giraddi, Girish B; Garg, Vipul

    2012-01-01

    Ameloblastic fibroma and related lesions constitute a group of lesions, which range in biologic behaviour from true neoplasms to hamartomas. This group of lesions is also sometimes referred to as mixed odontogenic tumors and usually includes ameloblastic fibroma, ameloblastic fibrodentinoma and ameloblastic fibro-odontoma. Despite numerous efforts however, there is still considerable confusion concerning the nature and interrelationship of these mixed odontogenic tumors and related lesions. The malignant counterpart of these lesions namely aameloblastic fibrosarcoma, ameloblastic dentinosarcoma and ameloblastic odontosarcoma respectively are said to arise secondarily in their benign counterpart or de novo. Recurrence of the benign lesion raises the risk towards malignant transformation therefore a radical surgery should be planned inspite of enucleation or curettage. Here we present a case of an aggressive ameloblastic fibrodentinoma which was radically excised in the light of clinical and histological presentation followed by reconstruction of mandible.

  3. Aggressive atypical ameloblastic fibrodentinoma: Report of a case

    PubMed Central

    Giraddi, Girish B.; Garg, Vipul

    2012-01-01

    Ameloblastic fibroma and related lesions constitute a group of lesions, which range in biologic behaviour from true neoplasms to hamartomas. This group of lesions is also sometimes referred to as mixed odontogenic tumors and usually includes ameloblastic fibroma, ameloblastic fibrodentinoma and ameloblastic fibro-odontoma. Despite numerous efforts however, there is still considerable confusion concerning the nature and interrelationship of these mixed odontogenic tumors and related lesions. The malignant counterpart of these lesions namely aameloblastic fibrosarcoma, ameloblastic dentinosarcoma and ameloblastic odontosarcoma respectively are said to arise secondarily in their benign counterpart or de novo. Recurrence of the benign lesion raises the risk towards malignant transformation therefore a radical surgery should be planned inspite of enucleation or curettage. Here we present a case of an aggressive ameloblastic fibrodentinoma which was radically excised in the light of clinical and histological presentation followed by reconstruction of mandible. PMID:22557908

  4. [Ameloblastic transformation of an odontogenic cyst].

    PubMed

    Arita, E S; Fenyo-Pereira, M; Jaeger, R G; Nose, A S; de Freitas, A

    1990-01-01

    The author relate a case of ameloblastic changing in an odontologenic cyst located in the anterior region of the mandible, in a man fifty-four years old. They comment the importance of a complete examination when someone finds a pathology.

  5. 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.

  6. 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.

  7. 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

  8. A massive ameloblastic fibro-odontoma of the maxilla.

    PubMed

    Hegde, Veda; Hemavathy, S

    2008-01-01

    Ameloblastic fibro-odontoma is a rare, benign mixed odontogenic tumor. It occurs exclusively as an intraosseous lesion. It usually has a slow growth and is seen in children and young adults. A painless swelling is the most common clinical sign. Radiographically, ameloblastic fibro-odontoma appears as a circumscribed radiolucency which may contain radiopaque foci. Most cases of ameloblastic fibro-odontoma exhibit benign behavior, but cases of malignant transformation have been reported. The treatment modality in most cases involves conservative surgery, but cases with malignant transformation will require more radical treatment. A massive ameloblastic fibro-odontoma involving the maxilla has been described here with its clinical, radiological, and histopathological features.

  9. Maxillary ameloblastic fibroma: a case report.

    PubMed

    Costa, Daniela Otero Pereira da; Alves, Adriana Terezinha Neves Novellino; Calasans-Maia, Mônica Diuna; Cruz, Ricardo Lopes da; Lourenço, Simone de Queiroz Chaves

    2011-01-01

    Ameloblastic fibroma is a relatively rare benign odontogenic tumor in which both the epithelial and ectomesenchymal components are neoplastic. An 8-year-old Caucasian boy was referred to the dentist for evaluation of failed eruption of the maxillary left first molar. The panoramic radiograph showed a well-circumscribed unilocular radiolucency involving an unerupted maxillary left first permanent molar. The lesion was enucleated and the material was sent for histopathologic examination. Microscopically, it was composed by cords and islands of odontogenic epithelium in a myxoid cell-rich stroma that closely resemble the dental papilla with histopathological diagnosis of ameloblastic fibroma. After 24 months of follow-up no recurrence was observed and the maxillary left first molar erupted spontaneously through the buccal mucosa and was aligned with a fixed orthodontic appliance. This case emphasized the importance of careful differential diagnosis of intraosseous oral lesions and reported a rarity of the lesion and its atypical location.

  10. [An immunohistochemical study of the proliferating activity of ameloblastic fibroma and ameloblastic fibrosarcoma].

    PubMed

    Lu, Y; Takata, T; Wang, L; Zhou, Z; Wu, L; Zhao, M; Nikai, H

    1998-12-01

    Six cases of ameloblastic fibroma (AF) and three cases of ameloblastic fibrosarcoma (AFS) were immunohistochemically investigated with a proliferating cell nuclear antigen (PCNA) monoclone antibody. Data on the PCNA labeling index (LI) of both epithelial and mesenchymal components were analyzed. The results showed that the PCNA LI of mesenchymal component of AFS (40.8%) was significantly higher than that of AF (3.2%) (P < 0.01) and that of the epithelial component of AFS (5.3%) was significantly lower than that of the mesenchymal one of AFS (P < 0.01). The results suggested that PCNA LI be a useful marker for the differentiation diagnosis of AF and AFS.

  11. Hybrid odontogenic tumor of calcifying odontogenic cyst and ameloblastic fibroma.

    PubMed

    Yoon, Jung Hoon; Kim, Hyung Jun; Yook, Jong In; Cha, In Ho; Ellis, Gary L; Kim, Jin

    2004-07-01

    Odontogenic tumors composed of 2 distinct types of lesions are unusual. We report an odontogenic tumor that was composed of calcifying odontogenic cyst and ameloblastic fibroma that occurred in the right posterior maxilla of a 22-year-old Korean woman. The tumor had a cystic component with an ameloblastic epithelial lining and conglomerates of so-called ghost cells, and there were deposits of dentinoid material adjacent to the cyst. These are features characteristic of calcifying odontogenic cyst. Enamel organ-like epithelial islands were observed within a dental papilla-like stroma of the cyst wall. Additionally, a solid portion of the tumor had characteristic features of ameloblastic fibroma, i.e., a myxoid cellular stroma with numerous elongated islands of ameloblastic epithelium. Ghost cell masses were found in the area of ameloblastic fibroma as well. The distribution of the ghost cells suggests that this is a hybrid lesion rather than a collision tumor.

  12. Ameloblastic fibrosarcoma of the jaws. A clinicopathologic and DNA analysis of five cases and review of the literature with discussion of its relationship to ameloblastic fibroma.

    PubMed

    Muller, S; Parker, D C; Kapadia, S B; Budnick, S D; Barnes, E L

    1995-04-01

    Ameloblastic fibrosarcoma, the malignant counterpart of the ameloblastic fibroma, is a rare odontogenic tumor characterized by benign epithelium and a malignant fibrous stroma. We have compared nuclear DNA content of five ameloblastic fibrosarcomas and three ameloblastic fibromas by image analysis. The three ameloblastic fibromas were diploid, whereas 1 of 5 ameloblastic fibrosarcomas was aneuploid. There was no correlation with histologic grade and aneuploidy. These five new cases were also added to a review of the literature, bringing the total cases of reported ameloblastic fibrosarcomas to 51. The ameloblastic fibrosarcoma occurs at a later age (mean, 27.5 years) compared with reported ameloblastic fibromas (mean, 14.6 to 22 years), which supports a step-wise malignant transformation. There was histologic documentation that 44% of ameloblastic fibrosarcomas developed in ameloblastic fibromas. In view of this data and of the reported cumulative recurrence rate of 18.3% for ameloblastic fibroma, it is recommended that ameloblastic fibromas be treated with complete surgical excision and long-term follow up rather than simple curettage or enucleation.

  13. Ameloblastic fibroma of the maxillary sinus.

    PubMed

    Pereira, Kevin D; Bennett, Kristin M; Elkins, Tina P; Qu, Zhenhong

    2004-11-01

    Ameloblastic fibroma is a rare true mixed tumor of odontogenic origin with both mesenchymal and ectodermal components. It usually arises from the mandibular dentition and presents in the second decade of life. It is a benign slow growing tumor that is less infiltrative than an ameloblastoma but tends to expand bone. It infrequently involves the maxilla and hence the management of these tumors in that region is controversial. The goal of therapy is to avoid cosmetic deformity without compromising on tumor eradication. We present the tenth reported case of this type of tumor in the maxilla, and the second one in an infant.

  14. Treatment of a recurrent ameloblastic fibroma.

    PubMed

    Manzon, Steven; Philbert, Rawle F; Bush, Benjamin F; Zola, Malcolm B; Solomon, Marshall

    2015-01-01

    Ameloblastic fibroma (AF), a slow-growing, benign tumor of odontogenic origin, represents 2% of all odontogenic tumors. Jaw expansion is among the most common symptoms, with diagnosis often made through routine radiographs. AFs have a recurrence rate of 18% to 43.5% after conservative enucleation. Long-term follow-up by both the surgeon and referring dentist is recommended, since recurrence may be due to regrowth of residual tumor undergoing malignant transformation. Aggressive management is recommended for local tumor recurrence. En bloc excision with bone grafting, followed by implant reconstruction, can be curative and preservative of function. Treatment of a recurrent AF is described.

  15. 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

  16. 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.

  17. [Ameloblastic fibro-odontoma of the maxillary sinus].

    PubMed

    Nouri, H; Raji, A; Ait M'barek, B

    2007-11-01

    Ameloblastic fibro-odontoma, ameloblastic fibroma, and odontoma are rare malformations, which are classified as odontologic tumors. They usually progress in an asymptomatic way, and making the histological distinction between these variants is very difficult. We report the case of a 14-year-old girl presenting with an ameloblastic fibro-odontoma of the maxillary sinus. The clinical signs were nasal obstruction and jugular tumefaction. Surgical excision was performed through a paralateronasal approach. The diagnosis of fibro-odontoma was confirmed by the histopathological analysis of the surgical piece. Odontologic tumors form a complex entity, the histological nature and the correlations of which are discussed.

  18. Ameloblastic Fibrodentinoma: A Case with Varied Patterns of Dysplastic Dentin.

    PubMed

    Bavle, Radhika M; Muniswammappa, Sudhakara; Venugopal, Reshma; R, Amulya S

    2017-06-14

    Ameloblastic fibrodentinoma is a benign odontogenic tumor belonging to the category of "odontogenic epithelium with odontogenic ectomesenchyme" along with recognition of induction in the form of dentin in atypical or dysplastic forms. The biological behaviour of ameloblastic fibrodentinoma is not very different from ameloblastic fibroma; hence, it is treated similarly by conservative procedures. It is important to understand the histopathogenesis of these rare tumors. Though rare, they are an independent entity awaiting recognition. Here, we report a case of amelobalstic fibrodentinoma in a 14-year-old female patient.

  19. Ameloblastic Fibrodentinoma: A Case with Varied Patterns of Dysplastic Dentin

    PubMed Central

    Bavle, Radhika M; Muniswammappa, Sudhakara; R, Amulya S

    2017-01-01

    Ameloblastic fibrodentinoma is a benign odontogenic tumor belonging to the category of "odontogenic epithelium with odontogenic ectomesenchyme" along with recognition of induction in the form of dentin in atypical or dysplastic forms. The biological behaviour of ameloblastic fibrodentinoma is not very different from ameloblastic fibroma; hence, it is treated similarly by conservative procedures. It is important to understand the histopathogenesis of these rare tumors. Though rare, they are an independent entity awaiting recognition. Here, we report a case of amelobalstic fibrodentinoma in a 14-year-old female patient. PMID:28721317

  20. Peripheral Ameloblastic Fibroma: Report of a Rare Case

    PubMed Central

    Kalantari, Mahsa; Samieirad, Sahand; Kalantari, Parisa

    2016-01-01

    Ameloblastic fibroma is a rare mixed odontogenic tumor mostly occurring in the posterior region of the mandible. The peripheral variant is very rare and to the best of our knowledge, only three cases have been reported in the English literature. In this report, we describe a case of peripheral ameloblastic fibroma in a 54-year-old woman with two years of follow-up. PMID:27942554

  1. Congenital ameloblastic fibroma in association with oculoauriculovertebral spectrum.

    PubMed

    Naidoo, L C; Stephen, L X

    1998-05-15

    Although orodental anomalies have been reported to occur in patients with oculoauriculovertebral spectrum, no previous publications in the English literature have been located that describe an ameloblastic fibroma in a patient with this condition. This report presents a 15-month-old female monozygotic twin with concomitant oculoauriculovertebral spectrum and a congenital ameloblastic fibroma of the mandible. A theory linking the pathogenesis of the two conditions is also raised.

  2. Peripheral Ameloblastic Fibroma: Report of a Rare Case.

    PubMed

    Kalantari, Mahsa; Samieirad, Sahand; Kalantari, Parisa

    2016-12-01

    Ameloblastic fibroma is a rare mixed odontogenic tumor mostly occurring in the posterior region of the mandible. The peripheral variant is very rare and to the best of our knowledge, only three cases have been reported in the English literature. In this report, we describe a case of peripheral ameloblastic fibroma in a 54-year-old woman with two years of follow-up.

  3. Ameloblastic Fibrosarcoma Arising in the Maxilla.

    PubMed

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

    2016-01-01

    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. 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. 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.

  4. 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

  5. Ameloblastic Fibro-Odontoma: A Diagnostic Challenge

    PubMed Central

    Tolentino, Elen de Souza; Centurion, Bruna Stuchi; Lima, Marta Cunha; Freitas-Faria, Patrícia; Consolaro, Alberto; Sant'ana, Eduardo

    2010-01-01

    An 11-year-old girl presented to our department to have a second opinion regarding a lesion involving her left mandible. She had previously undergone several radiographic exams including panoramic, helical, and cone-beam computed tomography. Radiographic examinations revealed a well-defined radiolucent region, which contained an irregular radiopaque mass of 3 cm in diameter, localized to the left angle of the mandible. Our presumptive diagnosis was complex odontoma. Excisional biopsy was performed, and microscopic features showed strands and islands of odontogenic epithelium showing peripheral palisading and loosely arranged central cells, identical to stellate reticulum, embedded in a myxoid cell-rich stroma resembling the dental papilla. Dentin and enamel were also presented. The diagnosis was ameloblastic fibro-odontoma, which is a rare mixed odontogenic tumor, derived from epithelial and ectomesenchymal elements that form the dental tissues. PMID:20827417

  6. Ameloblastic fibro-odontoma masquerading as odontoma.

    PubMed

    Nanda, Kanwar Deep Singh; Marwaha, Mohita

    2011-01-01

    Ameloblastic fibro-odontoma (AFO) is a rare, benign epithelial mixed odontogenic tumor. It occurs as an intraosseous lesion, generally asymptomatic and more prevalent in children and adolescent. AFO is found on radiographic evaluation of patients with unerupted or impacted teeth in many cases. Histological examination reveals a fibrous soft tissue, islands of odontogenic epithelium and a disordered mixture of dental tissues. The treatment modality in most cases involves conservative surgery with enucleation. We present a case of 13-year-old boy with a missing right central incisor, mimicking-like odontoma on radiograph but proved to be AFO and treated with enucleation with preservation of impacted tooth. There was no recurrence after one year of follow-up. This report discusses the clinical, radiographical, histological features and surgical assessment to preserve the impacted tooth associated with AFO.

  7. Adenoid Cystic Carcinoma of the Skull Base

    PubMed Central

    Issing, Peter R.; Hemmanouil, Ilias; Stöver, Timo; Kempf, Hans-Georg; Wilkens, L.; Heermann, R.; Lenarz, Thomas

    1999-01-01

    Adenoid cystic carcinoma (ACC) is a slowly growing tumor with a particular tendency to infiltrate the surrounding tissue by perineural spread. The clinical diagnosis may prove difficult due to the submucons extension of the tumor, especially at the skull base. This article outlines the clinical characteristics, diagnostics, and treatment modalities in a series of 56 patients with an ACC in the head and neck diagnosed between 1970 and 1998 in 32 females and 24 males. The youngest patient was aged 24 years, the oldest 77 years. The average age was 54 years. In 16 patients the tumor originated in the paranasal sinuses or the nasopharynx and involved the skull base. As a rule, several months passed between the manifestation of the first symptoms such as pain, blocked nose, epistaxis, or diplopia and the initial clinical diagnosis. All patients received surgical treatment, however, complete microscopical resection could only be achieved in approximately one third of the cases. Therefore, nine patients were postoperatively treated with radiotherapy. The average survival rates of the patients with an ACC of the skull base were only 99 months as compared to 144 months in the patients without skull base involvement. ImagesFigure 1 PMID:17171116

  8. MMP20 modulates cadherin expression in ameloblasts as enamel develops.

    PubMed

    Guan, X; Bartlett, J D

    2013-12-01

    Matrix metalloproteinase-20 (enamelysin, MMP20) is essential for dental enamel development. Seven different MMP20 mutations in humans cause non-syndromic enamel malformations, termed amelogenesis imperfecta, and ablation of Mmp20 in mice results in thin brittle enamel with a dysplastic rod pattern. Healthy enamel formation requires the sliding movement of ameloblasts in rows during the secretory stage of development. This is essential for formation of the characteristic decussating enamel rod pattern observed in rodents, and this is also when MMP20 is secreted into the enamel matrix. Therefore, we propose that MMP20 facilitates ameloblast movement by cleaving ameloblast cell-cell contacts. Here we show that MMP20 cleaves the extracellular domains of the E- and N-cadherin adherens junction proteins, that both E- and N-cadherin transcripts are expressed at significantly higher levels in Mmp20 null vs. wild-type (WT) mice, and that in Mmp20 ablated mice, high-level ameloblast N-cadherin expression persists during the maturation stage of development. Furthermore, we show that E-cadherin gene expression is down-regulated from the pre-secretory to the secretory stage, while N-cadherin levels are up-regulated. This E- to N-cadherin switch supports epithelial migration in other tissues and may be an important event necessary for the ameloblasts to start moving in rows that slide by one another.

  9. MMP20 Modulates Cadherin Expression in Ameloblasts as Enamel Develops

    PubMed Central

    Guan, X.; Bartlett, J.D.

    2013-01-01

    Matrix metalloproteinase-20 (enamelysin, MMP20) is essential for dental enamel development. Seven different MMP20 mutations in humans cause non-syndromic enamel malformations, termed amelogenesis imperfecta, and ablation of Mmp20 in mice results in thin brittle enamel with a dysplastic rod pattern. Healthy enamel formation requires the sliding movement of ameloblasts in rows during the secretory stage of development. This is essential for formation of the characteristic decussating enamel rod pattern observed in rodents, and this is also when MMP20 is secreted into the enamel matrix. Therefore, we propose that MMP20 facilitates ameloblast movement by cleaving ameloblast cell-cell contacts. Here we show that MMP20 cleaves the extracellular domains of the E- and N-cadherin adherens junction proteins, that both E- and N-cadherin transcripts are expressed at significantly higher levels in Mmp20 null vs. wild-type (WT) mice, and that in Mmp20 ablated mice, high-level ameloblast N-cadherin expression persists during the maturation stage of development. Furthermore, we show that E-cadherin gene expression is down-regulated from the pre-secretory to the secretory stage, while N-cadherin levels are up-regulated. This E- to N-cadherin switch supports epithelial migration in other tissues and may be an important event necessary for the ameloblasts to start moving in rows that slide by one another. PMID:24067343

  10. Ghost cell differentiation and calcification in ameloblastic fibroma.

    PubMed

    Luo, Hai Yan; Gao, Yan

    2013-01-01

    Ghost cell differentiation within an ameloblastic fibroma is extremely rare. The ghost cells found in an ameloblastic fibroma in previously reported cases were all associated with a typical calcifying odontogenic cyst. Here, we report a case of an ameloblastic fibroma with focal ghost cells and calcifications in some neoplastic epithelial islands, but without other histologic manifestations consistent with a calcifying odontogenic cyst. The patient was a 13-year-old Chinese boy who presented with a bony-hard swelling in the posterior mandibular region over a 6-month period. Radiographs showed a well-defined multilocular radiolucency associated with an unerupted tooth. The lesion was mostly cystic-solid and comprised of odontogenic epithelial strands, islands and myxoid ectomesenchymal component microscopically. Small groups of ghost cells and calcification were noted in the epithelial islands.

  11. A large ameloblastic fibro-odontoma of the right mandible.

    PubMed

    Oghli, Ayham Arab; Scuto, Ignazio; Ziegler, Christoph; Flechtenmacher, Christa; Hofele, Christof

    2007-01-01

    The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in children and young adults with no sex predilection and locates most often in the posterior segment of the mandible. A painless swelling is the most common clinical sign. Radiologically, ameloblastic fibro-odontoma shows a circumscribed radiolucency, which contains radio-opaque foci of various sizes and shapes. Histological examination reveals a fibrous soft tissue, islands of odontogenic epithelium and a disordered mixture of dental tissues. The tumor produces enamel or enamel matrix, dentin and cementum. The treatment of ameloblastic fibro-odontomas usually consists of enucleation or surgical curettage, which is possible due to their benign biological behaviour.

  12. Assessment of growth potential by MIB-1 immunohistochemistry in ameloblastic fibroma and related lesions of the jaws compared with ameloblastic fibrosarcoma.

    PubMed

    Sano, K; Yoshida, S; Ninomiya, H; Ikeda, H; Ueno, K; Sekine, J; Iwamoto, H; Uehara, M; Inokuchi, T

    1998-02-01

    Specimens from two ameloblastic fibromas (including one recurrent case), two ameloblastic fibro-odontomas, and one ameloblastic fibrosarcoma were subjected to investigation by MIB-1 immunohistochemistry in order to elucidate the growth potential of these tumors. MIB-1 labeling indices in the epithelial component of these tumors ranged from 2.9 to 7.5%, whereas those in the mesenchymal component ranged from 1.5 to 13.5%. Of these, labeling indices in the mesenchymal component of the recurrent ameloblastic fibroma and ameloblastic fibrosarcoma were quite high. These findings suggest that evaluation of growth potential in ameloblastic fibroma and related lesions could be of help in understanding tumor aggressiveness and in selecting appropriate surgical procedures.

  13. 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.

  14. 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.

  15. Ameloblastic Fibrosarcoma of the Mandible With Distant Metastases.

    PubMed

    Pourdanesh, Fereydoun; Mohamadi, Mansoureh; Moshref, Mohammad; Soltaninia, Omid

    2015-10-01

    Ameloblastic fibrosarcoma is a mixed odontogenic tumor that can originate de novo or from a transformed ameloblastic fibroma. This report describes the case of a 34-year-old woman with a recurrent, rapidly growing, debilitating lesion. This lesion appeared as a large painful mandibular swelling that filled the oral cavity and extended to the infratemporal fossa. The lesion had been previously misdiagnosed as ameloblastoma. Twenty months after final surgery and postoperative chemotherapy, lung metastases were diagnosed after she reported respiratory signs and symptoms. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Ameloblastic fibrodentinoma involving anterior maxilla: a rare case report.

    PubMed

    Sankireddy, Shailaja; Kaushik, Atul; Krishna, Bhargavi A; Reddy, Asha Latha G; Vinod, V C; Sridevi, V

    2013-01-01

    Ameloblastic fibroma (AF) and related lesions comprise a complex group of mixed odontogenic tumors. Ameloblastic fibrodentinoma (AFD) is a rare tumor and is considered as a histological variant of AF showing inductive changes that lead to the formation of dentin. Although the most common site for this tumor is the posterior mandible, hereby we are reporting a case of AFD in the anterior maxillary region which is a very rare site for this group of tumors. The present case report highlights the clinical, radiological and histological presentation of AFD in order to raise awareness for the earlier diagnosis and precise management of this rare pathological entity.

  17. 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

  18. Anaplastic ameloblastic fibrosarcoma arising from recurrent ameloblastic fibroma: restricted molecular abnormalities of certain genes to the malignant transformation.

    PubMed

    Williams, Michelle D; Hanna, Ehab Y; El-Naggar, Adel K

    2007-07-01

    A rare case of anaplastic ameloblastic fibrosarcoma (AS) arising in an ameloblastic fibroma (AF) of the maxilla of a 48-year-old patient 10 years after the primary excision is presented. The recurrent tumor retained focal areas of AF but manifested heterogeneous malignant features ranging from low-grade spindle to highly pleomorphic sarcomas. Biomarker analysis showed alterations of the p53 and c-KIT genes restricted to the sarcomatous component. The biological implications of these findings in the future management of these tumors are discussed.

  19. 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. © The Author(s) 2016.

  20. 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

  1. Ameloblastic odontoma in the mandible of a llama

    PubMed Central

    Step, Douglas L.; Ritchey, Jerry W.; Drost, William Tod; Bahr, Robert J.

    2003-01-01

    A 4-year-old llama had an aggressive, multiloculated, expansile bone lesion involving the rostral mandible. The mandibular lesion was imaged using radiography and computed tomography. Antemortem diagnosis of an ossifying fibroma was made histologically. Postmortem findings showed the lesion to be limited to the mandible. Final diagnosis was ameloblastic odontoma. PMID:14601679

  2. Enamelin Is Critical for Ameloblast Integrity and Enamel Ultrastructure Formation

    PubMed Central

    Hu, Jan C.-C.; Hu, Yuanyuan; Lu, Yuhe; Smith, Charles E.; Lertlam, Rangsiyakorn; Wright, John Timothy; Suggs, Cynthia; McKee, Marc D.; Beniash, Elia; Kabir, M. Enamul; Simmer, James P.

    2014-01-01

    Mutations in the human enamelin gene cause autosomal dominant hypoplastic amelogenesis imperfecta in which the affected enamel is thin or absent. Study of enamelin knockout NLS-lacZ knockin mice revealed that mineralization along the distal membrane of ameloblast is deficient, resulting in no true enamel formation. To determine the function of enamelin during enamel formation, we characterized the developing teeth of the Enam−/− mice, generated amelogenin-driven enamelin transgenic mouse models, and then introduced enamelin transgenes into the Enam−/− mice to rescue enamel defects. Mice at specific stages of development were subjected to morphologic and structural analysis using β-galactosidase staining, immunohistochemistry, and transmission and scanning electron microscopy. Enamelin expression was ameloblast-specific. In the absence of enamelin, ameloblasts pathology became evident at the onset of the secretory stage. Although the aggregated ameloblasts generated matrix-containing amelogenin, they were not able to create a well-defined enamel space or produce normal enamel crystals. When enamelin is present at half of the normal quantity, enamel was thinner with enamel rods not as tightly arranged as in wild type suggesting that a specific quantity of enamelin is critical for normal enamel formation. Enamelin dosage effect was further demonstrated in transgenic mouse lines over expressing enamelin. Introducing enamelin transgene at various expression levels into the Enam−/− background did not fully recover enamel formation while a medium expresser in the Enam+/− background did. Too much or too little enamelin abolishes the production of enamel crystals and prism structure. Enamelin is essential for ameloblast integrity and enamel formation. PMID:24603688

  3. Peripheral ameloblastic fibroma of the maxilla: report of a case and review of the literature.

    PubMed

    Abughazaleh, Khaled; Andrus, Kevin M; Katsnelson, Alexander; White, Dean K

    2008-05-01

    Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. Also referred to as extraosseous or soft tissue odontogenic tumors, peripheral odontogenic tumors share the same histopathologic characteristics of their central or intraosseous counterparts. Ameloblastic fibroma is a rare odontogenic tumor that arises from both odontogenic epithelium and connective tissue. Only 2 cases of peripheral ameloblastic fibroma have been reported in the English-language literature, one of which did not show the classic features of an ameloblastic fibroma. In this report, we describe a rare case of a peripheral ameloblastic fibroma in the maxilla of a 3-year-old girl.

  4. 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.

  5. An unusual size of ameloblastic fibro-odontoma.

    PubMed

    Dolanmaz, D; Pampu, A A; Kalayci, A; Etöz, O A; Atici, S

    2008-03-01

    Ameloblastic fibro-odontoma (AFO) is a quite rare, mixed odontogenic tumour generally seen in the early stages of life. Frequent signs of the tumour are asymptomatic swelling, delayed tooth eruption and mixed radiological appearance within well-defined borders. Management of the lesion includes enucleation of the tumour and long-term follow-up in order to avoid recurrence. A 9-year-old girl was referred to our clinic with swelling in her right cheek. After clinical and radiographic examination, a large lobular radiopaque mass with a radiolucent border covering the complete right maxillary sinus was observed. Under general anaesthesia, the lobules of the lesion were enucleated and the permanent right lateral incisor and canine teeth were left for eruption. Histological assessment revealed a final diagnosis of ameloblastic fibro-odontoma. Post-operative healing was uneventful and the remaining teeth erupted normally. No recurrence was observed during the 3 years' follow-up period.

  6. Ameloblastic fibroma of the mandible. Report of two cases.

    PubMed

    Martín-Granizo López, Rafael; Ortega, Luis; González Corchón, Ma Aránzazu; Berguer Sández, Alberto

    2003-01-01

    The ameloblastic fibroma (AF)-ameloblastic fibro-odontoma (AFO), is an uncommon benign mixed odontogenic tumor (epithelial and mesenchymal), that represents the 2% of all odontogenic tumors. It usually appears in the mandible and in the posterior segments of young patients without gender predilection, and sometimes is associated with an impacted tooth. The classification of the WHO includes it in the subtype of odontogenic tumors with a defined histologic features. The AF and the AFO are considered as an unique entity as they are variations of the same tumor, only distinct for the presence of an odontoma in the case of the AFO. Surgical conservative treatment with excision followed by curettage seems to be the most appropriate therapeutic option. The objective of this paper is to report two cases of this tumor, to make a brief review of the literature and its differential diagnosis, to analyse its clinical and histologic features and the therapeutic option.

  7. A delayed presentation of ameloblastic fibrosarcoma in an African patient.

    PubMed

    Chauke, Nkhensani Yvonne; Sofianos, Chrysis; Liakos, Dimitri; Ndobe, Elias

    2017-08-01

    A 24-year-old womanpresented with ameloblastic fibrosarcoma arising from ameloblastic fibroma. The delayed presentation accounted for the extensive destruction of the mandible and complete occlusion of her oral cavity. This resulted in an inability to eat and maintain oral hygiene. A multidisciplinary team management approach involved nutritional optimisation, segmental mandibulectomy, reconstruction with a reconstructive plate and a free anterolateral thigh flap to line the the floor of mouth. Functional and aesthetic outcome was acceptable, and the patient is planned for secondary free fibular flap bony reconstruction. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. 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.

  9. Recurrent Ameloblastic Fibroma: Report of a Rare Case

    PubMed Central

    Kulkarni, Ravikumar S.; Sarkar, Amitabh; Goyal, Sandeep

    2013-01-01

    Ameloblastic fibroma (AF) is an uncommon mixed neoplasm of odontogenic origin frequently seen in the second decade of life. It mainly presents as an intrabony lesion but can even occur peripherally. Histologically, our case showed hypercellular areas, an uncommon feature seen in typical AF. Whether this benign lesion is treated by mode of enucleation and curettage or by extensive surgery is still a topic of debate. An extensive surgical treatment is suggested as the initial approach due to its high recurrence rate (18%) and the greater chances of recurrent AFs transforming into ameloblastic fibrosarcoma (45%), together with a long-term followup. We report a case of recurrent AF with hypercellular ectomesenchyme which developed a year after its conservative removal. We conclude that in recurrent AF sufficient sections of the pathological specimen are to be taken to rule out any malignant changes that might have begun in focal areas. PMID:23762647

  10. Recurrent ameloblastic fibroma: report of a rare case.

    PubMed

    Kulkarni, Ravikumar S; Sarkar, Amitabh; Goyal, Sandeep

    2013-01-01

    Ameloblastic fibroma (AF) is an uncommon mixed neoplasm of odontogenic origin frequently seen in the second decade of life. It mainly presents as an intrabony lesion but can even occur peripherally. Histologically, our case showed hypercellular areas, an uncommon feature seen in typical AF. Whether this benign lesion is treated by mode of enucleation and curettage or by extensive surgery is still a topic of debate. An extensive surgical treatment is suggested as the initial approach due to its high recurrence rate (18%) and the greater chances of recurrent AFs transforming into ameloblastic fibrosarcoma (45%), together with a long-term followup. We report a case of recurrent AF with hypercellular ectomesenchyme which developed a year after its conservative removal. We conclude that in recurrent AF sufficient sections of the pathological specimen are to be taken to rule out any malignant changes that might have begun in focal areas.

  11. Ameloblastic fibrosarcoma of the jaw: report of five cases.

    PubMed

    Dallera, P; Bertoni, F; Marchetti, C; Bacchini, P; Campobassi, A

    1994-12-01

    Five cases of ameloblastic fibrosarcomas (AFS) are reported. The tumour was characterized histologically by a biphasic pattern: the malignant mesenchymal component had the features of an intermediate grade fibrosarcoma in 3 cases, malignant fibrous histiocytoma and osteogenic sarcoma in 2 cases. The epithelial odontogenic component had a benign appearance cytologically. In 1 patient, in the recurrence only the malignant mesenchymal component was present. AFS is a fully malignant tumour, in fact 1 patient died of the tumour after inadequate surgical treatments, and 2 patients had a recurrence after intralesional surgery. The treatment of choice was achieved when surgery with wide surgical margins was performed. As MFH and OGS features are present in the malignant mesenchymal component of this tumour we prefer to use the broad term ameloblastic sarcoma instead of AFS.

  12. Ameloblastic fibroma: a case report in a 6 year old.

    PubMed

    Garcia-Pola Vallejo, M; Gonsalez Garcia, M; Villalain Alvarez, L; Fresno Forcedello, M; Lopez-Arranz, J S

    2001-01-01

    A six-year-old boy was seen by his dentist for a tumor mass in the left mandibular region. The panograph revealed a multilocular radiotransparent lesion extending from the canine to the left mandibular ascending ramus with well defined borders. After biopsy, the lesion was enucleated via curettage of the bone bed. The lesion was diagnosed as ameloblastic fibroma. After six months, radiographs showed that the surgical defect had filled with new bone.

  13. Ameloblastic fibro-odontoma: report of two cases.

    PubMed

    Favia, G F; Di Alberti, L; Scarano, A; Piattelli, A

    1997-11-01

    Ameloblastic fibro-odontoma is a rare odontogenic tumour. It affects young people and is usually located in the posterior jaws. Two cases of this tumour are presented: both lesions had produced an asymptomatic swelling. The histology showed the presence of an odontogenic epithelium immersed in a fibrous mesenchyme; dental hard tissues were also present. No recurrences were found after 12 and 4 years from the surgical enucleation of the tumour.

  14. Odontogenic ameloblasts-associated protein (ODAM), via phosphorylation by bone morphogenetic protein receptor type IB (BMPR-IB), is implicated in ameloblast differentiation.

    PubMed

    Lee, Hye-Kyung; Park, Jong-Tae; Cho, Young-Sik; Bae, Hyun-Sook; Cho, Moon-Il; Park, Joo-Cheol

    2012-05-01

    To elucidate the function of the odontogenic ameloblast-associated protein (ODAM) in ameloblasts, we identified more than 74 proteins that interact with ODAM using protoarray. Of the identified proteins, bone morphogenetic protein receptor type-IB (BMPR-IB) was physiologically relevant in differentiating ameloblasts. ODAM and BMPR-IB exhibited similar patterns of expression in vitro, during ameloblast differentiation. ODAM and BMPR-IB interacted through the C-terminus of ODAM, which resulted in increased ODAM phosphorylation in the presence of bone morphogenetic protein 2 (BMP-2). Immunoprecipitation assays using Ser-Xaa-Glu (SXE) mutants of ODAM demonstrated that the phosphorylation of ODAM by BMPR-IB occurs at this motif, and this phosphorylation is required for the activation of MAPKs. ODAM phosphorylation was detected in ameloblasts during ameloblast differentiation and enamel mineralization in vitro and involved in the activation of downstream factors of MAPKs. Therefore, the BMP-2-BMPR-IB-ODAM-MAPK signaling cascade has important roles in ameloblast differentiation and enamel mineralization. Our data suggest that ODAM facilitates the progression of tooth development in cooperation with BMPR-IB through distinct domains of ODAM.

  15. Ameloblastic fibroma in the midline of mandible: a case report.

    PubMed

    Mohapatra, P K; Choudhury, A R; Parkash, H

    2000-01-01

    The ameloblastic fibroma (AF) is a rare benign mixed odontogenic tumor. It is composed of both epithelial and mesenchymal elements, but lacks of any calcified dental structures. Most of these tumors occur in the mandible and appears preferentially in the posterior portion of the dental arch with molar area predominates over premolar area. It is important to differentiate the lesion from ameloblastoma, since unlike the latter, it does not exhibit a locally invasive growth pattern. It is a well-circumscribed lesion and does not require the radical excision that may be necessary to effect cure with ameloblastoma. The present case report describes a 15-year-old patient with an ameloblastic fibroma in the symphysis of the mandible, a rare reported site. In the beginning of the article an extensive review of the previously published literature on ameloblastic fibroma has been made. In the later part, the diagnosis, differential diagnosis, histology and therapeutic procedures and postoperative follow up of the present case have been described.

  16. Treatment of large ameloblastic fibroma: a case report.

    PubMed

    Vasconcelos, Belmiro C E; Andrade, Emanuel S S; Rocha, Nelson S; Morais, Hécio H A; Carvalho, Ricardo W F

    2009-06-01

    Ameloblastic fibroma (AF) is an extremely rare true mixed benign tumor that can occur in either the mandible or the maxilla, but is most frequently found in the posterior region of the mandible. It usually occurs in the first two decades of life and is associated with tooth enclosure, causing a delay in eruption or altering the dental eruption sequence. AF is diagnosed on routine radiographic evaluation and is clinically and radiographically similar to ameloblastic fibrodontoma and odontoma, which makes an accurate diagnosis mandatory. There is controversy in the literature as to whether treatment should be conservative or agressive. A conservative treatment strategy, such as enucleation and curettage, is usually sufficient. However, extensive lesions require radical treatment. We describe a case of ameloblastic fibroma with a very unusual clinical manifestation: it demonstrated considerable extension but no associated impacted tooth, was located in the anterior region of the mandible, and became symptomatic in the fifth decade of life. A radical surgical approach was taken, with immediate reconstruction.

  17. Ameloblastic fibroma at the University of Nairobi Dental Hospital.

    PubMed

    Chindia, M L; Akama, M K; Awange, D O

    2005-08-01

    To document the occurrence of cases of ameloblastic fibroma. A retrospective study. The Division of Oral Pathology and Oral Medicine histopathology laboratory at the Faculty of Dental Sciences, University of Nairobi, January 1991 to December 2000. Seven complete records of histopathologically confirmed cases of ameloblastic fibroma were identified. There were four male and three female cases with an age range of 10 to 22 years (mean=14 years). Remarkably, six of the cases had lesions in the molar regions of the mandible with a single case with a maxillary molar area lesion. One of the cases had the neoplasm associated with an unerupted tooth. From the clinical notes all the patients were managed by meticulous enucleation and curettage of the lesions. After follow up periods ranging from several months to eight years no recurrences had been recorded. Evidently ameloblastic fibroma is an uncommon neoplasm as noted in the earlier literature. Although the lesions can be quite extensive at the time of diagnosis, the recurrence rate appears to be relatively low if the neoplasms are meticulously extirpated.

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

    PubMed

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

    2015-08-18

    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.

  19. Ameloblastic fibrosarcoma: report of a case. Immunohistochemical study and review of the literature.

    PubMed

    Huguet, P; Castellví, J; Avila, M; Alejo, M; Autonell, F; Basas, C; Bescos, M S

    2001-01-01

    Ameloblastic fibrosarcoma is a rare malignant odontogenic tumour characterized by a benign epithelial component within a malignant fibrous stroma. Its behaviour is relatively benign, with absence of metastatic disease, and the prognosis is reported to be good. It is a paradoxical neoplasm with "sarcomatous" morphological and immunohistochemical patterns but with a favourable clinical course. We report a new case of this tumour in a mandibular ramus of a 31-years-old male patient, that was surgically excised and treated with adjuvant chemotherapy and radiotherapy. Five years later the patient is free of disease. The growth potential of ameloblastic fibrosarcoma is evaluated and compared with a related lesion, the ameloblastic fibroma. The sarcomatous mesenchymal component of ameloblastic fibrosarcoma is positive to Ki67, PCNA and p53, in front of the negativity of ameloblastic fibroma.

  20. Ameloblastic fibroma in one-year-old girl

    PubMed Central

    Munde, Anita D; Karle, Ravindra R; Kale, Ujwala B

    2013-01-01

    Ameloblastic fibroma (AF) is a relatively rare, slow growing benign mixed odontogenic tumor, comprising of 1.5-4.5% of all odontogenic tumors. It is usually asymptomatic except for the eventual expansion of the jaw. AFs are most common in adolescents and young adults, mostly affecting the mandible as a well-defined uni or multilocular radiolucency. The effective surgical treatment includes enucleation and curettage of the surrounding bone and removal of the affected teeth. Although recurrence of AF is rare, a long term follow up is recommended. This report describes a 1-year-old girl with AF in the mandible and discusses its clinical, radiographic and histological findings. PMID:23798857

  1. Ameloblastic fibroma diagnosis, treatment and propensity for misidentification.

    PubMed

    Gish, Joshua E; Lessin, Michael E

    2013-04-01

    We present a case of a young male with a radiolucency of the posterior mandible that was diagnosed as an ameloblastic fibroma, a mixed lesion derived from odontogenic epithelium and ectomesenchyme. This case report highlights a potential pitfall of this entity that may lead to inaccurate identification and treatment. Initial frozen section analysis yielded a diagnosis of odontogenic myxoma due to histologic similarities. Our report and discussion help to reacquaint the general practitioner with this entity and emphasize the need for routine screening radiographs and close clinical correlation whenever a microscopic diagnosis is rendered.

  2. Ameloblastic fibroma in one-year-old girl.

    PubMed

    Munde, Anita D; Karle, Ravindra R; Kale, Ujwala B

    2013-01-01

    Ameloblastic fibroma (AF) is a relatively rare, slow growing benign mixed odontogenic tumor, comprising of 1.5-4.5% of all odontogenic tumors. It is usually asymptomatic except for the eventual expansion of the jaw. AFs are most common in adolescents and young adults, mostly affecting the mandible as a well-defined uni or multilocular radiolucency. The effective surgical treatment includes enucleation and curettage of the surrounding bone and removal of the affected teeth. Although recurrence of AF is rare, a long term follow up is recommended. This report describes a 1-year-old girl with AF in the mandible and discusses its clinical, radiographic and histological findings.

  3. 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.

  4. Expression of tenascin and nucleolar organizer region in ameloblastoma and ameloblastic fibroma.

    PubMed

    Carnelio, Sunitha; Vij, Hitesh

    2010-03-01

    The aim of this study was to assess the expression, distribution and comparison of tenascin, a glycoprotein of the extracellular matrix in ameloblastoma and ameloblastic fibroma, both odontogenic neoplasms with diverse biological behavior and to understand the proliferative activity by using the morphometric analysis. Paraffin embedded tissue from 25 cases of odontogenic tumors i.e., ameloblastoma (n = 15) and ameloblastic fibroma (n = 10) were used. The expression of tenascin was evaluated using immunohistochemistry. Morphometric analysis of nucleolar organizer regions (NORs) from ameloblastoma and ameloblastic fibroma was carried out by silver staining. A heterogeneous expression of tenascin was found in ameloblastoma which was mainly localized at the epithelial-mesenchymal interface and a patchy distribution was observed in the stroma (80%), while strong positivity was observed in the stroma and at the basement membrane zone of ameloblastic fibroma (100%). argyrophilic nucleolar organizer regions (AgNORs) revealed higher mean counts in ameloblastoma (3.093 +/- 0.902) when compared with those of ameloblastic fibroma (1.553 +/- 0.250). Ameloblastoma presented more than two NORs (two to five) per nucleus in majority of the cells, while ameloblastic fibroma exhibited only one NORs per nucleus. Expression of tenascin in these neoplasms suggest that it could play a role in epithelial- mesenchymal interaction, while AgNORs reveal that ameloblastomas are more aggressive when compared with ameloblastic fibromas.

  5. 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

  6. 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.

  7. 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.

  8. Ameloblastic fibroma of the anterior maxilla presenting as a complication of tooth eruption: a case report.

    PubMed

    McGuinness, N J; Faughnan, T; Bennani, F; Connolly, C E

    2001-06-01

    Ameloblastic fibroma is a rare mixed odontogenic tumour, which is extremely uncommon in the anterior maxillary region. A case report is presented where failure of eruption of an upper central incisor was the presenting feature.

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

    PubMed Central

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

    2012-01-01

    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. PMID:23166172

  10. 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

  11. 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. © 2013 Eur J Oral Sci.

  12. 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.

  13. Ameloblastic fibro-odontoma: a conservative surgical approach.

    PubMed

    Nascimento, Jairo-Evangelista; Araújo, Leonardo-de Jesus; Almeida, Luciana-Yamamoto de; De Paula, Alfredo-Maurício; Bonan, Paulo-Rogério

    2009-12-01

    Ameloblastic fibro-odontoma (AFO) is a rare benign mixed odontogenic tumor that occurs predominantly in children and young adults with no gender predilection and anatomic site, usually appearing as a painless swelling. We present a case of an 11-year-old non-Caucasian boy complaining of large painless isolated swelling in the right mandibular body. Intraoral examination revealed a tumoral mass with cortical bone expansion, covered by normal mucosa measuring 4.0 x 2.0 cm, located on both the lingual and buccal surfaces of the right body of the mandible, with displacement of the neighboring teeth. Panoramic radiography revealed an expansile, radiolucent and well circumscribed lesion with scattered foci of calcified material, which contained several radiopaque bodies of varying sizes and shapes. The provisional diagnoses were odontoma or AFO/ Biopsy confirmed AFO. The patient was treated with conservative surgery. After two years of follow-up, no alteration or recurrence was detected.

  14. Ameloblastic fibroma or fibrosarcoma: A dilemma of oral surgeon.

    PubMed

    Verma, Nitin; Neha

    2016-01-01

    Ameloblastic fibroma (AF) is an uncommon true mixed odontogenic tumor, with a relative frequency between 1.5% and 4.5% of all odontogenic tumors. It may behave either as a true neoplasm or as a hamartomatous proliferation of odontogenic epithelium of the enamel organ and odontogenic mesenchyme of the primitive dental pulp. Frequently diagnosed between the first and second decades of life with 75% of cases was diagnosed before the age of 20 and present with a well-defined unilocular or multilocular radiolucencies. A conservative approach, enucleation with curettage, and long-term follow-up are absolutely necessary for any recurrence or change to fibrosarcoma. We report a case of AF in a 10-year-old male patient who presented with a chief complaint of swelling in the right mandibular posterior region. Enucleation and curettage were done under general anesthesia, followed by immunohistochemical markers (Ki-67, Mib-1) to assess the sarcomatous changes and aggressiveness of the tumor.

  15. A large ameloblastic fibro-odontoma in the mandible

    PubMed Central

    Zhou, Li; Liao, Qian; Gong, Hong-Han

    2012-01-01

    Ameloblastic Fibro-Odontoma (AFO) is a rare benign hybrid odontogenic tumor. AFO is most common in children and adolescents aged under 20 years, and is usually small. This report describes a 47-year-old man with a pathologically proved large AFO originated from the mandible. The tumor’s largest dimension is 20 cm. Plain CT showed a well-circumscribed expansile mass with multiloculated scrotiform osteolytic lesions in the mandible, with linear and patchy calcification and ossification. CT 3D reconstruction revealed the mandible appeared honeycombed. On T1W and T2W MR images, cystic low-density components on CT appeared high-signal, while calcification and ossification appeared low-signal. PMID:23256073

  16. 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

  17. A Peripheral Ameloblastic Fibro-Odontoma in a 3-Year-Old Girl: Case Report, Immunohistochemical Analysis, and Literature Review

    PubMed Central

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

    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. PMID:25161776

  18. Slc26a3/Dra and Slc26a6 in Murine Ameloblasts

    PubMed Central

    Jalali, R.; Zandieh-Doulabi, B.; DenBesten, P.K.; Seidler, U.; Riederer, B.; Wedenoja, S.; Micha, D.; Bronckers, A.L.J.J.

    2015-01-01

    Formation of apatite crystals during enamel development generates protons. To sustain mineral accretion, maturation ameloblasts need to buffer these protons. The presence of cytosolic carbonic anhydrases, the basolateral Na+ bicarbonate cotransporter Nbce1, and the basolateral anion exchanger Ae2a,b in maturation ameloblasts suggests that these cells secrete bicarbonates into the forming enamel, but it is unknown by which mechanism. Solute carrier (Slc) family 26A encodes different anion exchangers that exchange Cl–/HCO3–, including Slc26a3/Dra, Slc26a6/Pat-1, and Slc26a4/pendrin. Previously, we showed that pendrin is expressed in ameloblasts but is not critical for enamel formation. In this study, we tested the hypothesis that maturation ameloblasts express Dra and Slc26a6 to secrete bicarbonate into the enamel space in exchange for Cl–. Real-time polymerase chain reaction detected mRNA transcripts for Dra and Slc26a6 in mouse incisor enamel organs, and Western blotting confirmed their translation into protein. Both isoforms were immunolocalized in ameloblasts, principally at maturation stage. Mice with null mutation of either Dra or Slc26a6 had a normal dental or skeletal phenotype without changes in mineral density, as measured by micro–computed tomography. In enamel organs of Slc26a6-null mice, Dra and pendrin protein levels were both elevated by 52% and 55%, respectively. The amount of Slc26a6 protein was unchanged in enamel organs of Ae2a,b- and Cftr-null mice but reduced in Dra-null mice by 36%. Our data show that ameloblasts express Dra, pendrin, or Slc26a6 but each of these separately is not critical for formation of dental enamel. The data suggest that in ameloblasts, Slc26a isoforms can functionally compensate for one another. PMID:26394631

  19. Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

    PubMed Central

    Houari, Sophia; Loiodice, Sophia; Jedeon, Katia; Berdal, Ariane; Babajko, Sylvie

    2016-01-01

    Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis. PMID:27853434

  20. Ameloblastic fibrodentinoma presenting as a false gingival enlargement in the maxillary anterior region.

    PubMed

    Joseph, Shiny; Priya, Lakshmi; Gopal, Dinesh; Devachen, Mary; Narayan, Ajay; Afnan, Muhammed

    2015-01-01

    Ameloblastic fibrodentinoma is a rare benign mixed odontogenic neoplasm usually occurring in the first two decades of life. It is more common in males and the most common site of occurrence is in the mandibular premolar molar area. This report presents a case of ameloblastic fibrodentinoma in a 12-year-old boy in the maxillary anterior region, a less common site for the occurrence of ameloblastic fibrodentinoma. A 12-year-old boy presented with a midline diastema in 11 and 21 region and a swelling in the palatal aspect of 11 and 12. Intraoral periapical radiograph showed the presence of rarefaction of bone on the mesial aspect of the cervical and middle third of the root of 11. Excision biopsy was done. The specimen was processed and stained with hematoxylin and eosin. Microscopic examination showed islands, chords and strands of odontogenic epithelium in a primitive ectomesenchyme resembling dental papilla. The odontogenic epithelium exhibited peripheral ameloblast-like and central stellate reticulum-like cells. The presence of dentinoid material was seen adjacent to the odontogenic epithelium in some foci. The lesion was diagnosed as ameloblastic fibrodentinoma.

  1. Ameloblastic Fibrodentinoma Presenting as a False Gingival Enlargement in the Maxillary Anterior Region

    PubMed Central

    Joseph, Shiny; Priya, Lakshmi; Gopal, Dinesh; Devachen, Mary; Narayan, Ajay; Afnan, Muhammed

    2015-01-01

    Ameloblastic fibrodentinoma is a rare benign mixed odontogenic neoplasm usually occurring in the first two decades of life. It is more common in males and the most common site of occurrence is in the mandibular premolar molar area. This report presents a case of ameloblastic fibrodentinoma in a 12-year-old boy in the maxillary anterior region, a less common site for the occurrence of ameloblastic fibrodentinoma. A 12-year-old boy presented with a midline diastema in 11 and 21 region and a swelling in the palatal aspect of 11 and 12. Intraoral periapical radiograph showed the presence of rarefaction of bone on the mesial aspect of the cervical and middle third of the root of 11. Excision biopsy was done. The specimen was processed and stained with hematoxylin and eosin. Microscopic examination showed islands, chords and strands of odontogenic epithelium in a primitive ectomesenchyme resembling dental papilla. The odontogenic epithelium exhibited peripheral ameloblast-like and central stellate reticulum-like cells. The presence of dentinoid material was seen adjacent to the odontogenic epithelium in some foci. The lesion was diagnosed as ameloblastic fibrodentinoma. PMID:25709845

  2. Ctip2/Bcl11b controls ameloblast formation during mammalian odontogenesis

    PubMed Central

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

    2009-01-01

    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. PMID:19251658

  3. 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.

  4. 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

  5. Ameloblastic fibroma or fibrosarcoma: A dilemma of oral surgeon

    PubMed Central

    Verma, Nitin; Neha

    2016-01-01

    Ameloblastic fibroma (AF) is an uncommon true mixed odontogenic tumor, with a relative frequency between 1.5% and 4.5% of all odontogenic tumors. It may behave either as a true neoplasm or as a hamartomatous proliferation of odontogenic epithelium of the enamel organ and odontogenic mesenchyme of the primitive dental pulp. Frequently diagnosed between the first and second decades of life with 75% of cases was diagnosed before the age of 20 and present with a well-defined unilocular or multilocular radiolucencies. A conservative approach, enucleation with curettage, and long-term follow-up are absolutely necessary for any recurrence or change to fibrosarcoma. We report a case of AF in a 10-year-old male patient who presented with a chief complaint of swelling in the right mandibular posterior region. Enucleation and curettage were done under general anesthesia, followed by immunohistochemical markers (Ki-67, Mib-1) to assess the sarcomatous changes and aggressiveness of the tumor. PMID:28356692

  6. Ameloblastic fibroma in an alpine chamois (Rupicapra rupicapra).

    PubMed

    Scaglione, F E; Iussich, S; Grande, D; Carpignano, M; Chiappino, L; Sereno, A; Ferroglio, E; Bollo, E

    2015-04-01

    Spontaneous odontogenic tumors are neoplasms characterized by a mixed odontogenic ectomesenchymal and odontogenic epithelial origin; they are rare in both humans and animals. A 3-year-old male Alpine Chamois (Rupicapra rupicapra) was found dead in north-west Italy, and was referred for the necropsy to the Department of Veterinary Sciences of the University of Turin (Italy). At the external examination a 10 × 8 cm, exophytic, red-pink, smooth, firm and ulcerated mass was observed on the inferior lip. Histologically the tumor was characterized by spindle shaped cells arranged in bundles in an abundant hyaline matrix. Multifocal and rare chords of odontogenic epithelium mixed with rare melanocytes that penetrate the neoplasia were visible. Immunohistochemistry showed a clear cytokeratin positivity of epithelial clusters. Macroscopical, histological and immunohistochemical findings were consistent with a diagnosis of locally infiltrative ameloblastic fibroma. To our best knowledge, this is the first report of this tumor in a wild ungulate and in Alpine Chamois. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Dental Enamel Structure Is Altered by Expression of Dominant Negative RhoA in Ameloblasts

    PubMed Central

    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 (RhoADN) in ameloblasts for in vivo analysis. Expression of the EGFP-RhoADN 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-RhoADN-8), intermediate (TgEGFP-RhoADN-2), or high (TgEGFP-RhoADN-13) levels, and the molar teeth from the 3 strains had enamel hypoplasia and surface defects. We conclude that RhoADN expressed in ameloblasts interferes with normal enamel development through the pathway that is induced by sodium fluoride. PMID:21576911

  8. 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. Copyright © 2011 S. Karger AG, Basel.

  9. Ameloblastic Fibroodontoma of the Mandible with Normal Karyotype in a Pediatric Patient

    PubMed Central

    Manor, Esther; Kan, Elena; Bodner, Lipa

    2012-01-01

    Background. Ameloblastic fibroodontoma (AFO) is a rare mixed odontogenic tumor with epithelial and mesenchymal components. AFO presents as a painless swelling in the mandible or maxilla. Radiographs show a well-defined radiolucent area containing various amounts of radiopaque material of irregular size and form. The common treatment is enucleation. It is not an aggressive tumor but recurrence and malignant transformation are possible. Methods. An AFO of the mandible of a 3-year-old female is reported. Panoramic radiograph and CT scan revealed a unilocular lesion with radiopaque center and radiolucent margins. Enucleation was performed with a good outcome. Results. Histopathology was a classic AFO. The karyotype was normal. No recurrence was noted at 12 months. Conclusions. As it is a benign tumor with low recurrence rate, conservative surgery is the treatment of choice. As malignant transformation to ameloblastic fibrosarcoma or ameloblastic odontosarcoma is possible despite the normal karyotype, long-term followup is recommended. PMID:22924135

  10. 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. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. Ameloblastic fibrosarcoma of the mandible: report of 2 chemosensitive pediatric cases.

    PubMed

    Demoor-Goldschmidt, Charlotte; Minard-Colin, Veronique; Cassagneau, Elizabeth; Supiot, Stephane; Oberlin, Odile; D'hautuille, Cedric; Corradini, Nadege

    2012-03-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor. We report 2 pediatric cases of AFS from 2 different centers but reviewed by the same pathologist, which were unusual in that they were chemosensitive. Management was wide surgical resection, chemotherapy, and adjuvant radiotherapy. One case was a local AFS recurrence after incomplete surgery and the other was an AFS that was overlooked during earlier diagnosis of an ameloblastic fibroma. Both tumors responded very well to preoperative chemotherapy, with a reduction in tumor size and histologically proven decrease in viable tumor cell number. Both patients are well after 13 and 14 months of follow-up.

  12. 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.

  13. Ameloblastic fibro-odontoma: expansile mixed radiolucent lesion in the posterior maxilla: a case report.

    PubMed

    Zouhary, Kenneth J; Said-Al-Naief, Nasser; Waite, Peter D

    2008-10-01

    Ameloblastic fibro-odontoma (AFO) is a benign tumor that displays properties of both ameloblastic fibroma and compound odontoma. Often, AFO presents clinically as a hamartoma or immature odontoma; however, the tumor can also present with progressive growth causing bone destruction and significant deformity, acting more like a true neoplasm. We report a case of a locally aggressive AFO in the posterior maxilla of a 7-year-old girl and discuss the clinical, radiographic, histopathologic, and conservative therapeutic approach to this locally aggressive tumor.

  14. 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.

  15. Ameloblastic fibroodontoma or complex odontoma: Two faces of the same coin

    PubMed Central

    Singh, Akhilesh Kumar; Kar, Indu Bhusan; Mishra, Niranjan; Sharma, Parikshit

    2016-01-01

    An ameloblastic fibroodontoma (AFO) is a rare odontogenic tumor of mixed dental tissue origin. It exhibits histological features of ameloblastic fibroma and complex odontoma. AFOs are usually found to be asymptomatic and are most often discovered on routine radiography. Sometimes their presence is suspected due to missing permanent dentition. We report a case of an 18-year-old female patient with missing mandibular molars on the left side associated with a giant complex odontoma. Treatment included surgical excision of the tumor followed by reconstruction with iliac crest graft. Histopathological study revealed it as an AFO, to our surprise. PMID:28163488

  16. [A case reported of an ameloblastic fibroma in which involved three right molars in a teenager].

    PubMed

    Ruiz-Ortega, Susana; Tovar-Bernal, Cuauhtémoc; Soriano-Padilla, Fernando

    2011-01-01

    Ameloblastic fibroma is a benign tumor of mixed odontogenic origin, which occurs in ages from 12 to 15 years, frequently in the molar area. Generally it is asymptomatic, however the biggest lesions can be associated to pain and swelling. Using X-ray they appear well defined, transparent, with a sclerotic radio-opaque border; occasionally they can simulate a dentigerous cyst. The treatment is generally conservative. This report describes an ameloblastic fibroma in a 14-year-old male, which involved the three right molars and both the ascending ramous and the coronoid process, which was treated conservatively with the extraction of the affected teeth, tumor extirpation and osseous curettage.

  17. Ameloblastic fibroodontoma or complex odontoma: Two faces of the same coin.

    PubMed

    Singh, Akhilesh Kumar; Kar, Indu Bhusan; Mishra, Niranjan; Sharma, Parikshit

    2016-01-01

    An ameloblastic fibroodontoma (AFO) is a rare odontogenic tumor of mixed dental tissue origin. It exhibits histological features of ameloblastic fibroma and complex odontoma. AFOs are usually found to be asymptomatic and are most often discovered on routine radiography. Sometimes their presence is suspected due to missing permanent dentition. We report a case of an 18-year-old female patient with missing mandibular molars on the left side associated with a giant complex odontoma. Treatment included surgical excision of the tumor followed by reconstruction with iliac crest graft. Histopathological study revealed it as an AFO, to our surprise.

  18. Laryngeal Verrucous Carcinoma: A Population-Based Analysis.

    PubMed

    Dubal, Pariket M; Svider, Peter F; Kam, David; Dutta, Rahul; Baredes, Soly; Eloy, Jean Anderson

    2015-11-01

    Verrucous carcinoma of the larynx (VCL) is a rare entity with reportedly favorable prognosis. Current analyses are limited primarily to case reports and case series, thus making a population-based analysis useful in characterizing frequency, incidence, and survival trends to guide clinical diagnosis and decision making. Analysis of the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) database. Cases of VCL diagnosed between 1973 and 2011 were searched in the SEER database. Analysis was carried out with respect to patient demographics, tumor characteristics, incidence, treatment modality, and survival. In sum, 516 patients with VCL were identified. Males composed 88.4% of cases. Whites accounted for 88.4% of cases, with 8.1% of cases occurring in black patients. Most cases (79.7%) arose in the glottis, a statistically significant predilection when compared with other laryngeal malignancies (P < .0001). Incidence of VCL decreased from 2000 to 2011, with an annual percent change of -5.4%. Overall 1-, 5-, and 10-year disease-specific survival for VCL was 97.5%, 88.0%, and 77.4%, while 1-, 5-, and 10-year relative survival was 98.1%, 85.5%, and 74.2%, respectively. Surgery seemed to confer better prognosis when compared with other treatment modalities. This large population-based analysis of VCL demonstrates that this entity has a good prognosis, arises in the glottis, and is decreasing in incidence. Five-year survival seems highest when surgery is utilized. However, this finding may be subject to selection bias in high-stage lesions. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  19. Locally infiltrative ameloblastic fibroma in a rhesus macaque (Macaca mulatta) with characterizations of its proliferating activity and biological behavior.

    PubMed

    Liu, David X; Doyle, Lara A; Bouljihad, Mostafa T; Didier, Peter J; Gilbert, Margaret H; Wang, Xiaolei; Pahar, Bapi; Bohm, Rudolf P; Veazey, Ronald S; Lackner, Andrew A

    2012-05-01

    An 8-year-old male rhesus macaque (Macaca mulatta) presented with unilateral enlargement of the left mandible. Radiographs revealed a marked expansion of the left mandible with a multilocular radiolucent mass with abundant osteolysis. The mass was grossly firm, fleshy, and gelatinous on the cut surface. Histologically, the mass was locally infiltrative and composed of neoplastic epithelial and mesenchymal components that stained positive for cytokeratin and vimentin, respectively. Occasional densely spherical condensations of fibroblasts resembling the cap stage of odontogenesis were present in the mesenchyma. Immunohistochemical staining with Ki-67, S-100, and CD34 indicated that both epithelial and mesenchymal components of the neoplasm had low proliferation. Alcian blue, periodic acid-Schiff, and trichrome stains showed an immature stromal component with no collagen formation. Based on the clinical, histologic, and immunophenotypic features, the tumor was identified as a locally infiltrative ameloblastic fibroma.

  20. Locally infiltrative ameloblastic fibroma in a rhesus macaque (Macaca mulatta) with characterizations of its proliferating activity and biological behavior

    PubMed Central

    Liu, David X.; Doyle, Lara A.; Bouljihad, Mostafa T.; Didier, Peter J.; Gilbert, Margaret H.; Wang, Xiaolei; Pahar, Bapi; Bohm, Rudolf P.; Veazey, Ronald S.; Lackner, Andrew A.

    2014-01-01

    An 8-year-old male rhesus macaque (Macaca mulatta) presented with unilateral enlargement of the left mandible. Radiographs revealed a marked expansion of the left mandible with a multilocular radiolucent mass with abundant osteolysis. The mass was grossly firm, fleshy, and gelatinous on the cut surface. Histologically, the mass was locally infiltrative and composed of neoplastic epithelial and mesenchymal components that stained positive for cytokeratin and vimentin, respectively. Occasional densely spherical condensations of fibroblasts resembling the cap stage of odontogenesis were present in the mesenchyma. Immunohistochemical staining with Ki-67, S-100, and CD34 indicated that both epithelial and mesenchymal components of the neoplasm had low proliferation. Alcian blue, periodic acid–Schiff, and trichrome stains showed an immature stromal component with no collagen formation. Based on the clinical, histologic, and immunophenotypic features, the tumor was identified as a locally infiltrative ameloblastic fibroma. PMID:22529141

  1. Mining featured biomarkers associated with prostatic carcinoma based on bioinformatics.

    PubMed

    Piao, Guanying; Wu, Jiarui

    2013-11-01

    To analyze the differentially expressed genes and identify featured biomarkers from prostatic carcinoma. The software "Significance Analysis of Microarray" (SAM) was used to identify the differentially coexpressed genes (DCGs). The DCGs existed in two datasets were analyzed by GO (Gene Ontology) functional annotation. A total of 389 DCGs were obtained. By GO analysis, we found these DCGs were closely related with the acinus development, TGF-β receptor and signal transduction pathways. Furthermore, five featured biomarkers were discovered by interaction analysis. These important signal pathways and oncogenes may provide potential therapeutic targets for prostatic carcinoma.

  2. Medullary carcinoma of the large intestine: a population based analysis.

    PubMed

    Thirunavukarasu, Pragatheeshwar; Sathaiah, Magesh; Singla, Smit; Sukumar, Shyam; Karunamurthy, Arivarasan; Pragatheeshwar, Kothai Divya; Lee, Kenneth K W; Zeh, Herbert; Kane, Kevin M; Bartlett, David L

    2010-10-01

    Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.

  3. 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.

  4. A Vector-Based Short Hairpin RNA Targeting Aurora B Suppresses Human Prostatic Carcinoma Growth.

    PubMed

    Cao, Mei; Qi, Panpan; Chen, Chong; Song, Liju; Wang, Xuege; Li, Ningzhe; Wu, Daoyan; Hu, Guoku; Zhao, Jian

    2017-02-01

    Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot. At the same time, cell apoptosis was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, fluorescent staining, and flow cytometric analysis. Furthermore, prostate carcinoma cells were injected into mice to establish a tumor xenograft model. Previous studies have shown the effect of pGPU6-shAURKB plasmid on tumor growth in a prostate carcinoma xenogenic implantation model. From the study, we knew that the Aurora kinase B was significantly downregulated in prostate carcinoma cells, and cell apoptosis was also detected higher in treated groups than that in control groups. Moreover, in the prostate carcinoma xenogenic implantation model, compared with the control groups, the tumor growth was inhibited about 78.7% in the pGPU6-shAURKB plasmid-treated group, and cell apoptosis in the experimental group was notably higher than that in control groups. The average duration of tumor-bearing mice was prolonged to about 35 days. The results of experiment indicated that specific knockdown of Aurora kinase B led to prostate carcinoma cells apoptosis and inhibited tumor growth. Our data clearly confirmed that specific knockdown of Aurora kinase B expression by vector-based short hairpin RNA/liposome may be a potential new approach to treat human prostatic carcinoma.

  5. 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

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

    PubMed

    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.

  7. Ameloblastic Fibro-odontome (AFO) of the Mandible: A Case Report.

    PubMed

    G, Sreenath; Reddy Y, Indira; P, Sreenivasreddy; Prakash A, Ravi

    2014-01-01

    Odontoameloblastoma are tumours which represent a histological combination of ameloblastoma and complex odontoma. It behaves in an invasive manner like Ameloblastoma and is more aggressive in nature. We report a new case of ameloblastic fibro-odontoma (AFO). Clinical, radiographic and histopathological features are discussed.

  8. So-called "immature dentinoma": a case presentation and histological comparison with ameloblastic fibrodentinoma.

    PubMed

    Takeda, Y

    1994-02-01

    The existence of the "dentinoma" as an independent entity has not been fully accepted, recently being regarded as an ameloblastic fibroma with formation of dentin and named an ameloblastic fibrodentinoma. However, there are histological differences between the several cases reported previously as "immature dentinoma" and the ameloblastic fibrodentinoma. This paper presents a case report of a dentin-forming intraosseous benign tumor without any histological features of ameloblastic fibroma. The patient was a 30-year-old woman with a rather well-circumscribed intraosseous lesion of the mandibular left premolar area. Histologically, the lesion consisted of dentin-like tissue with a tubular structure and globular calcifications, numerous epithelial strands and islands without enamel organ-like structure, and a cellular fibrous component without a primitive dental papilla-like appearance. The present case and a review of the literature suggest that epithelial elements in odontogenic fibroma-like lesions may occasionally have an inductive effect for dentin or dentin-like tissue formation.

  9. 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

  10. Ionizing radiation effects on the secretory-stage ameloblasts and enamel organic extracellular matrix.

    PubMed

    de Moraes Ramos-Perez, Flávia Maria; do Espírito Santo, Alexandre Ribeiro; da Cruz Perez, Danyel Elias; Novaes, Pedro Duarte; Bóscolo, Frab Norberto; Line, Sérgio Roberto Peres; de Almeida, Solange Maria

    2014-08-01

    This study assessed the effects of high doses of ionizing radiation on eruption rate, odontogenic region morphology, secretory-stage ameloblasts, and enamel organic extracellular matrix (EOECM) of rat maxillary incisors. For the study, 30 male rats were divided into three experimental groups: control (non-irradiated), irradiated by 15 Gy, and irradiated by 25 Gy. Irradiated groups received a single dose of 15 or 25 Gy of X-rays in the head and neck region. The maxillary incisor eruption rate was measured. Sections of 5-µm thickness of the maxillary incisor odontogenic regions were evaluated using bright field light microscopy. Ultrathin sections of secretory ameloblasts and their EOECM were analyzed by transmission electron microscopy (TEM). Irradiated groups showed significantly diminished eruption rate values at the 4th and at the 6th day after irradiation. Reduced optical retardation values were observed in the irradiated groups. The odontogenic region of maxillary incisors from irradiated rats exhibited altered and poorly organized preameloblasts. TEM showed degeneration areas in the secretory-stage EOECM and several autophagosomes in the secretory ameloblasts from irradiated animals. In conclusion, high radiation doses delay eruption and induce disturbances in secretory ameloblasts and EOECM of rat maxillary incisors. These findings may be associated with structural defects of mature enamel.

  11. {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.

  12. Population based cancer registry analysis of primary tracheal carcinoma.

    PubMed

    Urdaneta, Alfredo I; Yu, James B; Wilson, Lynn D

    2011-02-01

    Primary carcinomas of the trachea are rare tumors, occurring at a rate of 2.6 new cases per 1,000,000 people per year. This study investigates the large observational cohort of patients recorded in the NCI Surveillance, Epidemiology, and End Results (SEER) 1973-2004 database, and provides information regarding epidemiology, treatment, and prognosis. The SEER database was investigated, and all patients for whom primary tracheal carcinoma was the first and only cancer were investigated. Demographic information was investigated. The cohort was analyzed for variables effecting survival, including age, gender, race, histology, extent of disease, extent of surgery, use of radiation, and year of diagnosis. Between 1973 and 2004, 578 cases of primary tracheal carcinomas were reported in the SEER database. There were 322 men (55.7%) and 256 women (44.3%). Squamous cell carcinoma was the predominant histology, representing 259 tumors (44.8%). Adenoid cystic carcinoma (ACC) was the second most common tumor (16.3%). Localized, regional and distant disease was found in 140 (24.2%), 212 (36.7%), and 108 (18.7%), respectively. Twenty percent of the patients did not undergo staging. Patients with localized disease had a better prognosis than those with regional (P = 0.001) or distant disease (P = <0.001).A significant fraction of patients did not receive cancer directed local therapy; 34.3% did not undergo surgery and 29.1% did not receive any kind of radiation therapy. There was a statistically significant improved survival for patients who underwent any type of surgery in comparison with patients who did not undergo cancer directed surgery. There was no statistical benefit for patients who underwent radiation therapy.General overall 5-year survival for all patients was 27.1% (95% CI: 23.1-33.3%). Patients with localized disease had a better outcome than patients with regional or distant disease with an overall 5-year survival of 46% (95% CI: 37.3%-55.8%). Squamous cell carcinoma

  13. Basal cell carcinoma: an evidence-based treatment update.

    PubMed

    Clark, Charlotte M; Furniss, Megan; Mackay-Wiggan, Julian M

    2014-07-01

    Basal cell carcinoma (BCC) is the most common skin cancer. Surgical excision remains the standard of treatment, but several alternative treatment modalities exist. This review aims to provide a current analysis of evidence for the treatment of BCC; specifically, which treatments have the lowest recurrence rates and the best cosmetic outcomes. We searched PubMed (January 1946 to August 2013), Ovid MEDLINE (2003-August 2013), the Cochrane Central Register of Controlled Trials (January 1993 to August 2013), and the Cochrane Database of Systematic Reviews (The Cochrane Library Issue 9, 2013) databases for randomized controlled trials, systematic reviews, or comparative studies for the treatment of BCC. We found 615 potential articles. Two independent reviewers selected 40 studies: 29 randomized controlled trials (RCTs), seven systematic reviews, and four nonrandomized prospective trials. Treatment modalities reviewed include surgical therapy, radiotherapy and cryotherapy, photodynamic therapy (PDT), topical imiquimod, topical 5-fluorouracil (5-FU), topical solasodine glycoalkaloids, topical ingenol mebutate, intralesional 5-FU, intralesional interferon (IFN), and oral hedgehog pathway inhibitors. The available data suggest that surgical methods remain the gold standard in BCC treatment, with Mohs micrographic surgery typically utilized for high-risk lesions. Suitable alternate treatment options for appropriately selected primary low-risk lesions may include PDT, cryotherapy, topical imiquimod, and 5-FU. Radiotherapy is a suitable alternate for surgical methods for treatment in older patient populations. Electrodesiccation and curettage (ED&C) is a commonly used primary treatment option for low-risk lesions; however, there were no RCTs examining ED&C that met our inclusion criteria. New hedgehog pathway inhibitors are promising for the management of advanced BCC; however, side effects are a concern for some patients, and much remains to be learned regarding optimal

  14. 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.

  15. Ameloblastic Fibroodontoma: Uncommon Case Presentation in a 6-Year-Old Child with Review of the Literature

    PubMed Central

    Abdulla, Anshad Mohamed; Surej Kumar, L. K.; Sheejith Hari Peeceeyen, C. S.

    2017-01-01

    Ameloblastic fibroodontoma is a benign mixed odontogenic neoplasm considered in patients with asymptomatic swelling and unerupted teeth that exhibit histologic features between ameloblastic fibroma and complex odontoma. Radiographically, this lesion appears as radiolucency admixed with focal radio opaque masses of irregular shapes and sizes. This lesion is confirmed by the presence of proliferating odontogenic epithelium, ectomesenchyme, and dental hard tissue formation on pathological analysis supplementing clinical and radiographic findings. As this tumour is less commonly seen in routine clinical practice, ameloblastic fibroodontoma with detailed orofacial features and periodic approach to its diagnosis is discussed. This paper reports a case of ameloblastic fibroodontoma of the mandible in a 6-year-old male patient with an uncommon case presentation and review of the literature.

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

    PubMed Central

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

    2015-01-01

    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 HPO42– (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 Ca2+, 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 reduce the transport

  17. Rapid sarcomatous transformation of an ameloblastic fibroma of the mandible: case report and literature review.

    PubMed

    Kousar, Aisha; Hosein, Mervyn M; Ahmed, Zubair; Minhas, Khurram

    2009-09-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumour regarded as the malignant counterpart of ameloblastic fibroma. It is characterized by a benign epithelial component within a malignant fibrous stroma. AFS is a locally aggressive neoplasm with extremely low potential for metastasis. We report an extremely rare, rapidly progressive, and fatal case originating in the posterior mandible of a 20-year old female patient. Initially histopathologically diagnosed as a benign lesion, it rapidly recurred with apparent transformation into a high-grade sarcoma over a period of 6 months. Subsequent intracranial and pulmonary metastases were noted, and the patient died within 15 months of initial consultation. This case emphasizes the need for a high element of suspicion about clinically ambiguous lesions. We recommend more extensive or radical, primary excisions in lesions that have a known potential for recurrence or malignancy.

  18. Ameloblastic fibroma: a rare case report with 7-year follow-up.

    PubMed

    Melo, Leonardo de Araújo; Barros, Adna Conceição; Sardinha, Sandra de Cássia Santana; Cerqueira, Arlei; dos Santos, Jean Nunes

    2015-01-01

    Ameloblastic fibroma (AF) is a rare benign odontogenic tumor that usually occurs in the fi two decades of life. It affects adolescents and young adults and is found in the mandible and with a high frequency in the posterior region of this segment. There are rare case reports with a long-term follow-up. We report the case of a 6-year-old boy with extensive ameloblastic fibroma in the man ble. Treatment consisted of enucleation and bone curettage, with the preservation of permanent teE adjacent to the tumor. Clinical and radiographic follow-up of the patient over a period of 7 years show no signs of recurrence or malignant transformation. Patients with AF should be under follow-up for prolonged periods of time, even in ca! exhibiting a low proliferation index, because of the potential for recurrence and malignant transformation of this tumor.

  19. Ameloblastic fibrosarcoma of the mandible: A case report and mini review

    PubMed Central

    HU, YUAN-YUAN; DENG, MO-HONG; YUAN, LING-LING; NIU, YU-MING

    2014-01-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic neoplasm of the jaw. AFS is characteristically composed of a benign odontogenic epithelium and a malignant mesenchymal component. The posterior region of the mandible is the predominantly occupied site. In the present report, a new case of AFS in a 22-year-old male that originated from ameloblastic fibroma was described. Histologically, the tumor showed biphasic components: Benign epithelium and a malignant mesenchymal component. Immunochemical findings revealed that the tumor cells were positive for cluster of differentiation (CD) 34, vimentin, Ki-67 and p53, but negative for smooth muscle actin, S-100, CD68 and desmin. The clinical presentation, radiographic appearances and treatment measures were additionally described and reviewed. PMID:25289041

  20. Ameloblastic fibrosarcoma of the mandible: A case report and mini review.

    PubMed

    Hu, Yuan-Yuan; Deng, Mo-Hong; Yuan, Ling-Ling; Niu, Yu-Ming

    2014-11-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic neoplasm of the jaw. AFS is characteristically composed of a benign odontogenic epithelium and a malignant mesenchymal component. The posterior region of the mandible is the predominantly occupied site. In the present report, a new case of AFS in a 22-year-old male that originated from ameloblastic fibroma was described. Histologically, the tumor showed biphasic components: Benign epithelium and a malignant mesenchymal component. Immunochemical findings revealed that the tumor cells were positive for cluster of differentiation (CD) 34, vimentin, Ki-67 and p53, but negative for smooth muscle actin, S-100, CD68 and desmin. The clinical presentation, radiographic appearances and treatment measures were additionally described and reviewed.

  1. Mandibular ameloblastic fibroma in 6-years-old girl: a case report.

    PubMed

    Anesi, A; Albanese, M; Gerosa, R; Corrocher, G; Gambarini, G; Nocini, P F

    2008-10-01

    Ameloblastic fibroma (AF) is defined in WHO classification as a ''neoplasm composed of proliferating odontogenic epithelium embedded in a cellular ectomesenchymal tissue that resembles dental papilla, and with varying degrees of inductive change and dental hard tissue formation''. AF is a rather uncommon tumor, accounting for only 2.5% of all odontogenic tumors. AF is a true mixed tumor, in which the epithelial and ectomesenchymal elements are neoplastic. AF raises at any age, ranging from 6 months to 42 years (mean 14.6 to 15.5 years); it does not show sex predilection. The lesion occurs in nearly 70% of cases in posterior areas of the mandible. Patients exhibit swelling of the jaw; pain is not usually described. Authors present a clinical and surgical management of an early onset of a large mandibular ameloblastic fibroma in a 6-year-old girsl.

  2. Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Li, Lianhuang; Jiang, Weizhong; Yang, Yinghong; Chen, Zhifen; Feng, Changyin; Li, Hongsheng; Guan, Guoxian; Chen, Jianxin

    2014-06-01

    Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.

  3. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    PubMed

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  4. 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.

  5. Ameloblastic fibroma in six-year-old male: Hamartoma or a true neoplasm.

    PubMed

    Jindal, Chhavi; Bhola, Reena Sarkar

    2011-09-01

    Ameloblastic fibroma (AF) is an uncommon true mixed odontogenic tumor with a relative frequency between 1.5% and 4.5%. Recently, it has been proposed that two subtypes of AF exist: A neoplasm and a hamartomatous lesion. We report a case of AF in left mandibular posterior region in a 6-year-old male patient. The tumor showed unusual and aggressive features that suggested it was a true neoplasm.

  6. Ameloblastic fibroma in six–year-old male: Hamartoma or a true neoplasm

    PubMed Central

    Jindal, Chhavi; Bhola, Reena Sarkar

    2011-01-01

    Ameloblastic fibroma (AF) is an uncommon true mixed odontogenic tumor with a relative frequency between 1.5% and 4.5%. Recently, it has been proposed that two subtypes of AF exist: A neoplasm and a hamartomatous lesion. We report a case of AF in left mandibular posterior region in a 6-year-old male patient. The tumor showed unusual and aggressive features that suggested it was a true neoplasm. PMID:22144834

  7. Expression of the Sodium/Calcium/Potassium Exchanger, NCKX4, in Ameloblasts

    PubMed Central

    Hu, Ping; Lacruz, Rodrigo S.; Smith, Charles E.; Smith, Susan M.; Kurtz, Ira; Paine, Michael L.

    2012-01-01

    Transcellular calcium transport is an essential activity in mineralized tissue formation, including dental hard tissues. In many organ systems, this activity is regulated by membrane-bound sodium/calcium (Na+/Ca2+) exchangers, which include the NCX and NCKX [sodium/calcium-potassium (Na+/Ca2+-K+ ) exchanger] proteins. During enamel maturation, when crystals expand in thickness, Ca2+ requirements vastly increase but exactly how Ca2+ traffics through ameloblasts remains uncertain. Previous studies have shown that several NCX proteins are expressed in ameloblasts, although no significant shifts in expression were observed during maturation which pointed to the possible identification of other Ca2+ membrane transporters. NCKX proteins are encoded by members of the solute carrier gene family, Slc24a, which include 6 different proteins (NCKX1–6). NCKX are bidirectional electrogenic transporters regulating Ca2+ transport in and out of cells dependent on the transmembrane ion gradient. In this study we show that all NCKX mRNAs are expressed in dental tissues. Real-time PCR indicates that of all the members of the NCKX group, NCKX4 is the most highly expressed gene transcript during the late stages of amelogenesis. In situ hybridization and immunolocalization analyses clearly establish that in the enamel organ, NCKX4 is expressed primarily by ameloblasts during the maturation stage. Further, during the mid-late maturation stages of amelogenesis, the expression of NCKX4 in ameloblasts is most prominent at the apical poles and at the lateral membranes proximal to the apical ends. These data suggest that NCKX4 might be an important regulator of Ca2+ transport during amelogenesis. PMID:22677781

  8. Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation.

    PubMed

    Kubota, Kaori; Lee, Daniel H; Tsuchiya, Masahiro; Young, Conan S; Everett, Eric T; Martinez-Mier, Esperanza A; Snead, Malcolm L; Nguyen, Linh; Urano, Fumihiko; Bartlett, John D

    2005-06-17

    The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.

  9. Omics-Based Identification of Biomarkers for Nasopharyngeal Carcinoma

    PubMed Central

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is highly found in distinct geographic areas, such as Southeast Asia. The management of NPC remains burdensome as the prognosis is poor due to the late presentation of the disease and the complex nature of NPC pathogenesis. Therefore, it is necessary to find effective molecular markers for early detection and therapeutic measure of NPC. In this paper, the discovery of molecular biomarker for NPC through the emerging omics technologies including genomics, miRNA-omics, transcriptomics, proteomics, and metabolomics will be extensively reviewed. These markers have been shown to play roles in various cellular pathways in NPC progression. The knowledge on their function will help us understand in more detail the complexity in tumor biology, leading to the better strategies for early detection, outcome prediction, detection of disease recurrence, and therapeutic approach. PMID:25999660

  10. Effects of sodium fluoride on the actin cytoskeleton of murine ameloblasts.

    PubMed

    Li, Yong; Decker, Sylvia; Yuan, Zhi-An; Denbesten, Pamela K; Aragon, Melissa A; Jordan-Sciutto, Kelly; Abrams, William R; Huh, Jung; McDonald, Celeste; Chen, Enhong; MacDougall, Mary; Gibson, Carolyn W

    2005-08-01

    Fluoride is associated with a decrease in the incidence of dental caries, but excess fluoride can lead to enamel fluorosis, a defect that occurs during tooth enamel formation. In fibroblasts, the Arhgap gene encodes a RhoGAP, which regulates the small G protein designated RhoA. Fluoride treatment of fibroblasts inactivates RhoGAP, thereby activating RhoA, which leads to elevation of filamentous actin (F-actin). Since RhoA is a molecular switch, our hypothesis is that in ameloblasts, fluoride may alter the cytoskeleton through interference with the Rho signaling pathway. Our objective was to measure the effects of sodium fluoride on F-actin using tooth organ culture and confocal microscopy. The results indicated that cellular responses to fluoride include elevation of F-actin in ameloblasts. It was concluded from immunohistochemistry, RT-PCR and confocal approaches that the components of the Rho pathway are present in ameloblasts, and that the response to fluoride involves the Rho/ROCK pathway.

  11. 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

  12. Store-operated Ca2+ entry controls ameloblast cell function and enamel development

    PubMed Central

    Eckstein, Miriam; Vaeth, Martin; Fornai, Cinzia; Vinu, Manikandan; Bromage, Timothy G.; Nurbaeva, Meerim K.; Sorge, Jessica L.; Coelho, Paulo G.; Idaghdour, Youssef; Feske, Stefan; Lacruz, Rodrigo S.

    2017-01-01

    Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca2+ release–activated Ca2+ (CRAC) channels and store-operated Ca2+ entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2K14cre mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2K14cre mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2K14cre mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel. PMID:28352661

  13. 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

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

    PubMed

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

    2016-04-01

    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. 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. Although AFO is a rare tumor, it is more prevalent in children's jaw. Conservative surgical treatment allowed the normal development of teeth.

  15. Cytochemical studies of ameloblasts and the surface layer of enamel of the rat incisor at the maturation stage.

    PubMed

    Takano, Y

    1979-01-01

    In order to elucidate the cytochemical properties of the membranous structure between enamel and ameloblasts of the rat incisor at the maturation stage, chromic phosphotungstic acid (Cr-PTA) and periodic acid-silver methenamine (PA-silver) techniques for electron microscopy were employed in combination with a digestion test with hyaluronidase, neuraminidase, collagenase or trypsin. Also, acid phosphatase activity of ameloblasts at the maturation stage was examined with a modified GOMORI's metal salt method. An intensely Cr-PTA reactive band approximately 0.1 micron thick appeared along the surface layer of enamel at the transitional stage, and at the very beginning of the maturation stage another intensely Cr-PTA reactive band which was seen by uran-lead stain to be a delicate electron-dense membranous structure appeared as well between enamel and ameloblasts. A lot of cytoplasmic small vesicles or tubular structures, both intensely reactive to Cr-PTA, were observed near the apical membranes of the overlying ameloblasts indicating that those organelles must have been responsible for the secretion of the latter band. Acid phosphatase activity was clearly demonstrated at Cr-PTA reactive large vesicles in the cytoplasm of those cells. The PA-silver staining technique manifested a band heavily deposited with silver grains along the surface layer of enamel, i.e., where the former band existed, but showed no particular reaction at the latter, the band-like layer between enamel and ameloblasts. Hyaluronidase or neuraminidase treatment remarkably decreased the Cr-PTA reaction of the latter band. Trypsin or collagenase treatment, on the other hand, not only eliminated the Cr-PTA reaction but digested the band itself. These results suggest that the membranous structure between enamel and ameloblasts of a rat incisor is not so-called enamel cuticle but a basal lamina produced by overlying ameloblasts and that the basal lamina contains collagenous components even though it

  16. Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways.

    PubMed

    Li, Weishan; Jiang, Binghua; Cao, Xianglin; Xie, Yongjiang; Huang, Ting

    2017-01-05

    Fluoride is an environmental toxicant and induces dental fluorosis and oxidative stress. Lycopene (LYC) is an effective antioxidant that is reported to attenuate fluoride toxicity. To determine the effects of LYC on sodium fluoride (NaF) -induced teeth and ameloblasts toxicity, rats were treated with NaF (10 mg/kg) and/or LYC (10 mg/kg) by orally administration for 5 weeks; ameloblasts were treated with NaF (5 mM) and/or LYC (2 μM) for 6 h. We found that the concentrations of fluoride, malondialdehyde (MDA) and reactive oxygen species (ROS), gene expressions and activities of Caspase-9 and Caspase-3, and the gene expressions of Bax were significantly decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX), the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated rats group; concentrations of MDA and ROS, gene expressions and activities of Caspase-9 and Caspase-3, and the gene expression of Bax, and ameloblasts apoptosis rate were significantly decreased, while the activities of SOD and GPX, the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated ameloblasts group. These results suggest that LYC significantly combated NaF-induced ameloblasts apoptosis and dental fluorosis by attenuation oxidative stress and down-regulation Caspase pathway.

  17. ERBB4 Expression in Ovarian Serous Carcinoma Resistant to Platinum-Based Therapy.

    PubMed

    Saglam, Ozlen; Xiong, Yin; Marchion, Douglas C; Strosberg, Carolina; Wenham, Robert M; Johnson, Joseph J; Saeed-Vafa, Daryoush; Cubitt, Christopher; Hakam, Ardeshir; Magliocco, Anthony M

    2017-01-01

    Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories. Category frequencies were compared between tumor specimens vs controls using an unpaired t test. Among tumors, category frequencies were compared between CR and IR to chemotherapy. Overall survival (OS) was stratified by category. In total, 74 ovarian serous carcinoma samples (32 CRs and 42 IRs), 28 normal controls, and 16 ovarian cancer cell lines were evaluable. High-level ERBB4 expression was observed at a significantly higher frequency in ovarian serous carcinoma compared with normal control tissue. Among tumor specimens, ERBB4 expression was significantly higher for those with an IR to chemotherapy compared with CR (P = .033). OS was inversely correlated with ERBB4 expression levels. Median rates of OS were 18, 22, and 58 months among high-, intermediate-, and low-expression tumors, respectively. Our results indicate that ERBB4 expression by immunohistochemistry may correlate with chemotherapy-resistant ovarian serous carcinoma and shortened OS.

  18. Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

    PubMed

    Trapasso, Francesco; Sarti, Manuela; Cesari, Rossano; Yendamuri, Sai; Dumon, Kristoffel R; Aqeilan, Rami I; Pentimalli, Francesca; Infante, Luisa; Alder, Hansjuerg; Abe, Nobutsugu; Watanabe, Takashi; Viglietto, Giuseppe; Croce, Carlo M; Fusco, Alfredo

    2004-09-01

    Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

  19. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  20. Effects of a macrolide antibiotic on enamel formation in rat incisors--primary lesion of ameloblast at the transition stage.

    PubMed

    Abe, Toshio; Miyajima, Hiroaki; Okada, Kosuke

    2003-09-01

    A novel macrolide antibiotic was administered orally to 5-week-old Jcl:Wistar rats at a dose of 5,000 mg/kg/day for 5 weeks, and then a half of animals were maintained without any treatment for 10 weeks. A white discolored lesion with horizontal stripes developed on the surface of the upper and lower incisors after dosing for 4 weeks, and these macroscopical incisal lesions disappeared with the eruption in 4 weeks after stop of administration. Histopathologically, increase in number of karyopycnosis of ameloblast at the transitional stage, vacuolar degeneration of ameloblast and cystic change in the maturation stage, and impaired iron pigment secretion at the pigmentation stage were observed. Microradiography, calcio-traumatic zones, which means hypocalcification, were observed on the superficial layer of enamel. These results suggest that the primary lesion induced by a novel macrolide antibiotic is the increased karyopycnosis of ameloblast at the transitional stage, and followed by later stage.

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

    PubMed

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

    2016-09-01

    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.

  2. 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

  3. Ameloblastic Fibroma of the Maxilla with Bilateral Presentation: Report of a Rare Case with Review of the Literature

    PubMed Central

    Ealla, Kranti Kiran Reddy; Basavanapalli, Vijayabaskar Reddy; Velidandla, Surekha Reddy; Manikya, Sangameshwar; Ragulakollu, Rajesh; Danappanavar, Prasanna M.; Vennila, Vijayasree

    2015-01-01

    Ameloblastic fibroma (AF) is an uncommon benign odontogenic tumour, with both epithelial and mesenchymal neoplastic proliferation. It occurs most frequently in the posterior region of the mandible, while its occurrence in the maxilla is extremely rare. They are usually encountered in children, emphasizing it as an important diagnostic consideration. Herein, we report the first case of a bilateral maxillary ameloblastic fibroma in a 2-year-old female child patient who presented with a chief complaint of swelling in the right mid facial region. PMID:25628911

  4. 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. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  5. Ameloblastic fibroma of the maxilla with bilateral presentation: report of a rare case with review of the literature.

    PubMed

    Ealla, Kranti Kiran Reddy; Basavanapalli, Vijayabaskar Reddy; Velidandla, Surekha Reddy; Manikya, Sangameshwar; Ragulakollu, Rajesh; Danappanavar, Prasanna M; Vennila, Vijayasree

    2015-01-01

    Ameloblastic fibroma (AF) is an uncommon benign odontogenic tumour, with both epithelial and mesenchymal neoplastic proliferation. It occurs most frequently in the posterior region of the mandible, while its occurrence in the maxilla is extremely rare. They are usually encountered in children, emphasizing it as an important diagnostic consideration. Herein, we report the first case of a bilateral maxillary ameloblastic fibroma in a 2-year-old female child patient who presented with a chief complaint of swelling in the right mid facial region.

  6. Immunohistochemical expression of neural tissue markers (neuron-specific enolase, glial fibrillary acidic protein, S100 protein) in ameloblastic fibrodentinoma: a comparative study with ameloblastic fibroma.

    PubMed

    Takeda, Y; Sato, H; Satoh, M; Nakamura, S I; Yamamoto, H

    2000-08-01

    Formalin-fixed paraffin-embedded sections of three cases of ameloblastic fibrodentinoma (AFD) were studied by the avidin-biotin-peroxidase complex method using antibodies against neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S100 protein and the results were compared with those in ameloblastic fibroma (AF). A striking histopathological characteristic of AFD was the formation of abortive dentin with various degrees of maturation at the epithelial-mesenchymal tissue interface. Central cells of enamel organ-like epithelia with various stages of abortive dentin induction in AFD were generally positive for NSE. Dental lamina-like epithelial cells also showed positive staining in some areas. No cells were positive for NSE in AF. Positive staining for GFAP was observed in the juxta-epithelial mesenchymal tissue of the formation stage of immature dentin with various numbers of entrapped cells in AFD, but GFAP staining was negative in other mesenchymal and epithelial tissues at other stages. In AF, no GFAP-positive cells were found. There were a few S100 protein-positive cells found in the foci of epithelial components in both AFD and AF. Mesenchymal cells showing a dendritic or spindle shape were positive for S100 protein in some areas of AFD and AF. Although such cells in the mesenchymal component of pigmented AFD were more numerous than in non-pigmented AFD and AF, their distribution pattern in the former condition was basically similar to that in the latter. Although the present results, obtained from conventional immunohistochemical procedures, do not directly reflect the expression of neural crest-derived cells in the dentinogenesis of AFD, such results do not disprove the possibility of the expression of neural proteins probably related to neural crest-derived cells in dentinogenesis under certain pathologic conditions in odontogenic mixed tumors. Such a phenomenon may also occur during dentinogenesis in other odontogenic mixed tumors and

  7. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma?

    PubMed

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

    2015-01-01

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

  8. Ameloblastic fibroma and related lesions: a clinicopathologic study with reference to their nature and interrelationship.

    PubMed

    Chen, Yan; Li, Tie-Jun; Gao, Yan; Yu, Shi-Feng

    2005-11-01

    Ameloblastic fibroma (AF) and related lesions constitute a group of lesions, which range in biologic behavior from true neoplasms to hamartomas. The aim of this study was to elucidate the nature and interrelationship of this group of lesions. Clinical and pathological studies were undertaken retrospectively on 13 cases of AF and seven cases of ameloblastic fibro-odontoma (AFO). Thirty-three complex odontomas and 33 compound odontomas were also included for comparative purpose. Relevant follow-up data were recorded and the literature was reviewed. The majority of patients with AF (nine cases, 69.2%) were over the age of 22 years with frequent involvement (76.9%) of the posterior mandible. Tumors recurred in four of 11 patients with follow-up information and two recurrent tumors showed malignant transformation. There was no case in this series that could be designated as the so-called ameloblastic fibrodentinoma, apart from one recurrent AF in which further maturation to form only tubular dentin materials was identified. AFO tended to occur at a younger age group with an average of 9.6 years. Recurrence was noted in two of five patients with follow-up data and both recurrent lesions showed limited growth potential and further maturation into a complex odontoma. Significant differences were noted in the age and site distribution between the complex and the compound odontomas. Whilst the majority, if not all, of AFs are true neoplasms with a potential to recur and/or of malignant transformation, some, especially those occurred during childhood, could represent the primitive stage of a developing odontoma. Our data also suggests that some AFOs are hamartomatous in nature, representing a stage preceding the complex odontoma.

  9. Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat

    PubMed Central

    Li, Yinghua; Bae, Han-Ik; Kim, Hak-Soo; Kang, Min-Soo; Gong, Bo-Ho; Jung, Won-Hee; Lee, Sranna; Bae, Jin-Sook; Kim, Kap-Ho; Song, Si-Whan; Lee, Jae-Hyun; Kang, Boo-Hyon

    2017-01-01

    Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a well demarcated nodule, approximately 2.5 × 2.0 × 2.0 cm, protruded from the ventral area of the right mandible. The nodule was not attached to mandibular bone and was not continuous with the normal teeth. Histopathologically, the tumor was characterized by the simultaneous occurrence of an ameloblastomatous component and composite odontoma-like elements within the same tumor. The epithelial portion formed islands or cords resembling the follicle or plexiform pattern typical of ameloblastoma and was surrounded by mesenchymal tissue. Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel) resembling odontoma was observed in the center of the tumor. Mitotic figures were rare, and areas of cystic degeneration were present. Immunohistochemically, the epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the mesenchymal component and odontoblast-like cells were positive for vimentin, in the same manner as in normal teeth. On the basis of these findings, the tumor was diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular region in a SD rat. In the present study, we report the uncommon spontaneous peripheral ameloblastic odontoma in the SD rat. We also discuss here the morphological characteristics, origin, histochemical, and immunohistochemical features for the diagnosis of this tumor. PMID:28503263

  10. 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. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Chemotherapy responsiveness in a patient with multiply relapsed ameloblastic fibro-odontosarcoma of the maxilla.

    PubMed

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

    2015-11-01

    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.

  12. 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

  13. Stress Response Pathways in Ameloblasts: Implications for Amelogenesis and Dental Fluorosis

    PubMed Central

    Sierant, Megan L.; Bartlett, John D.

    2012-01-01

    Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, an elemental agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed. PMID:23745169

  14. Ameloblastic fibro-odontoma of the anterior mandible in a 22-month-old boy.

    PubMed

    Wewel, John; Narayana, Nagamani

    2010-01-01

    We report an ameloblastic fibro-odontoma (AFO) presenting in the anterior mandible as a "bump on his gums" in a 22-month-old boy. An occlusal radiograph revealed a well-circumscribed radiolucency with scattered radiopaque foci. The tumor was enucleated under general anesthesia. The histologic findings were characteristic of an AFO, a mixed odontogenic tumor most common in the posterior jaws, primarily affecting individuals with an average age of 10 years. The clinical presentation, microscopic findings, differential diagnoses, and treatment are discussed.

  15. Ameloblastic fibroma with ghost cell differentiation and calcification: A unique case report.

    PubMed

    Arora, Manpreet; Dave, Aparna; Shetty, Vishwaprakash; Saluja, Pulin

    2015-01-01

    The ameloblastic fibroma (AF) is an uncommon odontogenic tumor that may present an aggressive behavior and may have potential for malignant transformation. Ghost cell differentiation within AF is extremely rare. There are only seven cases in English literature in which ghost cells are found in AF but all these previously reported cases were associated with typical calcifying odontogenic cyst. Here, we present a unique case in 3(1/2)-year-old child with solid lesion which comprised odontogenic epithelium strands, islands, and myxoid ectomesenchyme with focal areas of ghost cell differentiation and calcification associated with neoplastic epithelium.

  16. Stress response pathways in ameloblasts: implications for amelogenesis and dental fluorosis.

    PubMed

    Sierant, Megan L; Bartlett, John D

    2012-09-01

    Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, an elemental agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed.

  17. Ghost cell odontogenic carcinoma: A rare case report and review of literature

    PubMed Central

    Alberola-Ferranti, Margarita; Hueto-Madrid, Juan Antonio; Bescós-Atín, Coro

    2014-01-01

    Objectives: Ghost cell odontogenic carcinoma is a rare condition characterized by ameloblastic-like islands of epithelial cells with aberrant keratinitation in the form of Ghost cell with varying amounts of dysplastic dentina. Material and Methods: We report a case of a 70 year-old woman with a rapid onset of painful swelling right maxillary tumor. Magnetic resonance showed a huge tumor dependent on the right half of the right hard palate with invasion of the pterygoid process and focally to the second branch of the trigeminal. Radiological stage was T4N0. The patient underwent a right subtotal maxillectomy with clear margins. Adjuvant radiotherapy was given. The patient was free of residual or recurrent disease 12 months after surgery. Results: The tumor was 3,9cm in diameter. It was spongy and whitish gray. Microscopically the tumor was arranged in nets and trabeculae, occasionally forming palisade. Tumoral cells had clear cytoplasm with vesicular nuclei. There was atipia and mitosi with vascular and perineural invasion. The excised tumor was diagnosed as a GCOC. Conclusions: Ghost cell carcinoma is a rare odontogenic carcinoma. Its course is unpredictable, ranging from locally invasive tumors of slow growth to highly aggressive and infiltrative ones. Wide surgical excision with clean margins is the treatment of choice although its combination with postoperative radiation therapy, with or without chemotherapy, remains controversial. Key words:Ameloblastic carcinoma, calcifying odontogenic cyst, Ghost cell carcinoma, keratinizing epithelial odontogenic cyst, maxillary tumor, odontogenic carcinoma. PMID:25674335

  18. [A Long-Surviving Case of Unresectable Gall Bladder Carcinoma Treated with Gemcitabine-Based Chemotherapy].

    PubMed

    Matsukawa, Hiroyoshi; Shiozaki, Shigehiro; Satoh, Daisuke; Araki, Hiroyuki; Mimura, Naoki; Ogawa, Toshihiro; Idani, Hitoshi; Ojima, Yasutomo; Harano, Masao; Kanazawa, Takashi; Choda, Yasuhiro; Sumitani, Daisuke; Ishida, Michihiro; Okajima, Masazumi; Ninomiya, Motoki

    2016-11-01

    We report a 5-year surviving patient with unresectable gall bladder carcinoma treated with gemcitabine(GEM)-based chemotherapy. A 64-year-old man was diagnosed with unresectable gall bladder carcinoma with peritoneal dissemination based on laparotomy findings. Two months later, he started to receive GEM chemotherapy. Twelve months after surgery, the patient chose to suspend GEM treatment. One year and 10 months later, multiple lung metastases appeared and GEM was restarted in combination with UFT. Although the primary lesion and lung metastases gradually progressed, the patient maintained a good quality of life. After 3 years and 2 months, chemotherapy was changed to GEM plus S-1 because of progressive disease. Five years and 2 months after surgery, his condition was complicated by a secondary pneumothorax, and the patient received home oxygen therapy. Five years and 8 months after surgery he died of respiratory distress caused by the progression of lung metastases. Even in the case of unresectable advanced gall bladder carcinoma, effective chemotherapy could improve quality of life and prolong survival.

  19. Quality-of-life evaluation during platinum-based neoadjuvant chemotherapies for urothelial carcinoma.

    PubMed

    Fukushi, Ken; Narita, Takuma; Hatakeyama, Shingo; Yamamoto, Hayato; Soma, Osamu; Matsumoto, Teppei; Tobisawa, Yuki; Yoneyama, Tohru; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Ohyama, Chikara

    2017-04-01

    Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.

  20. A video-based educational pilot for basal cell carcinoma (BCC) treatment: A randomized controlled trial.

    PubMed

    Love, Elyse M; Manalo, Iviensan F; Chen, Suephy C; Chen, Kuang-Ho; Stoff, Benjamin K

    2016-03-01

    Several treatment options exist for uncomplicated basal cell carcinoma. Standardized and effective informed consent is difficult in busy dermatology clinics. We investigated whether an educational video depicting 3 treatment options for uncomplicated basal cell carcinoma-excision, electrodessication and curettage, and topical therapy-before standard in-office informed consent affected patient knowledge and consent time compared with standard in-office consent alone. Patients were randomized to receive video education plus verbal discussion (video) or standard verbal discussion alone (control). Both groups completed baseline and final knowledge assessments. The primary outcome measure was change in knowledge scores between groups. Secondary outcomes were patient satisfaction, physician satisfaction, and informed consent time. In all, 32 eligible patients (16 control, 16 video) from an academic institution and affiliate Department of Veterans Affairs Medical Center dermatology clinics participated. The video group had significantly greater gains in knowledge compared with the control group (mean ± SD: 9 ± 3.6 vs 2.9 ± 2.2) (P = .0048). There was no significant difference in total consent time between groups. Patients and physicians were highly satisfied with the video. Small sample size and slight methodological difference between recruitment sites are limitations. Video-based education for basal cell carcinoma improved patient knowledge with no additional physician time when compared with standard communication. Published by Elsevier Inc.

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

    PubMed

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

    2014-12-01

    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.

  2. 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

  3. Growth of ameloblast-lineage cells in a three-dimensional Matrigel environment.

    PubMed

    Li, Wu; Machule, Darren; Gao, Cen; DenBesten, Pamela K

    2006-05-01

    Enamel organ epithelial cells grow in culture as two distinct cell populations--either stellate-shaped or polygonal-shaped cells. The polygonal cells have an ameloblast cell phenotype and are difficult to grow in culture beyond two passages. This study was designed to determine the effects of a Matrigel three-dimensional (3D) environment on polygonal cells, as compared with stellate cells, derived from porcine tooth enamel organ. Enamel organs were dissected free from the unerupted molars of 30-kg pigs and then grown in LCH-8e media, either with or without serum. Cells grown in serum-free media were primarily polygonal shaped, whereas cells grown in media containing serum were stellate shaped. Both types of cells were grown in a 3D Matrigel matrix. In addition, polygonal-shaped cells were mixed with hydroxyapatite powder and transplanted subcutaneously into nude mice. Polygonal-shaped epithelial cells formed cell groups, similar to epithelial pearls, both in vitro and in vivo. The stellate-shaped cells, in contrast, did not form similar structures, but remained suspended in the Matrigel and gradually disappeared from the culture. These results suggest that a Matrigel environment, rich in basement membrane and matrix proteins, selects for polygonal-shaped ameloblast-lineage cells and induces the formation of epithelial pearls.

  4. Congenital peripheral ameloblastic fibroma with intraosseous involvement in a 2-week-old infant: A case report with review of literature.

    PubMed

    Langer, Sabina; Choudhury, Monisha; Agarwal, Savita; Mehra, Parvesh

    2015-01-01

    Ameloblastic fibroma is a rare, slow-growing benign mixed odontogenic tumor. It constitutes 2% of odontogenic tumors and is reported to occur at an age ranging from 6 months to 42 years. The youngest being a 7-week-old infant. We report a case of peripheral ameloblastic fibroma in a 2-week-old infant. The lesion presented since birth. It involved the maxilla with an extraosseous component involving the gingiva. A more or less conservative surgical approach of enucleation and curettage of the lesion was done under general anesthesia, trying to conserve the adjacent tooth buds. Only a few cases of congenital peripheral ameloblastic fibroma have been reported so far.

  5. 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.

  6. Clear cell carcinoma of the base of the tongue: case report and literature review.

    PubMed

    Watanabe, Kenichi; Okumura, Yuri; Hashimoto, Ken; Suzuki, Takashi

    2015-01-01

    Clear cell carcinoma (CCC) is a rare, low-grade malignant neoplasm of minor salivary glands. Clear cell carcinoma is composed of monomorphic clear cells that contain glycogen within a hyalinized stroma. The microscopic diagnosis can be challenging, and the treatment strategy has not been established. We report a case of a 56-year-old woman with CCC in the base of the tongue. A literature review, including 22 published cases and our case, was performed to clarify the clinical characteristics of CCC in the base of the tongue. The exophytic tumor showed no infiltration to the neighboring tissues. She underwent a local excision en bloc transorally and is free of the disease 15 months after surgery. In our review of 23 cases of CCC in the base of the tongue, 21 cases received surgical excision for the purpose of the primary treatment modality. The fact that the distinctive features of restricted site-related symptoms and the rare presentation of pain emerged was similar to previously reported cases of CCC. A relatively good prognosis was still indicated. We reveal the features of the unusual occurrence of CCC in the base of the tongue and consider the appropriate surgical approach for primary treatment. © The Author(s) 2014.

  7. Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.

    PubMed

    Mateo, Alina M; Pezzi, Todd A; Sundermeyer, Mark; Kelley, Cynthia A; Klimberg, Vicki S; Pezzi, Christopher M

    2016-10-01

    Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB). Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference. Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46). There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Evaluation of somatic genomic imbalances in thyroid carcinomas of follicular origin by CGH-based approaches.

    PubMed

    Baldan, Federica; Mio, Catia; Allegri, Lorenzo; Passon, Nadia; Lepore, Saverio M; Russo, Diego; Damante, Giuseppe

    2017-09-07

    Application of distinct technologies of cancer genome analysis has provided important information for the molecular characterization of several human neoplasia, including follicular cell-derived thyroid carcinoma. Among them, comparative genomic hybridization (CGH)-based procedures have been extensively applied to evaluate genomic imbalances present in these tumours, obtaining data leading to an increase in the understanding of their complexity and diversity. In this review, after a brief overview of the most commonly used CGH-based technichs, we will describe the major results deriving from the most influential studies in the literature which used this approach to investigate the genomic aberrations of thyroid cancer cells. In most studies a small number of patients have been analyzed. Deletions and duplications at different chromosomal regions were detected in all investigated cohorts. A higher number of genomic imbalances has been detected in anaplastic or poorly differentiated thyroid carcinomas compared to well differentiated ones. Limitations in the interpretation of the results, as well the potential impact in the clinical practice are discussed. Though a quite heterogeneous picture arises from results so far available, CGH array, combined with other methodologies as well as an accurate clinical management, may offer novel opportunities for a better stratification of thyroid cancer patients.

  9. Patients with newly diagnosed carcinoma of the breast: validation of a claim-based identification algorithm.

    PubMed

    Leung, K M; Hasan, A G; Rees, K S; Parker, R G; Legorreta, A P

    1999-01-01

    The objectives of this study were to validate a claims-based algorithm for identification of patients with newly diagnosed carcinoma of the breast and to optimize the algorithm. Claims data from all females aged 21 years or older who enrolled in a large California health maintenance organization during the study period from October 1, 1994 through March 31, 1996 were analyzed. Medical records of the patients identified through the claims-based algorithm were reviewed to determine whether the patients were correctly identified. The initial algorithm had a positive predictive value of 84% which was similar to the previous study. The percentages of correct identification significantly increased with the patient's age at diagnosis. Other patient demographic characteristics and facility characteristics were not related to the accuracy of the identification. Using a classification tree procedure and additional information from the false-positive cases, the initial algorithm was modified for improvement. The best-modified algorithm had a positive predictive value of 92% while only 0.5% (4/837) of the true-positive cases were excluded. The results once again demonstrated that patients with newly diagnosed carcinomas of the breast can be identified using claims data. These databases provide an efficient and effective tool for performing health services studies on large patient populations.

  10. Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case control study

    PubMed Central

    Calvocoressi, Lisa; Stowe, Meredith H.; Carter, Darryl; Claus, Elizabeth B.

    2013-01-01

    Background and aim The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case control study in Connecticut, USA. Methods This analysis included 1,179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case-control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals. Results We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR) = 0.85, 95 % confidence interval (CI): 0.65-1.11); of estrogen alone (adjusted OR = 0.93; 95 % CI: 0.68-1.29) or of estrogen and progesterone (adjusted OR = 0.75; 95 % CI: 0.52-1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data. PMID:22317899

  11. A generic RNA pulsed DC based approach for developing therapeutic intervention against nasopharyngeal carcinoma.

    PubMed

    Tyagi, Rajeev K; Parmar, Rajesh; Patel, Naisargee

    2017-04-03

    The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs). The RNA extracted from well-characterized highly immunogenic NPC cells (C666-1) was transfected into MoDCs. The formulated and characterized cationic liposomes were used to achieving efficient RNA transfection of immature DCs. Further, DCs were forcibly matured with a cytokine cocktail to achieve greater expression of MHC and co-stimulatory molecules. Moreover, our results did not see any effect of RNA or lipids on MoDCs phenotype or cytokine expression. RNA loaded DCs derived from HLA-A2-positive donors were shown to activate effector memory cytotoxic T lymphocytes (CTLs) specific for TAAg ligand expressed by C666-1 cells. Our results show the comparison of cytotoxic response mounted against RNA-loaded DCs with those directly stimulated by C666-1 tumor cells. Our findings suggest that DCs expressing tumor cell RNA primed naïve T cells show T cells priming with lesser cytotoxicity and cytokine secretion when exposed with with C666-1 tumor cells. These results surface the potential of DCs to deliver RNA in NPCs, sufficient presentation of RNA to provoke perdurable immune responses against nasopharyngeal carcinoma. Our results implies that DC based vaccine approach may be useful to develop therapeutic interventional approach in the form of vaccine to address NPCs.

  12. 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. Copyright 2004 Wiley-Liss, Inc.

  13. Ameloblastic fibro-odontoma associated with a retained molar in an Oldenburg mare.

    PubMed

    Knowles, Susan; Blas-Machado, Uriel; Butler, Abigail M; Gomez-Ibañez, Sara E; Lowder, Michael Q; Fayrer-Hosken, Richard A

    2010-11-01

    An 11-year-old Oldenburg mare presented with a 3-month history of weight loss and swelling of the posterior right mandible. Physical examination and radiographs showed a soft-tissue mass in the right mandible with foci of mineralization, periosteal proliferation, and a retained molar. The tumor increased in size over several weeks, and the mare was euthanized. On necropsy, a 24 cm × 15 cm × 15 cm firm, white mass had obliterated the posterior right mandible. The mass was multinodular with discrete clusters of blood-filled cystic spaces. Histologically, the mass was composed of neoplastic odontogenic epithelium and pulpal mesenchyme with an accumulation of eosinophilic material resembling dentin or enamel. Microscopic and immunohistochemical staining features of the neoplasm were most consistent with an ameloblastic fibro-odontoma.

  14. Ameloblastic fibroma of the mandible associated with root resorption and unerupted teeth: a case report.

    PubMed

    Dimitrakopoulos, Ioannis; Psomaderis, Konstantinos; Zaramboukas, Thomas

    2008-06-01

    Ameloblastic fibroma (AF) is an uncommon benign odontogenic mixed tumor. A case of an AF associated with unerupted and missing teeth is presented. A 13-year-old girl was referred for evaluation of a painless swelling of her right mandible. The most remarkable finding was the resorption of the proximal root of the permanent first molar. The lesion was completely enucleated. Follow-up showed satisfactory bony healing, and the resorbed root was completely surrounded by a continuous layer of intact lamina dura. In most cases, the patient presents to the clinician complaining of an unerupted tooth at the posterior area of the mandible. The most remarkable finding in our case, however, was the coexisting root resorption. This finding could indicate a more aggressive form of AF. AF has a very good prognosis. Malignant transformation is extremely rare.

  15. Argyrophilic nucleolar organizer regions (AgNORs) in odontogenic myxoma (OM) and ameloblastic fibroma (AF).

    PubMed

    Martins, C; Carvalho, Y R; do Carmo, M A

    2001-09-01

    Ten cases of odontogenic myxoma (OM) and six cases of ameloblastic fibroma (AF) were subjected to comparative analysis by the AgNOR technique, in order to determine a possible difference in cell proliferation index between these lesions. The mean AgNOR number of the mesenchymal component of AF was compared with its epithelial component and the difference was not found to be statistically significant. The mean AgNOR index of the AF group was significantly higher than that of the OM group. Moreover, the mesenchymal component of AF demonstrated increased AgNOR numbers compared with that of OM (P<0.05). These results suggest that the epithelial and mesenchymal components of AF may have similar cell proliferative activity. However, the cell proliferative index of this lesion seems to be higher than that of OM.

  16. Nonfunctioning parathyroid carcinoma

    SciTech Connect

    Klink, B.K.; Karulf, R.E.; Maimon, W.N.; Peoples, J.B. )

    1991-07-01

    Parathyroid carcinoma is a rare clinical entity accounting for only 4 per cent of all cases of parathyroid neoplasia. Nonfunctioning parathyroid carcinoma is even rarer. Previously, virtually all patients with these lesions were treated for a nonspecific neck mass. However, in the present case, a preoperative diagnosis of nonfunctioning parathyroid carcinoma was made based on the technetium pertechnetate/thallium 201 subtraction scan. The authors report on the 14th case of nonfunctioning parathyroid carcinoma, a review of the literature, and guidelines for the preoperative and operative evaluation of neck masses suspected to be parathyroid carcinoma.22 references.

  17. Computer-Assisted Hepatocellular Carcinoma Ablation Planning Based on 3-D Ultrasound Imaging.

    PubMed

    Li, Kai; Su, Zhongzhen; Xu, Erjiao; Guan, Peishan; Li, Liu-Jun; Zheng, Rongqin

    2016-08-01

    To evaluate computer-assisted hepatocellular carcinoma (HCC) ablation planning based on 3-D ultrasound, 3-D ultrasound images of 60 HCC lesions from 58 patients were obtained and transferred to a research toolkit. Compared with virtual manual ablation planning (MAP), virtual computer-assisted ablation planning (CAP) consumed less time and needle insertion numbers and exhibited a higher rate of complete tumor coverage and lower rate of critical structure injury. In MAP, junior operators used less time, but had more critical structure injury than senior operators. For large lesions, CAP performed better than MAP. For lesions near critical structures, CAP resulted in better outcomes than MAP. Compared with MAP, CAP based on 3-D ultrasound imaging was more effective and achieved a higher rate of complete tumor coverage and a lower rate of critical structure injury; it is especially useful for junior operators and with large lesions, and lesions near critical structures.

  18. 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

    2006-11-07

    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.

  19. [Endoscopic surgery and reconstruction for extensive osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma].

    PubMed

    Chen, Z; Qiu, Q H; Zhan, J B; Zhu, Z C; Peng, Y; Liu, H

    2016-12-07

    Objective: To investigate the clinical efficacy of endoscopic surgery for extensive osteoradionecrosis (ORN) of skull base in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: Seventeen patients diagnosed as ORN of skull base after radiotherapy for NPC and underwent endoscopic surgery were retrospectively studied with their clinic data. Results: Based on the CT and endoscopic examination, all patients had large skull base defects with bone defects averaged 7.02 cm(2) (range, 3.60 - 14.19 cm(2)). Excepting for curetting the sequestra, endoscopic surgery was also used to repair the wound or to protect the internal carotid artery with flap in 12 patients. No bone reconstructions were conducted in all patients with the bone defects of skull base. CT examinations were taken after endoscopic surgery when required. The postoperative follow-up ranged from 8 months to 6 years (average, 14 months). Aside from 1 patient with delayed cerebrospinal fluid (CSF), others had no related complications. Conclusions: The patients with extensive ORN can be treated with endoscopic surgery to curette the necrotic bone of skull base, and endoscopic reconstruction provides an alternative technique. It may not be necessary to reconstruct the bone defects at skull base, however, the exposed important structures of skull base, such as internal carotid artery, need to repair with soft tissue such as flap.

  20. Cutaneous horns: clues to invasive squamous cell carcinoma being present in the horn base.

    PubMed

    Pyne, John; Sapkota, Devendra; Wong, Jian Cheng

    2013-04-01

    Cutaneous horns usually develop on a keratinocytic base with the histopathology on a spectrum ranging from benign keratosis through to invasive squamous cell carcinoma (SCC). Some features of horns are easily identified using dermatoscopy. To investigate if specific clinical or dermatoscopy features of horns correlate with the histopathology in the base of the horn. Consecutive horn cases (n=163) were assessed prospectively in vivo for horn height, terrace morphology and base erythema using a Heine Delta 20 dermatoscope. Cases with potentially confounding influences were excluded. A history of horn pain or pain on palpation was also recorded. Benign keratosis (n = 49), actinic keratosis (n = 21), SCC in situ (n = 37) and invasive SCC (n = 56) were recorded. An invasive SCC presenting as a horn as most likely to have a height less than the base diameter, 66% (37/56). Compared to the other study entities, invasive SCC tends to have less terrace morphology (P<0.05), a higher incidence of base erythema (P<0.05) and more pain (P<0.01). Data categories did not include anatomic site or horn growth rates. Excision selection bias favored the incidence of invasive SCC. Horns presenting on an invasive SCC base are more likely to have a height less than the diameter of the base, not to have terrace morphology, to have an erythematous base and to be painful.

  1. Report of Two Cases of Combined Odontogenic Tumors: Ameloblastoma with Odontogenic Keratocyst and Ameloblastic Fibroma with Calcifying Odontogenic Cyst.

    PubMed

    Neuman, Ashley Nicole; Montague, Lindsay; Cohen, Donald; Islam, Nadim; Bhattacharyya, Indraneel

    2015-09-01

    Combined odontogenic neoplasms have rarely been documented. Such tumors have also been described by other researchers as "hybrid" lesions. The histologic features are often identical to other individually well-established odontogenic neoplasms such as ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma (AF), and ameloblastic fibro-odontoma. Their clinical presentation is variable, ranging from cysts to neoplasms showing varying degrees of aggressive behavior. Most combined tumors contain features of one of the odontogenic tumors in combination with either a calcifying odontogenic cyst (COC) or a calcifying epithelial odontogenic tumor. We present two new cases of combined odontogenic tumors: an ameloblastoma with an odontogenic keratocyst and an AF with COC. Predicting clinical outcome is challenging when a combination tumor is encountered due to the paucity of such lesions. One must understand salient features of these entities and differentiate them from the more common conventional neoplasms to expand classification and provide prognostic criteria.

  2. Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

    PubMed

    Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

    2016-04-01

    We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

  3. Ovarian carcinoma: care and survival in a community-based population.

    PubMed

    Yawn, B P; Wollan, P; Klee, M; Barrette, B

    2001-01-01

    Previous studies of the management and costs of ovarian cancer have been based on data from oncology practices. Such studies may exclude patients who are not candidates for treatment and may not account for costs incurred during diagnosis or primary treatment. The purpose of this study was to describe the epidemiology, management, and costs of care of ovarian cancer in a geographically defined population to better reflect the total spectrum of the disease and its care. We conducted a retrospective review of the medical records of all residents of Olmsted County, Minnesota, who received a first diagnosis of epithelial ovarian carcinoma (including postmortem diagnoses) between 1985 and 1997. Of the 107 women with a new diagnosis of ovarian cacinoma, 42 (39%) had stage I or II tumors at the time of diagnosis. The mean age of the patients at the time of diagnosis was 64.7 years, and 20% were nulliparous. The diagnostic assessment for ovarian carcinoma was initiated by a family physician or internist in 50% of cases and by an obstetrician or gynecologist in 16% of cases. One hundred two patients (95%) underwent surgical treatment, and 80 (75%) received primary chemotherapy. The 5-year survival rate was 88% in those with stage I or II tumors and 17% in those with stage III or IV tumors. The mean charges for secondary care were higher than those for primary care ($36,110 vs $32,367; P < 0.05) in those receiving both types of therapy. Fifty percent of those dying of ovarian cancer received hospice care for a mean of 39.0 days before death. Most assessments leading to a diagnosis of ovarian carcinoma were initiated by primary care physicians. In this community-based population, early-stage and low-grade tumors were common (> or = 30%) and were associated with lower costs of care and higher 5-year survival rates. Total treatment costs for those requiring secondary therapy were approximately twice the costs for those requiring primary treatment only, with approximately 50% of

  4. 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.

  5. Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma.

    PubMed

    Pontes, Hélder Antônio Rebelo; Pontes, Flávia Sirotheau Corrêa; Silva, Brunno Santos de Freitas; Cury, Sérgio Elias Vieira; Fonseca, Felipe Paiva; Salim, Rodrigo Alves; Pinto Júnior, Décio dos Santos

    2010-12-01

    Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. 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

  7. [Beta -transduction repeat containing protein expressed in tooth germs and ameloblast and odontoblast of different stage of tooth development].

    PubMed

    Shen, Yong-Dai; Tian, Wei-Dong; Liu, Lei; He, Yong-Houg; Tang, Wei; Zheng, Xiaohui

    2007-04-01

    The Sonic hedgehog signalling peptide has been demonstrated to play important roles in the growth and patterning of the tooth development. This study aims on whether the antagonist beta-transduction repeat containing protein of Sonic hedgehog signal transduction expressed in tooth germs ameloblast and odontoblast or not. The mouse embryo heads of different developmental stages of E10.5, E13.5, E14.5, E16.5, E18.5 and P0, P3, P6 after birth were acquired fixed with 4% paraformaldehyde for 48 hours, embeded with Paraffin and examined using LsAB (labelled streptavidin-biotin) method to observe the beta-TrCP expression pattern in tooth germs, ameloblast and odontoblast. It was demonstrated that beta-TrCP expressed in oral epithelium, tooth bud, mesenchymal cell cytoplasm of ameloblast and odontoblast of different stage of tooth development. beta-TrCP expressed from early stage to later stage of murine tooth development. And these findings provide the evidence of antagonist regulatory pathways for shh in teeth development.

  8. 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

  9. Skull Base Involvement by Acinic Cell Carcinoma of the Parotid Gland

    PubMed Central

    Breen, Joseph T.; Carlson, Matthew L.; Link, Michael J.; Moore, Eric J.; Neff, Brian A.; Driscoll, Colin L.W.

    2012-01-01

    Objective Describe the clinical course and outcomes of patients with primary acinic cell carcinoma (ACC) of the parotid gland with skull base invasion or metastasis. Design Retrospective case series (1995–2011) at a single institution. Results Ten patients met study criteria. Mean and median time from initial diagnosis of parotid ACC to development of skull base disease were 14.6 and 10.2 years, respectively. Two patients demonstrated skull base disease on initial presentation. Those who pursued further treatment after developing disease at the skull base underwent surgery (4/7), stereotactic radiosurgery (4/7), or external beam radiation (3/7). The 10-year Kaplan-Meier estimated overall survival after initial diagnosis of parotid ACC was 80%. Once skull base invasion occurred, 2-year estimated overall survival was 50%. Conclusion Although primary ACC of the parotid generally caries an excellent prognosis, tumor control with cranial base disease is difficult and the majority of patients present with late aggressive recurrences. Our observations underscore the importance of long-term follow-up in this patient group. PMID:24294553

  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. A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma

    PubMed Central

    Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang

    2015-01-01

    Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236

  12. A population-based analysis of verrucous carcinoma of the oral cavity.

    PubMed

    Alonso, Jose E; Kuan, Edward C; Arshi, Armin; St John, Maie A

    2017-08-29

    To describe the incidence and determinants of survival of patients with verrucous carcinoma (VC) of the oral cavity between the years of 1973 and 2012 using the Surveillance, Epidemiology, and End Results (SEER) database. Retrospective cohort study using a national database. The SEER registry was utilized to calculate survival trends for patients with VC of the oral cavity between 1973 and 2012. Patient data was then analyzed with respect to histopathology, age, sex, race, stage, grade, and treatment modalities (surgery and radiation therapy). Overall survival (OS) and disease-specific survival (DSS) were calculated. A total of 1,481 cases of VC of the oral cavity were identified. The cohort was composed of 50.5% males. The mean age at diagnosis was 69.5 years. The oral tongue was the most common primary site (28.9%), followed by the alveolar ridge (21.4%) and buccal mucosa (19.0%). The vast majority of cases (79.1%) presented with stage I and stage II disease. Nodal disease was present in only 1.6% of cases. The median OS was 94.6 months. Eighty-seven percent of cases underwent surgery, and 11.5% received both surgery and radiation therapy. Overall survival at 2, 5, and 10 years was 83%, 64%, and 42%, respectively. On multivariate analysis, advanced age (P < 0.001) and stage (P < 0.001) were associated with worse OS, whereas surgery improved OS (P = 0.047). We provide the first population-based analysis of prognostic factors affecting survival outcomes in patients with oral cavity VC. Verrucous carcinoma of the oral cavity is associated with a generally favorable prognosis. Age, stage, nodal status, and surgical therapy are independent predictors of OS. 4. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Image classification of human carcinoma cells using complex wavelet-based covariance descriptors.

    PubMed

    Keskin, Furkan; Suhre, Alexander; Kose, Kivanc; Ersahin, Tulin; Cetin, A Enis; Cetin-Atalay, Rengul

    2013-01-01

    Cancer cell lines are widely used for research purposes in laboratories all over the world. Computer-assisted classification of cancer cells can alleviate the burden of manual labeling and help cancer research. In this paper, we present a novel computerized method for cancer cell line image classification. The aim is to automatically classify 14 different classes of cell lines including 7 classes of breast and 7 classes of liver cancer cells. Microscopic images containing irregular carcinoma cell patterns are represented by subwindows which correspond to foreground pixels. For each subwindow, a covariance descriptor utilizing the dual-tree complex wavelet transform (DT-[Formula: see text]WT) coefficients and several morphological attributes are computed. Directionally selective DT-[Formula: see text]WT feature parameters are preferred primarily because of their ability to characterize edges at multiple orientations which is the characteristic feature of carcinoma cell line images. A Support Vector Machine (SVM) classifier with radial basis function (RBF) kernel is employed for final classification. Over a dataset of 840 images, we achieve an accuracy above 98%, which outperforms the classical covariance-based methods. The proposed system can be used as a reliable decision maker for laboratory studies. Our tool provides an automated, time- and cost-efficient analysis of cancer cell morphology to classify different cancer cell lines using image-processing techniques, which can be used as an alternative to the costly short tandem repeat (STR) analysis. The data set used in this manuscript is available as supplementary material through http://signal.ee.bilkent.edu.tr/cancerCellLineClassificationSampleImages.html.

  14. 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.

  15. NMFBFS: A NMF-Based Feature Selection Method in Identifying Pivotal Clinical Symptoms of Hepatocellular Carcinoma

    PubMed Central

    Meng, Guanmin; Huang, Deshuang; Yue, Xiaoqiang; Wang, Bing

    2015-01-01

    Background. Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Traditional Chinese Medicine (TCM), with the characteristics of syndrome differentiation, plays an important role in the comprehensive treatment of HCC. This study aims to develop a nonnegative matrix factorization- (NMF-) based feature selection approach (NMFBFS) to identify potential clinical symptoms for HCC patient stratification. Methods. The NMFBFS approach consisted of three major steps. Firstly, statistics-based preliminary feature screening was designed to detect and remove irrelevant symptoms. Secondly, NMF was employed to infer redundant symptoms. Based on NMF-derived basis matrix, we defined a novel similarity measurement of intersymptoms. Finally, we converted each group of redundant symptoms to a new single feature so that the dimension was further reduced. Results. Based on a clinical dataset consisting of 407 patient samples of HCC with 57 symptoms, NMFBFS approach detected 8 irrelevant symptoms and then identified 16 redundant symptoms within 6 groups. Finally, an optimal feature subset with 39 clinical features was generated after compressing the redundant symptoms by groups. The validation of classification performance shows that these 39 features obviously improve the prediction accuracy of HCC patients. Conclusions. Compared with other methods, NMFBFS has obvious advantages in identifying important clinical features of HCC. PMID:26579207

  16. Differentiation of mouse iPS cells into ameloblast-like cells in cultures using medium conditioned by epithelial cell rests of Malassez and gelatin-coated dishes.

    PubMed

    Yoshida, Koki; Sato, Jun; Takai, Rie; Uehara, Osamu; Kurashige, Yoshihito; Nishimura, Michiko; Chiba, Itsuo; Saitoh, Masato; Abiko, Yoshihiro

    2015-09-01

    Induced pluripotent stem (iPS) cells are generated from adult cells and are potentially of great value in regenerative medicine. Recently, it was shown that iPS cells can differentiate into ameloblast-like cells in cultures using feeder cells. In the present study, we sought to induce differentiation of ameloblast-like cells from iPS cells under feeder-free conditions using medium conditioned by cultured epithelial cell rests of Malassez (ERM) cells and gelatin-coated dishes. Two culture conditions were compared: co-cultures of iPS cells and ERM cells; and, culture of iPS cells in ERM cell-conditioned medium. Differentiation of ameloblast-like cells in the cultures was assessed using real-time RT-PCR assays of expression of the marker genes keratin 14, amelogenin, and ameloblastin and by immunocytochemical staining for amelogenin. We found greater evidence of ameloblast-like cell differentiation in the cultures using the conditioned medium. In the latter, the level of amelogenin expression increased daily and was significantly higher than controls on the 7th, 10th, and 14th days. Expression of ameloblastin also increased daily and was significantly higher than controls on the 14th day. The present study demonstrates that mouse iPS cells can be induced to differentiate into ameloblast-like cells in feeder-free cell cultures using ERM cell-conditioned medium and gelatin-coated dishes.

  17. Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma.

    PubMed

    Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

    2015-02-28

    To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P<0.001) and objective tumor response (P=0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P=0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P<0.001). Multivariate analysis identified tumor stage (P<0.001) and tumor type (P=0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P<0.001), surgical treatment (P=0.009), and multi-modal treatment (P=0.002) were identified as independent post-treatment prognostic factors. TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC.

  18. Identifying potential clinical syndromes of hepatocellular carcinoma using PSO-based hierarchical feature selection algorithm.

    PubMed

    Ji, Zhiwei; Wang, Bing

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Clinical symptoms attributable to HCC are usually absent, thus often miss the best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an active role in diagnosis and treatment of HCC. In this paper, we proposed a particle swarm optimization-based hierarchical feature selection (PSOHFS) model to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical feature representation is developed by a three-layer tree. The clinical symptoms and positive score of patient are leaf nodes and root in the tree, respectively, while each syndrome feature on the middle layer is extracted from a group of symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced feature space to search an optimal syndrome subset. Based on the result of feature selection, the causal relationships of symptoms and syndromes are inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated into 27 groups and 27 syndrome features were extracted. The proposed approach discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally, the Bayesian approach was applied to represent the causal relationships both at symptom and syndrome levels. The results show that our computational model can facilitate the clinical diagnosis of HCC.

  19. 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

  20. 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

  1. Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis.

    PubMed

    Schaapveld, Michael; Jorna, Francisca H; Aben, Katja K H; Haak, Harm R; Plukker, John T M; Links, Thera P

    2011-11-01

    Parathyroid carcinoma is a rare malignancy and generally is diagnosed after surgery for primary hyperparathyroidism. Lack of a preoperative diagnosis and ill-considered surgical planning with its impact on survival are ill-described. In a retrospective population-based cohort study the clinical features, treatment, recurrences, and survival of 41 parathyroid cancer patients are reported and compared with characteristics of patients with primary hyperparathyroidism. Patients with parathyroid carcinoma had significantly higher serum parathyroid hormone and calcium levels compared with patients with primary hyperparathyroidism. Nineteen patients (46%) had a palpable neck mass. A parathyroid hormone level more than 3 times the upper normal limits was suspicious and levels more than 10 times carried a positive predictive value of 84% for carcinoma. Ten-year recurrence-free and disease-specific survival rates were 71% and 79%, respectively. Parathyroid hormone levels of more than 3 times upper normal limits, palpable neck mass, and profound hypercalcemia are suspicious signs of carcinoma necessitating surgical exploration by an experienced surgeon. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. 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

  3. 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

  4. 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. © 2015 American Society for Bone and Mineral Research.

  5. Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor

    PubMed Central

    Seidel, Kerstin; Ahn, Christina P.; Lyons, David; Nee, Alexander; Ting, Kevin; Brownell, Isaac; Cao, Tim; Carano, Richard A. D.; Curran, Tom; Schober, Markus; Fuchs, Elaine; Joyner, Alexandra; Martin, Gail R.; de Sauvage, Frederic J.; Klein, Ophir D.

    2010-01-01

    In many organ systems such as the skin, gastrointestinal tract and hematopoietic system, homeostasis is dependent on the continuous generation of differentiated progeny from stem cells. The rodent incisor, unlike human teeth, grows throughout the life of the animal and provides a prime example of an organ that rapidly deteriorates if newly differentiated cells cease to form from adult stem cells. Hedgehog (Hh) signaling has been proposed to regulate self-renewal, survival, proliferation and/or differentiation of stem cells in several systems, but to date there is little evidence supporting a role for Hh signaling in adult stem cells. We used in vivo genetic lineage tracing to identify Hh-responsive stem cells in the mouse incisor and we show that sonic hedgehog (SHH), which is produced by the differentiating progeny of the stem cells, signals to several regions of the incisor. Using a hedgehog pathway inhibitor (HPI), we demonstrate that Hh signaling is not required for stem cell survival but is essential for the generation of ameloblasts, one of the major differentiated cell types in the tooth, from the stem cells. These results therefore reveal the existence of a positive-feedback loop in which differentiating progeny produce the signal that in turn allows them to be generated from stem cells. PMID:20978073

  6. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma.

    PubMed

    Machens, Andreas; Dralle, Henning

    2007-05-01

    Since DNA tests have enabled reliable identification of asymptomatic RET (rearranged during transfection) gene carriers, myriads of publications have appeared on genotype-phenotype relationships. A comprehensive appraisal of this body of evidence using evidence-based methodology is pending. This study was based on systematic evaluation of the literature using evidence-based criteria. (1) There is a distinct age-related progression of hereditary medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2) Among the high-risk RET mutations, those in codon 634 cause higher penetrance rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma, and parathyroid hyperplasia/adenoma) than mutations in codons 609, 611, 618, and 620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA-based screening is superior to calcitonin-based screening in asymptomatic RET carriers (grade C). (4) Using a worst-case scenario, i.e., considering the earliest finding of MTC in asymptomatic RET carriers, pre-emptive thyroidectomy should be performed before that time (grade C) to be truly prophylactic. Specifically, for carriers of highest-risk mutations (codon 918): within the first year of life; for carriers of high-risk mutations (codon 609, 611, 618, 620, 630, and 634): before the age of 5 years; and for carriers of least-high risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5-10 years. Strict adherence to these grade C recommendations can result in undertreatment of the former (codon 634) and overtreatment of the latter. These genotype-phenotype correlations provide a solid foundation on which to base surgical concepts, leaving little room for randomized controlled clinical trials.

  7. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.

    PubMed

    Malandrino, Pasqualino; Al Ghuzlan, Abir; Castaing, Marine; Young, Jacques; Caillou, Bernard; Travagli, Jean-Paul; Elias, Dominique; de Baere, Thierry; Dromain, Clarisse; Paci, Angelo; Chanson, Philippe; Schlumberger, Martin; Leboulleux, Sophie; Baudin, Eric

    2010-09-01

    To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.

  8. Current State of Gastric Stump Carcinoma in Japan: Based on the Results of a Nationwide Survey

    PubMed Central

    Nomura, Eiji; Lee, Sang-Woong; Kaminishi, Michio; Sugiyama, Mitsugu; Aikou, Takashi; Kitajima, Masaki

    2010-01-01

    Background Carcinoma of the gastric remnant after partial gastrectomy for benign disease or cancer is unusual but an important cancer model. The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy (JSSPMG) performed a nationwide questionnaire survey to understand the current state of gastric stump carcinoma in Japan. Methods In the questionnaire survey of November 2008, gastric stump carcinoma was defined as an adenocarcinoma of the stomach occurring 10 years or more after Billroth I or Billroth II gastrectomy for benign condition or cancer disease. The survey was conducted at the request of reports on five or more patients with gastric stump carcinoma for each institution. Items for the survey included gender, age, methods of reconstruction in an original gastrectomy, original diseases, time interval between original gastrectomy and first detection of stump carcinomas, locations of stump carcinomas, tumor histology, tumor depth, and extent of lymph node metastasis. The questionnaire was sent to 163 surgical institutions in the JSSPMG. Results Ninety-five institutions (58.3%) responded to the survey, and the data of 887 patients satisfied the required conditions for the survey. A total of 887 patients were composed of 368 patients who received Billroth I distal gastrectomy and 519 who received Billroth II. The Billroth II group has a significantly higher number of original benign lesions than the Billroth I group (P < 0.001). This study confirmed the following issues: (1) The remnant stomach after gastrectomy for cancer disease had a higher prevalence to develop stump carcinomas occurring in a shorter time interval since original gastrectomy; (2) Patients with Billroth II gastrectomy had stump carcinomas most frequently in the anastomotic area, but not in the non-stump area as in Billroth I gastrectomy; (3) Tumor histology of 72.4% of 304 stump carcinomas at an early stage was intestinal type adenocarcinoma, i.e., well or moderately

  9. Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 2000 to 2010.

    PubMed

    Muzic, John G; Schmitt, Adam R; Wright, Adam C; Alniemi, Dema T; Zubair, Adeel S; Olazagasti Lourido, Jeannette M; Sosa Seda, Ivette M; Weaver, Amy L; Baum, Christian L

    2017-06-01

    To determine population-based incidence estimates of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). We reviewed the medical records of a population-based cohort diagnosed with nonmelanoma skin cancer between January 2, 2000, and December 31, 2010. The age- and sex-adjusted incidence rates were calculated and compared with estimates from previous periods. The age-adjusted BCC incidence (cases per 100,000 person-years) was 360.0 (95% CI, 342.5-377.4) in men and 292.9 (95% CI, 278.6-307.1) in women. The age-adjusted cSCC incidence (cases per 100,000 person-years) was 207.5 (95% CI, 193.9-221.1) in men and 128.8 (95% CI, 119.4-138.2) in women. From years 1976 to 1984 to years 2000 to 2010, the age- and sex-adjusted incidence (cases per 100,000 person-years) of BCC increased from 222.0 (95% CI, 204.5-239.5) to 321.2 (95% CI, 310.3-332.2) and that of cSCC from 61.8 (95% CI, 52.3-71.4) to 162.5 (95% CI, 154.6-170.3). Over time, the anatomical distribution of BCC shifted from the head and neck to the torso and that of cSCC shifted from the head and neck to the extremities. The incidences of BCC and cSCC are increasing, with a disproportionate increase in cSCC relative to BCC. There is also a disproportionate increase in the incidence of both tumors in women, as well as a shift of anatomical distributions. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Non-computer-assisted liquid-based cytology for diagnosis of oral squamous cell carcinoma.

    PubMed

    Pérez-Sayáns, M; Reboiras-López, M D; Gayoso-Diz, P; Seijas-Naya, F; Antúnez-López, J R; Gándara-Rey, J M; García-García, A

    2012-01-01

    The development of oral squamous cell carcinoma (OSCC) occasionally follows the neoplastic progression of other premalignant lesions. Although biopsy is the definitive diagnostic method, liquid-based cytology is an adequate method for screening suspicious lesions. We compared liquid-based cytology to histology for diagnosis of OSCC in patients with oral lesions that raised clinical suspicion of malignancy. Our sample consisted of 48 patients. Cytological samples were obtained by scraping the lesion superficially using Cytobrush®. We conducted cytological and histopathological evaluation of all preparations. We estimated sensitivity and specificity levels as well as positive and negative predictive values. The degree of inter-observer agreement for both methods was assessed using the kappa index. Twenty-eight (58.3%) of the cases finally were diagnosed with OSCC and 20 (41.7%) were determined to be premalignant lesions. We observed eight false negatives and no false positives; OSCC prevalence was 56.5%. The values for diagnostic indices were: sensitivity, 69% (CI 95%, prevalence 51.87); specificity, 100%; positive predictive value, 100%; negative predictive value, 71% (CI 95% 54.82). A kappa index of 0.622 (CI 95% 0.93, 0.39) was observed.

  12. Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma

    PubMed Central

    Miller, Natalie J.; Bhatia, Shailender; Parvathaneni, Upendra; Iyer, Jayasri G.; Nghiem, Paul

    2013-01-01

    Opinion statement Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a disease-specific mortality of approximately 40 %. The association of MCC with a recently discovered polyomavirus, combined with the increased incidence and mortality of MCC among immunocompromised patients, highlight the importance of the immune system in controlling this cancer. Initial management of MCC is summarized within the NCCN guidelines and in recently published reviews. The high rate of recurrent and metastatic disease progression in MCC, however, presents a major challenge in a cancer that lacks mechanism-based, disease-specific therapies. Traditional treatment approaches have focused on cytotoxic chemotherapy that, despite frequent initial efficacy, rarely provides durable responses and has high morbidity among the elderly. In addition, the immunosuppressive nature of chemotherapy is of concern when treating a virus-associated cancer for which survival is unusually tightly linked to immune function. With a median survival of 9.6 months after development of an initial metastasis (n=179, described herein), and no FDA-approved agents for this cancer, there is an urgent need for more effective treatments. We review diverse management options for patients with advanced MCC, with a focus on emerging and mechanism-based therapies, some of which specifically target persistently expressed viral antigens. These treatments include single-dose radiation and novel immunotherapies, some of which are in clinical trials. Due to their encouraging efficacy, low toxicity, and lack of immune suppression, these therapies may offer viable alternatives to traditional cytotoxic chemotherapy. PMID:23436166

  13. 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.

  14. FT-IR microspectroscopic imaging of human carcinoma thin sections based on pattern recognition techniques.

    PubMed

    Lasch, P; Naumann, D

    1998-02-01

    FT-IR microspectroscopic maps of unstained thin sections from human melanoma and colon carcinoma tissues were obtained on a conventional infrared microscope equipped with an automatic x, y stage. Mapped infrared data were analyzed by different image re-assembling techniques, namely functional group mapping ("chemical mapping") and, for the first time by cluster analysis, principal component analysis and artificial neural networks. The output values of the different classifiers were recombined with the original spatial information to construct IR-images whose color or gray tones were based on the spatial distribution of individual spectral patterns. While the functional group mapping technique could not reliably differentiate between the different tissue regions, the approach based on pattern recognition yielded images with a high contrast that confirmed standard histopathological techniques. The new technique turned out to be particularly helpful to improve discrimination between different types of tissue structures in general, and to increase image contrast between normal and cancerous regions of a given tissue sample.

  15. Proteomics-based identification of plasma biomarkers in oral squamous cell carcinoma.

    PubMed

    Tung, Chun-Liang; Lin, Szu-Ting; Chou, Hsiu-Chuan; Chen, Yi-Wen; Lin, Hwan-Chung; Tung, Chung-Liang; Huang, Kao-Jean; Chen, Yi-Ju; Lee, Ying-Ray; Chan, Hong-Lin

    2013-03-05

    Oral squamous cell carcinoma (OSCC) is an aggressive cancer and its occurrence is closely related to betel nut chewing in Taiwan. However, there are few prognostic and diagnostic biomarkers for this disease especially for its association with betel nut chewing. Recent progresses in quantitative proteomics have offered opportunities to discover plasma proteins as biomarkers for tracking the progression and for understanding the molecular mechanisms of OSCC. In present study, plasma samples from OSCC patients with at least 5-year history of betel nut chewing and healthy donors were analyzed by fluorescence 2D-DIGE-based proteomic analysis. Totally, 38 proteins have been firmly identified representing 13 unique gene products. These proteins mainly function in inflammatory responses (such as fibrinogen gamma chain) and transport (Apolipoprotein A-I). Additionally, the current quantitative proteomic approach has identified numerous OSCC biomarkers including fibrinogen (alpha/beta/gamma) chain, haptoglobin, leucine-rich alpha-2-glycoprotein and ribosomal protein S6 kinase alpha-3 (RSK2) which have not been reported and may be associated with the progression and development of the disease. In summary, this study reports a comprehensive patient-based proteomic approach for the identification of potential plasma biomarkers in OSCC. The potential of utilizing these markers for screening and treating OSCC warrants further investigations.

  16. Extended lateral pharyngotomy for selected squamous cell carcinomas of the lateral tongue base.

    PubMed

    Laccourreye, Ollivier; Seccia, Veronica; Ménard, Madeleine; Garcia, Dominique; Vacher, Christian; Holsinger, F Christopher

    2009-06-01

    In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control. The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months). The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively. Such results suggest that extended

  17. Modification of Acid-Base Balance in Cirrhotic Patients Undergoing Liver Resection for Hepatocellular Carcinoma

    PubMed Central

    Cucchetti, Alessandro; Siniscalchi, Antonio; Ercolani, Giorgio; Vivarelli, Marco; Cescon, Matteo; Grazi, Gian Luca; Faenza, Stefano; Pinna, Antonio Daniele

    2007-01-01

    Objective: To examine modifications of acid-base balance of cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Summary Background Data: Acid-base disorders are frequently observed in cirrhotics; however, modifications during hepatectomy and their impact on prognosis have never been investigated. Methods: Two hundred and two hepatectomies for HCC on cirrhosis were reviewed. Arterial blood samples were collected immediately before and at the end of resection. Preresection and postresection acid-base parameters were compared and related to patient characteristics and postoperative course. The accuracy of acid-base parameters in predicting postoperative liver failure, defined as an impairment of liver function after surgery that led to patient death or required transplantation, was assessed using receiver operating characteristic analysis (ROC). Results: All patients showed a significant reduction in pH, bicarbonate, and base excess at the end of hepatectomy (P < 0.001 in all cases), worsened by intraoperative blood loss (P < 0.010) and preoperative Model for end-stage liver disease score ≥11 (P < 0.010). ROC curve analysis identifies patients with postresection bicarbonate <19.4 mmol/L at high risk for liver failure (50.0%) whereas levels >22.1 mmol/L did not lead to the event (0%; P < 0.001). Postoperative prolongation of prothrombin time and increases in bilirubin, creatinine, and morbidity were also more frequent in patients with lower postresection bicarbonate, resulting in a longer in-hospital stay. Conclusion: In cirrhotic patients, a trend toward a relative acidosis can be expected during surgery and is worsened by the severity of the underlying liver disease and intraoperative blood loss. Postresection bicarbonate level lower than 19.4 mmol/L is an adverse prognostic factor. PMID:17522516

  18. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. 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

  20. Application of Recursive Partitioning to Derive and Validate a Claims-Based Algorithm for Identifying Keratinocyte Carcinoma (Nonmelanoma Skin Cancer).

    PubMed

    Chan, An-Wen; Fung, Kinwah; Tran, Jennifer M; Kitchen, Jessica; Austin, Peter C; Weinstock, Martin A; Rochon, Paula A

    2016-10-01

    Keratinocyte carcinoma (nonmelanoma skin cancer) accounts for substantial burden in terms of high incidence and health care costs but is excluded by most cancer registries in North America. Administrative health insurance claims databases offer an opportunity to identify these cancers using diagnosis and procedural codes submitted for reimbursement purposes. To apply recursive partitioning to derive and validate a claims-based algorithm for identifying keratinocyte carcinoma with high sensitivity and specificity. Retrospective study using population-based administrative databases linked to 602 371 pathology episodes from a community laboratory for adults residing in Ontario, Canada, from January 1, 1992, to December 31, 2009. The final analysis was completed in January 2016. We used recursive partitioning (classification trees) to derive an algorithm based on health insurance claims. The performance of the derived algorithm was compared with 5 prespecified algorithms and validated using an independent academic hospital clinic data set of 2082 patients seen in May and June 2011. Sensitivity, specificity, positive predictive value, and negative predictive value using the histopathological diagnosis as the criterion standard. We aimed to achieve maximal specificity, while maintaining greater than 80% sensitivity. Among 602 371 pathology episodes, 131 562 (21.8%) had a diagnosis of keratinocyte carcinoma. Our final derived algorithm outperformed the 5 simple prespecified algorithms and performed well in both community and hospital data sets in terms of sensitivity (82.6% and 84.9%, respectively), specificity (93.0% and 99.0%, respectively), positive predictive value (76.7% and 69.2%, respectively), and negative predictive value (95.0% and 99.6%, respectively). Algorithm performance did not vary substantially during the 18-year period. This algorithm offers a reliable mechanism for ascertaining keratinocyte carcinoma for epidemiological research in the absence of

  1. Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy.

    PubMed

    Han, Bing; Du, Ye; Fu, Ton; Fan, Zhimin; Xu, Shuping; Hu, Chengxu; Bi, Lirong; Gao, Ting; Zhang, Haipeng; Xu, Weiqing

    2017-02-01

    The aim of this study was to find the differences and relationships between normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) lesions of the breast based on biochemical characteristics determined by Raman spectroscopy (RS). After collecting 39 frozen sections from patients who underwent surgical resection or mammotome biopsy, nine normal tissues, seven ADH, eight DCIS, and 15 IDC lesions were detected using confocal RS. We then used leave-one-out cross-validation (LOOCV) and radial basis function (RBF) to build a support vector machine (SVM) diagnosis model. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS, and IDC tissues. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The major spectra differences in ADH, DCIS, and IDC spectrograms were evidenced by a red shift with a broad peak of CH2 (1301 cm(-1)), the intensity of the stretching vibration peak of carotenoids (1526 cm(-1)), a relatively strong band of amide-I (1656 cm(-1)), and the nuclear (882 cm(-1)) acid peak. Atypical ductal hyperplasia tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The overall accuracy of SVM model is 74.39%. The sensitivities of normal tissue, ADH, DCIS, and IDC are 62.5%, 50%, 90%, and 66.7%, respectively. The specificities of normal tissue, ADH, DCIS, and IDC are 100%, 100%, 66.7%, and 89.06%, respectively. Atypical ductal hyperplasia shows significant differences and the relationship between normal tissue and malignant disease. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH converts to DCIS and to IDC.

  2. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    PubMed

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  3. 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

  4. Label-free discrimination of different stage nasopharyngeal carcinoma tissue based on Raman spectroscopy

    PubMed Central

    QIU, SUFANG; HUANG, QINGTING; HUANG, LINGLING; LIN, JINYONG; LU, JUN; LIN, DUO; CAO, GANG; CHEN, CHAO; PAN, JIANJI; CHEN, RONG

    2016-01-01

    The present study aimed to evaluate a label-free tissue test for the detection of nasopharyngeal carcinoma (NPC) at early and advanced stages using Raman spectroscopy (RS). RS measurements were performed to acquire high quality Raman spectra on two groups of tissue samples: One group consists of 30 NPC patients at the early stages (I–II), and the other group is 46 NPC patients at the advanced stages (III–IV). Tentative assignment of Raman bands showed specific biomolecular changes associated with cancer development. Furthermore, effective diagnostic algorithms based on principal components analysis (PCA) and linear discriminant analysis (LDA) were applied for distinguishing Raman spectra of nasopharyngeal tissues from different stages, yielding a diagnostic sensitivity of 70% and a specificity of 78%. This exploratory work suggests that RS in conjunction with the PCA-LDA algorithms provides good diagnostic ability for the early and the advanced staged NPC tissues, and RS has enormous potential for the non-invasive detection of early and advanced stage NPC. PMID:27073522

  5. Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma

    PubMed Central

    Wu, Bingli; Li, Chunquan; Du, Zepeng; Yao, Qianlan; Wu, Jianyi; Feng, Li; Zhang, Pixian; Li, Shang; Xu, Liyan; Li, Enmin

    2014-01-01

    LCN2 (lipocalin 2) is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. LCN2 is elevated in various cancers including esophageal squamous cell carcinoma (ESCC). In this study, LCN2 was overexpressed in the EC109 ESCC cell line and we applied integrated analyses of the gene expression data to identify protein-protein interactions (PPI) network to enhance our understanding of the role of LCN2 in ESCC. Through further mining of PPI sub-networks, hundreds of differentially expressed genes (DEGs) were identified to interact with thousands of other proteins. Subcellular localization analyses found the DEGs and their directly or indirectly interacting proteins distributed in multiple layers, which was applied to analyze the possible paths between two DEGs. Gene Ontology annotation generated a functional annotation map and found hundreds of significant terms, especially those associated with the known and potential roles of LCN2 protein. The algorithm of Random Walk with Restart was applied to prioritize the DEGs and identified several cancer-related DEGs ranked closest to LCN2 protein. These analyses based on PPI network have greatly expanded our understanding of the mRNA expression profile of LCN2 overexpresssion for future examination of the roles and mechanisms of LCN2. PMID:24954627

  6. Comparing histopathological and magnetic resonance imaging based mesorectal fascia status in patients with rectal carcinoma.

    PubMed

    Hassan, Usman; Khan, Rizwanullah; Mehmood, Muhammad Tariq

    2014-04-01

    To compare mesorectal fascia status on histopathological findings with MRI based radiological mesorectal fascia status in patients with rectal carcinoma taking histopathology finding as gold standard. Analytical study. Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from January 2011 to April 2012. Biopsy proven cases of rectal adenocarcinoma undergoing abdominoperineal resection were included in this study. Microscopic examination of slides was done to determine mesorectal fascia status as involved or otherwise without knowing the results of mesorectal fascia status on MRI. Mesorectal fascia status of MRI was determined by a radiologist who was not aware of the histopathological assessment of mesorectal fascia. Mean and standard deviation was calculated for age. Frequency and percentage were calculated for gender and mesorectal fascia status. 2 x 2 table was generated to calculate sensitivity, specificity, positive predictive value and negative predictive values and diagnostic accuracy of MRI for mesorectal fascia involvement taking histopathology as gold standard. The sensitivity of MRI to detect mesorectal fascia involvement was 23.07% and specificity was 70.5%. Positive predictive value of MRI was 10% and negative predictive value was 54.54%. Diagnostic accuracy of MRI for mesorectal fascia involvement was calculated as 50%. MRI findings regarding mesorectal fascia status as involved or otherwise are not helpful when compared with histopathological findings which is the gold standard.

  7. Novel chemoimmunotherapeutic strategy for hepatocellular carcinoma based on a genome-wide association study

    PubMed Central

    Goto, Kaku; Annan, Dorcas A.; Morita, Tomoko; Li, Wenwen; Muroyama, Ryosuke; Matsubara, Yasuo; Ito, Sayaka; Nakagawa, Ryo; Tanoue, Yasushi; Jinushi, Masahisa; Kato, Naoya

    2016-01-01

    Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates. Indeed, the HDACi-induced expression of MICA specific to HCC cells enhanced natural killer (NK) cell-mediated cytotoxicity in co-culture, which was further reinforced by treatment with an inhibitor of MICA sheddase. Similarly augmented anti-tumor activity of NK cells via NK group 2D was observed in vivo. Metabolomics analysis revealed HDACi-mediated alterations in energy supply and stresses for MICA induction and HCC inhibition, providing a mechanism for the chemoimmunotherapeutic actions. These data are indicative of promising strategies for selective HCC innate immunotherapy. PMID:27910927

  8. SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

    PubMed Central

    Luo, Yanzhang; Mok, Tin Seak; Lin, Xiuxian; Zhang, Wanling; Cui, Yizhi; Guo, Jiahui; Chen, Xing; Zhang, Tao; Wang, Tong

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC. PMID:28117408

  9. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

    PubMed

    Rethman, Michael P; Carpenter, William; Cohen, Ezra E W; Epstein, Joel; Evans, Caswell A; Flaitz, Catherine M; Graham, Frank J; Hujoel, Philippe P; Kalmar, John R; Koch, Wayne M; Lambert, Paul M; Lingen, Mark W; Oettmeier, Bert W; Patton, Lauren L; Perkins, David; Reid, Britt C; Sciubba, James J; Tomar, Scott L; Wyatt, Alfred D; Aravamudhan, Krishna; Frantsve-Hawley, Julie; Cleveland, Jennifer L; Meyer, Daniel M

    2012-05-01

    This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

  10. Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy.

    PubMed

    Tsai, Ming-Rung; Shieh, Dar-Bin; Lou, Pei-Jen; Lin, Chih-Feng; Sun, Chi-Kuang

    2012-05-01

    In vivo higher-harmonic generation microscopy (HGM) performed on healthy human oral mucosa not only provides images with a <500 nm lateral resolution at a 280 μm penetration depth, but also leaves no photodamages in the tissues. These advantages suggest that HGM could serve as an ideal virtual biopsy tool for in vivo, in situ, and immediate histopathological diagnosis of oral cancer. However, translation of such mechanism for clinical cancer diagnosis requires evidence based algorithm capable to differentiate cancerous tissues from normal. It is thus critical to investigate if the endogenous contrast provided by the HGM would be high enough to differentiate cancerous versus normal tissues in human oral mucosa. In this report, ex vivo HGM study was performed on the cancerous mucosa from 10 patients with oral squamous cell carcinoma. Compared with histology, HGM revealed histopathological features including the cytological abnormalities, loss of differentiation, interruption of basement membrane, and irregular epithelial stratification in all 10 specimens. In addition, distinct patterns of collagen fibers and increased distribution area of actin filaments in tumor cells were noted. These results indicate HGM holds great potential for the optical biopsy screening of oral cancer lesions.

  11. Planning study for Merkel cell carcinoma based on the relapse pattern.

    PubMed

    Hoeller, Ulrike; Schubert, Tina; Mueller, Thomas; Budach, Volker; Ghadjar, Pirus; Brenner, Winfried; Kuschke, Wolf

    2017-04-01

    To develop a technique for radiation (RT) of in-transit path ways (IT) in Merkel cell carcinoma. In the planning study, IT were ink-marked on the skin during sentinel lymphscintigraphy and wire-marked in planning-CT. Pre- and post-operative planning-CTs were acquired. The clinical target volume (CTV) included tumor bed plus safety margin, IT and draining nodes, the planning volume (PTV) the CTV plus 0.5-1cm margin. VMAT plans with 2-3 arcs were analyzed. A planning study was performed for five pts. including two pts. with primary tumor (PT) in head and neck, 1 pt. each with PT of elbow, forearm and upper leg respectively. Plans showed satisfactory PTV coverage: Dmean 100%±0%, D98% 92.4%±2.24%, homogeneity index (HI) 0.095±0.01, conformation number (CN) 0.84±0.01 and conformality index (CI) 0.95±0.01. The planning study confirms feasibility of highly conformal irradiation of IT pathways based on individualized target delineation. Currently, patients referred for non-metastatic MCC are encouraged to enroll in a prospective clinical study that evaluates the feasibility of radiation of IT pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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.

  13. An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma

    PubMed Central

    Kalinich, Mark; Bhan, Irun; Kwan, Tanya T.; Miyamoto, David T.; Javaid, Sarah; LiCausi, Joseph A.; Milner, John D.; Hong, Xin; Goyal, Lipika; Sil, Srinjoy; Choz, Melissa; Ho, Uyen; Kapur, Ravi; Muzikansky, Alona; Zhang, Huidan; Weitz, David A.; Sequist, Lecia V.; Ryan, David P.; Chung, Raymond T.; Zhu, Andrew X.; Isselbacher, Kurt J.; Ting, David T.; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.

    2017-01-01

    Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens. As proof of principle, we examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, we used a cross-validated logistic regression model to identify the presence of HCC-derived CTCs in nine of 16 (56%) untreated patients with HCC versus one of 31 (3%) patients with nonmalignant liver disease at risk for developing HCC (P < 0.0001). Positive CTC scores declined in treated patients: Nine of 32 (28%) patients receiving therapy and only one of 15 (7%) patients who had undergone curative-intent ablation, surgery, or liver transplantation were positive. RNA-based digital CTC scoring was not correlated with the standard HCC serum protein marker alpha fetoprotein (P = 0.57). Modeling the sequential use of these two orthogonal markers for liver cancer screening in patients with high-risk cirrhosis generates positive and negative predictive values of 80% and 86%, respectively. Thus, digital RNA quantitation constitutes a sensitive and specific CTC readout, enabling high-throughput clinical applications, such as noninvasive screening for HCC in populations where viral hepatitis and cirrhosis are prevalent. PMID:28096363

  14. Elective Neck Dissection for Head and Neck Cutaneous Squamous Cell Carcinoma with Skull Base Invasion.

    PubMed

    Cannon, Richard B; Dundar, Yusuf; Thomas, Andrew; Monroe, Marcus M; Buchmann, Luke O; Witt, Benjamin L; Sowder, Aleksandra M; Hunt, Jason P

    2017-04-01

    Objectives Skull base invasion from cutaneous squamous cell carcinoma (cSCC) via perineural spread affects survival and the rate of regional metastasis. Our objective is to investigate the factors associated with elective neck dissection (END) in this population and the survival difference with END compared with observation for patients with a cN0 neck. Study Design Case series with chart review. Setting Academic. Subjects and Methods Patients were treated surgically for head and neck cSCC with skull base invasion via perineural spread with a cN0 neck from 2004 to 2014. Clinicopathologic data were collected and analyzed. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Results Fifty-nine patients met inclusion criteria: 28 underwent an END and 31 underwent neck observation. Free tissue transfer reconstruction was significantly associated with END ( P < .001). Patients treated with an END had significantly improved 5-year DFS (57% and 32%, P = .042) and OS (60% and 37%, P = .036) compared with those who were observed and a significantly reduced rate of regional recurrence (9% and 37%, P = .024). The rate of occult nodal metastasis identified with END was 36% and is approximately equal to the regional failure rate of the neck observation group (37%). Conclusion END was more commonly used in cases requiring free tissue transfer. The use of END for head and neck cSCCs that have invaded the skull base is not routinely performed but was found to be associated with a survival advantage and reduced regional recurrence rate.

  15. Megavoltage computed tomography image-based low-dose rate intracavitary brachytherapy planning for cervical carcinoma.

    PubMed

    Wagner, Thomas H; Langen, Katja M; Meeks, Sanford L; Willoughby, Twyla R; Zeidan, Omar A; Staton, Robert J; Shah, Amish P; Manon, Rafael R; Kupelian, Patrick A

    2009-04-01

    Initial results of megavoltage computed tomography (MVCT) brachytherapy treatment planning are presented, using a commercially available helical tomotherapy treatment unit and standard low dose rate (LDR) brachytherapy applicators used for treatment of cervical carcinoma. The accuracy of MVCT imaging techniques, and dosimetric accuracy of the CT based plans were tested with in-house and commercially-available phantoms. Three dimensional (3D) dose distributions were computed and compared to the two dimensional (2D) dosimetry results. Minimal doses received by the 2 cm3 of bladder and rectum receiving the highest doses (D(B2cc) and D(R2cc), respectively) were computed from dose-volume histograms and compared to the doses computed for the standard ICRU bladder and rectal reference dose points. Phantom test objects in MVCT image sets were localized with sub-millimetric accuracy, and the accuracy of the MVCT-based dose calculation was verified. Fifteen brachytherapy insertions were also analyzed. The ICRU rectal point dose did not differ significantly from D(R2cc) (p=0.749, mean difference was 24 cGy +/- 283 cGy). The ICRU bladder point dose was significantly lower than the D(B2cc) (p=0.024, mean difference was 291 cGy +/- 444 cGy). The median volumes of bladder and rectum receiving at least the corresponding ICRU reference point dose were 6.1 cm(3) and 2.0 cm(3), respectively. Our initial experience in using MVCT imaging for clinical LDR gynecological brachytherapy indicates that the MVCT images are of sufficient quality for use in 3D, MVCT-based dose planning.

  16. Proteomic study of hepatocellular carcinoma using a novel modified aptamer-based array (SOMAscan™) platform.

    PubMed

    Qiao, Zhiwei; Pan, Xiaoqing; Parlayan, Cuneyd; Ojima, Hidenori; Kondo, Tadashi

    2017-04-01

    Vascular invasion is a pathological hallmark of hepatocellular carcinoma (HCC), associated with poor prognosis; it is strongly related to the early recurrence and poor survival after curative resection. In order to determine the proteomic backgrounds of HCC carcinogenesis and vascular invasion, we employed a novel modified aptamer-based array (SOMAscan) platform. SOMAscan is based on the Slow Off-rate Modified Aptamers (SOMAmers), which rely on the natural 3D folding of single-stranded DNA-based protein affinity reagents. Currently, the expression level of 1129 proteins can be assessed quantitatively. Correlation matrix analysis showed that the overall proteomic features captured by SOMAscan differ between tumor and non-tumor tissues. Non-tumor tissues were shown to have more homogeneous proteome backgrounds than tumor tissues. A comparative study identified 68 proteins with differential expression between tumor and non-tumor tissues, together with eight proteins associated with vascular invasion. Gene Ontology analysis showed that the extracellular space and extracellular region proteins were predominantly detected. Network analysis revealed the linkage of seven proteins, AKT1, MDM2, PTEN, FGF1, MAPK8, PRKCB, and FN1, which were categorized as the components of "Pathways in cancer" in pathway analysis. The results of SOMAscan analysis were not concordant with those obtained by western blotting; only the determined FN1 levels were concordant between the two platforms. We demonstrated that the proteome captured by SOMAscan includes the proteins relevant to carcinogenesis and vascular invasion in HCC. The identified proteins may serve as candidates for the future studies of disease mechanisms and clinical applications.

  17. Ameloblastic fibroma: a review of published studies with special reference to its nature and biological behavior.

    PubMed

    Chen, Yan; Wang, Jing-Ming; Li, Tie-Jun

    2007-11-01

    To further elucidate confusions with respect to the nature and biological behavior of ameloblastic fibroma (AF), available English-language literature since its first description in 1891 was reviewed. A total number of 123 cases with well-documented follow-up data were retrieved to evaluate various clinical, pathological and behavioral aspects of this tumor. AF tends to occur in the first two decades (89/123; 72.4%), but patients older than 22 years are not uncommon (30 cases). An overall recurrence rate of 33.3% (41 cases) is identified in reported cases who were treated by conservative (91.5%) and radical (8.5%) methods. Malignant transformation is evident in 14 recurrent tumors with an overall transformation rate of 11.4%. These data support the view that majority of AFs are true neoplasms. However, a small number of AFs occurring in childhood may represent the primitive stage of a developing odontoma, as three of the reported recurrent AFs do show further maturation with formation of dental hard tissues. A significantly longer recurrence-free survival was noted in patients treated by radical procedures in comparison to those treated by conservative methods and the age of patients at the first presentation was significantly related to malignant transformation of AF. As we are unable, at present, to differentiate a hamartomatous lesion from a neoplasm among this group of lesions merely on histologic grounds, age of the patients should be an important consideration when choosing therapeutic methods. Radical surgery should not be employed for the treatment of AFs in young people.

  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. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Prediction of the invasion depth of superficial squamous cell carcinoma based on microvessel morphology: magnifying endoscopic classification of the Japan Esophageal Society.

    PubMed

    Oyama, Tsuneo; Inoue, Haruhiro; Arima, Miwako; Momma, Kumiko; Omori, Tai; Ishihara, Ryu; Hirasawa, Dai; Takeuchi, Manabu; Tomori, Akihisa; Goda, Kenichi

    2017-01-01

    Predicting invasion depth of superficial esophageal squamous cell carcinoma is crucial in determining the precise indication for endoscopic resection because the rate of lymph node metastasis increases in proportion to the invasion depth of the carcinoma. Previous studies have shown a close relationship between microvascular patterns observed by Narrow Band Imaging magnifying endoscopy and invasion depth of the superficial carcinoma. Thus, the Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. We conducted a prospective study to evaluate the diagnostic values of type B vessels in the pretreatment estimation of invasion depth of superficial esophageal squamous cell carcinomas utilizing JES classification, the criteria of which are based on the degree of irregularity in the microvascular morphology. Type A microvessels corresponded to noncancerous lesions and lack severe irregularity; type B, to cancerous lesions, and exhibit severe irregularity. Type B vessels were subclassified into B1, B2, and B3, diagnostic criteria for T1a-EP or T1a-LPM, T1a-MM or T1b-SM1, and T1b-SM2 tumors, respectively. We enrolled 211 patients with superficial esophageal squamous cell carcinoma. The overall accuracy of type B microvessels in estimating tumor invasion depth was 90.5 %. We propose that the newly developed JES magnifying endoscopic classification is useful in estimating the invasion depth of superficial esophageal squamous cell carcinoma.

  20. LINAC- Based radiosurgery for melanoma, sarcoma and renal cell carcinoma brain metastases.

    PubMed

    Maranzano, Ernesto; Casale, Michelina; Rispoli, Rossella; Trippa, Fabio; Draghini, Lorena; Arcidiacono, Fabio; Carletti, Sandro; Anselmo, Paola

    2016-09-07

    To report response, overall survival (OS) and toxicity in patients with radioresistant brain metastases (BM) treated with radiosurgery (SRS). Patients with renal cell carcinoma, melanoma and sarcoma with one to four brain metastases received SRS without whole brain radiotherapy. 50 patients with 77 BM were treated. 46 (92%) patients with 71 BM were evaluable. Median follow-up was 67 months and median OS 11.8 months. At the time of analysis all patients had died. Brain control was conditioned by response to SRS (P<0.0001), while OS by histology (renal cell carcinoma versus melanoma and sarcoma) (P=0.04) and status of the tumour outside the brain (P=0.05). Treatment was well tolerated without more than grade 2 acute toxicity. Treatment of BM from radioresistant tumors with SRS assures good brain control and OS with low toxicity. Our data suggest a better prognosis associated to renal cell carcinoma histology.

  1. Risks of different skin tumor combinations after a first melanoma, squamous cell carcinoma and basal cell carcinoma in Dutch population based cohorts: 1989 - 2009.

    PubMed

    van der Leest, R J T; Hollestein, L M; Liu, L; Nijsten, T; de Vries, E

    2017-09-12

    Skin cancer patients are primarily at increased risk of developing subsequent skin cancers of the same type. Shared risk factors might also increase the occurrence of a different type of subsequent skin cancer. To investigate risks of different skin tumor combinations after a first melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). All melanoma and SCC patients included in the national Netherlands Cancer Registry (NCR) and all BCC patients included in the regional Eindhoven Cancer Registry (ECR) between 1989 and 2009 were followed until diagnosis of a subsequent different skin cancer (melanoma, SCC or BCC), date of death or end of study. Cumulative risks, Standardized Incidence Ratios (SIR) and Absolute Excess Risks (AER) of subsequent skin cancers were calculated. A total of 50,510 melanoma patients and 64,054 patients with a SCC of the skin were included (national data NCR). The regional data of the ECR consisted of 5,776 melanoma patients, 5,749 SCC patients and 41,485 BCC patients. The 21-year cumulative risk for a subsequent melanoma after a first SCC or BCC was respectively 1.7% and 1.3% for males and 1.3% and 1.2% for females; SCC after melanoma or BCC was 4.6% and 9.3% (males) and 2.6% and 4.1% (females); BCC after melanoma or SCC was respectively 13.2% and 27.8% (males) and 14.9% and 21.1% (females). SIRs and AERs remained elevated up to 21 years after the first melanoma, SCC or BCC. This large population based study investigating risks of developing a different subsequent cutaneous malignancy showed high cumulative risks of mainly KC and markedly increased relative and absolute risks of all tumor combinations. These estimates confirm a common carcinogenesis and can serve as a base for follow-up guidelines and patient education aiming for an early detection of the subsequent cancers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Treatment and survival of patients with insular thyroid carcinoma: 508 cases from the National Cancer Data Base.

    PubMed

    Pezzi, Todd A; Sandulache, Vlad C; Pezzi, Christopher M; Turkeltaub, Ashley E; Feng, Lei; Cabanillas, Maria E; Williams, Michelle D; Lai, Stephen Y

    2016-06-01

    Insular thyroid carcinoma (ITC) is a rare but aggressive thyroid malignancy. Patients with ITC (n = 508) reported to the National Cancer Data Base from 1998 to 2012 were evaluated for patient, tumor, and treatment characteristics and outcomes. Compared to papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), patients with ITC cancer were older, more often were men, had larger tumors, were more likely to present with distant metastasis, were less likely to have an R0 resection, more likely to receive external beam radiation and chemotherapy, and had significantly worse survival. Multivariate Cox regression identified age >65 years (hazard ratio [HR] = 1.53), presence of at least 1 comorbidity (HR = 1.80), positive lymph nodes (HR = 1.67), the presence of metastasis (HR = 2.73), positive margins (HR = 2.48), and radioactive iodine therapy (HR = 0.63) as significant and independent predictors of survival in ITC. Treatment recommendations should incorporate the use of radioactive iodine after complete surgical resection and clearance of involved nodal basins. © 2016 Wiley Periodicals, Inc. Head Neck 38: 906-912, 2016. © 2016 Wiley Periodicals, Inc.

  3. EpCAM-selective elimination of carcinoma cells by a novel MAP-based cytolytic fusion protein.

    PubMed

    Hristodorov, Dmitrij; Amoury, Manal; Mladenov, Radoslav; Niesen, Judith; Arens, Katharina; Berges, Nina; Hein, Lea; Di Fiore, Stefano; Pham, Anh-Tuan; Huhn, Michael; Helfrich, Wijnand; Fischer, Rainer; Thepen, Theo; Barth, Stefan

    2014-09-01

    In normal epithelia, the epithelial cell adhesion molecule (EpCAM) expression is relatively low and only present at the basolateral cell surface. In contrast, EpCAM is aberrantly overexpressed in various human carcinomas. Therefore, EpCAM is considered to be a highly promising target for antibody-based cancer immunotherapy. Here, we present a new and fully human cytolytic fusion protein (CFP), designated "anti-EpCAM(scFv)-MAP," that is comprised of an EpCAM-specific antibody fragment (scFv) genetically fused to the microtubule-associated protein tau (MAP). Anti-EpCAM(scFv)-MAP shows potent EpCAM-restricted proapoptotic activity toward rapidly proliferating carcinoma cells. In vitro assays confirmed that treatment with anti-EpCAM(scFv)-MAP resulted in the colocalization and stabilization of microtubules, suggesting that this could be the potential mode of action. Dose-finding experiments indicated that anti-EpCAM(scFv)-MAP is well tolerated in mice. Using noninvasive far-red in vivo imaging in a tumor xenograft mouse model, we further demonstrated that anti-EpCAM(scFv)-MAP inhibited tumor growth in vivo. In conclusion, our data suggest that anti-EpCAM(scFv)-MAP may be of therapeutic value for the targeted elimination of EpCAM(+) carcinomas.

  4. A Novel Inflammation-Based Stage (I Stage) Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Li, Jian-Pei; Chen, Shu-Lin; Liu, Xiao-Min; He, Xia; Xing, Shan; Liu, Yi-Jun; Lin, Yue-Hao; Liu, Wan-Li

    2016-01-01

    Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222–3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based

  5. Comparative treatment planning on localized prostate carcinoma conformal photon- versus proton-based radiotherapy.

    PubMed

    Mock, Ulrike; Bogner, Joachim; Georg, Dietmar; Auberger, Thomas; Pötter, Richard

    2005-07-01

    To assess the potential benefit of proton-beam therapy in comparison to 3-D conformal photon therapy and photon- based intensity-modulated radiotherapy (IMRT) in prostate carcinoma for various stages of disease. In five patients a 3-D conformal proton-based (two lateral beams) irradiation technique was compared with 3-D conformal photon-beam radiotherapy (four-field box) and IMRT (seven beams). For each patient different target volumes (CTVs) were defined according to early, intermediate and advanced stages of disease: CTV I consisted of the prostate gland, CTV II encompassed prostate and basis of seminal vesicles, and CTV III the prostate and seminal vesicles. Corresponding planning target volumes PTV I-III were defined by uniformly adding a margin of 5 mm to CTV I-III. Dose-volume histograms (DVHs) were analyzed for the different PTVs and various organs at risk (OARs), i.e., rectal wall, bladder, both femoral heads. In addition, maximum and mean doses were derived for the various structures and irradiated non-target tissue volumes were compared for PTV I-III and the different irradiation techniques. Finally, dose conformity and target dose homogeneity were assessed. With photon- and proton-based radiotherapy techniques similar dose distributions were determined for PTV I-III: mean and maximum PTV dose values were between 99-104% and 102-107% of the normalized total doses (70 Gy), respectively. Conformity indices varied from 1.4 to 1.5 for the photon techniques, whereas for proton-beam radiotherapy values ranged from 1.1 to 1.4. Both the 3-D conformal and the IMRT photon treatment technique resulted in increased mean doses (approximately 40-80%) for OARs when compared to protons. With both photon techniques non-target tissue volumes were irradiated to higher doses (mean dose difference > or = 70%) compared to proton-beam radiotherapy. Differences occurred mainly at the low and medium dose levels, whereas in high dose levels similar values were obtained. In

  6. PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma

    PubMed Central

    Cai, Chenlei; Xie, Yuexia; Wu, liangliang; Chen, Xiaojing; Liu, Hongmei; Zhou, Yan; Zou, Hanbing; Liu, Dejun; Zhao, Yanan; Kong, Xianming; Liu, Peifeng

    2017-01-01

    Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo, to inhibit HCC progression. In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent LipofectamineTM2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC. PMID:28387375

  7. 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.

  8. Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma

    PubMed Central

    Su, Yu-Li; Hsieh, Meng-Che; Chiang, Po-Hui; Sung, Ming-Tse; Lan, Jui; Luo, Hao-Lun; Huang, Chun-Chieh; Huang, Cheng-Hua; Tang, Yeh; Rau, Kun-Ming

    2017-01-01

    Purpose We developed a novel inflammation-based model (NPS), which consisted of a neutrophil to lymphocyte ratio (NLR) and platelet count (PC), for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC). Materials and Methods We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS) by using Kaplan–Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS. Results In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001) or PC (P < .0001). The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001). Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20–2.24, P = .002). Conclusion The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS. PMID:28076369

  9. Reagentless amperometric immunosensors based on direct electrochemistry of horseradish peroxidase for determination of carcinoma antigen-125.

    PubMed

    Dai, Zong; Yan, Feng; Chen, Jin; Ju, Huangxian

    2003-10-15

    A novel strategy for immunoassay and the preparation of reagentless immunosensors was proposed. This strategy was based on the immobilization of antigen and the direct electrochemistry of horseradish peroxidase (HRP) that was labeled to an antibody. A reagentless immunosensor for carcinoma antigen-125 (CA 125) determination was developed. The immunosensor was prepared by immobilizing CA 125 with titania sol-gel on a glassy carbon electrode by the vapor deposition method. The incubation of the immunosensor in phosphate buffer solution (PBS) including HRP-labeled CA 125 antibody led to the formation of a HRP-modified surface. The immobilized HRP displayed its direct electrochemistry with a rate constant of 3.04 +/- 1.21 s(-1). With a competition mechanism, a differential pulse voltammetric determination method for CA 125 was established by the peak current decrease of the immobilized HRP. The current decrease resulted from the competitive binding of the CA 125 in sample solution and the immobilized CA 125 to the limited amount of HRP-labeled CA 125 antibody. Under optimal conditions, the current decrease was proportional to CA 125 concentration ranging from 2 to 14 units mL(-1) with a detection limit of 1.29 units mL(-1) at a current decrease by 10%. The CA 125 immunosensor showed good accuracy and acceptable precision and fabrication reproducibility with intraassay CVs of 8.7 and 5.5% at 8 and 14 units mL(-1) CA 125 concentrations, respectively, and interassay CV of 19.8% at 8 units mL(-1). The storage stability was acceptable in a pH 7.0 PBS at 4 degrees C for 15 days. The proposed method provided a new promising platform for clinical immunoassay.

  10. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

    PubMed

    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Simultaneous EGFR and VEGF Alterations in Non-Small Cell Lung Carcinoma Based on Tissue Microarrays

    PubMed Central

    Tsiambas, Evangelos; Stamatelopoulos, Athanasios; Karameris, Andreas; Panagiotou, Ioannis; Rigopoulos, Dimitrios; Chatzimichalis, Antonios; Bouros, Demosthenes; Patsouris, Efstratios

    2007-01-01

    Background: Epidermal growth factor receptor (EGFR) overexpression is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Furthermore, overactivation of vascular endothelial growth factor (VEGF) leads to increased angiogenesis implicated as an important factor in vascularization of those tumors. Patients and Methods: Using tissue microarray technology, forty-paraffin (n = 40) embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR and VEGF protein levels which were evaluated by the performance of computerized image analysis. EGFR gene amplification was studied by chromogenic in situ hybridization based on the use of EGFR gene and chromosome 7 centromeric probes. Results: EGFR overexpression was observed in 23/40 (57.5%) cases and was correlated to the stage of the tumors (p = 0.001), whereas VEGF was overexpressed in 35/40 (87.5%) cases and was correlated to the stage of the tumors (p = 0.005) and to the smoking history of the patients (p = 0.016). Statistical significance was assessed comparing the protein levels of EGFR and VEGF (p = 0.043, k = 0.846). EGFR gene amplification was identified in 2/40 (5%) cases demonstrating no association to its overall protein levels (p = 0.241), whereas chromosome 7 aneuploidy was detected in 7/40 (17.5%) cases correlating to smoking history of the patients (p = 0.013). Conclusions: A significant subset of NSCLC is characterized by EGFR and VEGF simultaneous overexpression and maybe this is the eligible target group for the application of combined anti-EGFR/VEGF targeted therapies at the basis of genetic deregulation (especially gene amplification for EGFR). PMID:19455247

  12. Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma.

    PubMed

    Haddad, Ahmed Q; Luo, Jun-Hang; Krabbe, Laura-Maria; Darwish, Oussama; Gayed, Bishoy; Youssef, Ramy; Kapur, Payal; Rakheja, Dinesh; Lotan, Yair; Sagalowsky, Arthur; Margulis, Vitaly

    2017-05-01

    To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  13. 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

  14. Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo.

    PubMed

    Anand, Sanjay; Honari, Golara; Hasan, Tayyaba; Elson, Paul; Maytin, Edward V

    2009-05-15

    To improve treatment efficacy and tumor cell selectivity of delta-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) via pretreatment of cells and tumors with methotrexate to enhance intracellular photosensitizer levels. Skin carcinoma cells, in vitro and in vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in vivo skin tumor models were preconditioned with methotrexate for 72 h and then incubated with ALA for 4 h. Changes in protoporphyrin IX (PpIX) levels and cell survival after light exposure were assessed. Methotrexate preconditioning of monolayer cultures preferentially increased intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy compared with PDT alone. Methotrexate enhancement of PpIX levels was achieved over a broad methotrexate concentration range (0.0003-1.0 mg/L; 0.6 nmol/L-2 mmol/L). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, approximately 4-fold increase in coproporphyrinogen oxidase and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, and filaggrin) were also selectively induced by methotrexate in carcinoma cells. In vivo relevance was established by showing that methotrexate preconditioning enhances PpIX accumulation in three models: (a) organotypic cultures of immortalized keratinocytes, (b) chemically induced skin tumors in mice; and (c) human A431 squamous cell tumors implanted subcutaneously in mice. Combination therapy using short-term exposure to low-dose methotrexate followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas.

  15. Adrenocortical carcinoma

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001663.htm Adrenocortical carcinoma To use the sharing features on this page, please enable JavaScript. Adrenocortical carcinoma (ACC) is a cancer of the adrenal glands . ...

  16. 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.

  17. A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma.

    PubMed

    Ji, Jianguang; Sundquist, Kristina; Sundquist, Jan

    2012-05-16

    Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma.

  18. Surgical treatment of basal cell carcinoma: an algorithm based on the literature*

    PubMed Central

    Luz, Flávio Barbosa; Ferron, Camila; Cardoso, Gilberto Perez

    2015-01-01

    Although basal cell carcinoma can be effectively managed through surgical excision, the most suitable surgical margins have not yet been fully determined. Furthermore, micrographic surgery is not readily available in many places around the world. A review of the literature regarding the surgical treatment of basal cell carcinoma was conducted in order to develop an algorithm for the surgical treatment of basal cell carcinoma that could help the choice of surgical technique and safety margins, considering the major factors that affect cure rates. Through this review, it was found that surgical margins of 4mm seem to be suitable for small, primary, well-defined basal cell carcinomas, although some good results can be achieved with smaller margins and the use of margin control surgical techniques. For treatment of high-risk and recurrent tumors, margins of 5-6 mm or margin control of the surgical excision is required. Previous treatment, histological subtype, site and size of the lesion should be considered in surgical planning because these factors have been proven to affect cure rates. Thus, considering these factors, the algorithm can be a useful tool, especially for places where micrographic surgery is not widely available. PMID:26131869

  19. Surgical treatment of basal cell carcinoma: an algorithm based on the literature.

    PubMed

    Luz, Flávio Barbosa; Ferron, Camila; Cardoso, Gilberto Perez

    2015-01-01

    Although basal cell carcinoma can be effectively managed through surgical excision, the most suitable surgical margins have not yet been fully determined. Furthermore, micrographic surgery is not readily available in many places around the world. A review of the literature regarding the surgical treatment of basal cell carcinoma was conducted in order to develop an algorithm for the surgical treatment of basal cell carcinoma that could help the choice of surgical technique and safety margins, considering the major factors that affect cure rates. Through this review, it was found that surgical margins of 4mm seem to be suitable for small, primary, well-defined basal cell carcinomas, although some good results can be achieved with smaller margins and the use of margin control surgical techniques. For treatment of high-risk and recurrent tumors, margins of 5-6 mm or margin control of the surgical excision is required. Previous treatment, histological subtype, site and size of the lesion should be considered in surgical planning because these factors have been proven to affect cure rates. Thus, considering these factors, the algorithm can be a useful tool, especially for places where micrographic surgery is not widely available.

  20. Intraoperative biopsy of the major cranial nerves in the surgical strategy for adenoid cystic carcinoma close to the skull base.

    PubMed

    Tarsitano, Achille; Pizzigallo, Angelo; Gessaroli, Manlio; Sturiale, Carmelo; Marchetti, Claudio

    2012-02-01

    Adenoid cystic carcinoma of the salivary glands has a propensity for perineural invasion, which could favor spread along the major cranial nerves, sometimes to the skull base and through the foramina to the brain parenchyma. This study evaluated the relationship between neural spread and relapse in the skull base. During surgery, we performed multiple biopsies with extemporaneous examination of the major nerves close to the tumor to guide the surgical resection. The percentage of actuarial local control at 5 years for patients with a positive named nerve and skull base infiltration was 12.5%, compared with 90.0% in patients who were named nerve-negative and without infiltration of the skull base (P = .001). Our study shows that local control of disease for patients who are named nerve-positive with skull base infiltration is significantly more complex compared with patients who are named nerve-negative without infiltration of the skull base. Copyright © 2012. Published by Mosby, Inc.

  1. How Hepatitis C Virus Leads to Hepatocellular Carcinoma: A Network-Based Study

    PubMed Central

    Poortahmasebi, Vahdat; Poorebrahim, Mansour; Najafi, Saeideh; Jazayeri, Seyed Mohammad; Alavian, Seyed Moayed; Arab, Seyed Shahriar; Ghavami, Saeid; Alavian, Seyed Ehsan; Rezaei Moghadam, Adel; Amiri, Mehdi

    2016-01-01

    Background: Hepatitis C virus (HCV) has been known as a major cause of hepatocellular carcinoma (HCC) worldwide. However, the distinct molecular mechanisms underlying the effects of HCV proteins on the HCC progression have remained unclear. Objectives: In the present study, we studied the possible role of HCV in the HCC initiation and invasion using topological analysis of protein-protein interaction (PPI) networks. Materials and Methods: After analysis with GEO2R, a PPI network of differentially expressed genes (DEGs) was constructed for both chronic HCV and HCC samples. The STRING and GeneMANIA databases were used to determine the putative interactions between DEGs. In parallel, the functional annotation of DEGs was performed using g: Profiler web tool. The topological analysis and network visualization was carried outperformed using Cytoscape software and the top hub genes were identified. We determined the hub genes-related miRNAs using miRTarBase server and reconstructed a miRNA-Hubgene network. Results: Based on the topological analysis of miRNA-Hubgene network, we identified the key hub miRNAs. In order to identify the most important common sub-network, we aligned two PPI networks using NETAL tool. The c-Jun gene was identified as the most important hub gene in both HCV and HCC networks. Furthermore, the hsa-miR-34a, hsa-miR-155, hsa-miR-24, hsa-miR-744 and hsa-miR-92a were recognized as the most important hub miRNAs with positive correlation in the chronic HCV and HCC samples. Functional annotation of differentially expressed miRNAs (DEMs) using the tool for annotations of human miRNAs (TAM) revealed that there is a considerable overlap between miRNA gene expression profiles of HCV-infected and HCC cells. Conclusions: Our results revealed the possible crucial genes and miRNAs involved in the initiation and progression of HCC cells infected with HCV. PMID:27148389

  2. Screening serum hepatocellular carcinoma-associated proteins by SELDI-based protein spectrum analysis

    PubMed Central

    Cui, Jie-Feng; Liu, Yin-Kun; Zhou, Hai-Jun; Kang, Xiao-Nan; Huang, Cheng; He, Yi-Feng; Tang, Zhao-You; Uemura, Toshimasa

    2008-01-01

    AIM: To find out potential serum hepatocellular carcinoma (HCC)-associated proteins with low molecular weight and low abundance by SELDI-based serum protein spectra analysis, that will have much application in the diagnosis or differentiated diagnosis of HCC, as well as giving a better understanding of the mechanism of hepato-carcinogenesis. METHODS: Total serum samples were collected with informed consent from 81 HCC patients with HBV(+)/cirrhosis(+), 36 cirrhosis patients and 43 chronic hepatitis B patients. Serum protein fingerprint profiles were first generated by selected WCX2 protein chip capture integrating with SELDI-TOF-MS, then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard. Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra, some protein peaks with significant difference between HCC and cirrhosis or chronic hepatitis B were found. RESULTS: One hundred and twenty-eight serum protein peaks between 2000 and 30 000Da were identified under the condition of signal-to-noise > 5 and minimum threshold for cluster > 20%. Eighty-seven of these proteins were showed significant differences in intensity between HCC and cirrhosis (P < 0.05). Of the above differential proteins, 45 proteins had changes greater than two-fold, including 15 upregulated proteins and 30 downregulated proteins in HCC serum. Between HCC and chronic hepatitis B, 9 of 52 differential proteins (P < 0.05) had intensities of more than two-fold, including 2 upregulated proteins and 7 downregulated proteins in HCC serum. Between cirrhosis and chronic hepatitis B, 28 of 79 significant differential proteins (P < 0.05) changes greater than two-fold in intensity, including 17 upregulated proteins and 11 downregulated proteins in cirrhosis serum. For the analysis of these leading differential proteins in subtraction difference mode among three diseases, the five common downregulated proteins in HCC serum (M/Z 2870

  3. Screening serum hepatocellular carcinoma-associated proteins by SELDI-based protein spectrum analysis.

    PubMed

    Cui, Jie-Feng; Liu, Yin-Kun; Zhou, Hai-Jun; Kang, Xiao-Nan; Huang, Cheng; He, Yi-Feng; Tang, Zhao-You; Uemura, Toshimasa

    2008-02-28

    To find out potential serum hepatocellular carcinoma (HCC)-associated proteins with low molecular weight and low abundance by SELDI-based serum protein spectra analysis, that will have much application in the diagnosis or differentiated diagnosis of HCC, as well as giving a better understanding of the mechanism of hepato-carcinogenesis. Total serum samples were collected with informed consent from 81 HCC patients with HBV(+)/cirrhosis(+), 36 cirrhosis patients and 43 chronic hepatitis B patients. Serum protein fingerprint profiles were first generated by selected WCX2 protein chip capture integrating with SELDI-TOF-MS, then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard. Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra, some protein peaks with significant difference between HCC and cirrhosis or chronic hepatitis B were found. One hundred and twenty-eight serum protein peaks between 2000 and 30000 Da were identified under the condition of signal-to-noise > 5 and minimum threshold for cluster > 20%. Eighty-seven of these proteins were showed significant differences in intensity between HCC and cirrhosis (P < 0.05). Of the above differential proteins, 45 proteins had changes greater than two-fold, including 15 upregulated proteins and 30 downregulated proteins in HCC serum. Between HCC and chronic hepatitis B, 9 of 52 differential proteins (P < 0.05) had intensities of more than two-fold, including 2 upregulated proteins and 7 downregulated proteins in HCC serum. Between cirrhosis and chronic hepatitis B, 28 of 79 significant differential proteins (P < 0.05) changes greater than two-fold in intensity, including 17 upregulated proteins and 11 downregulated proteins in cirrhosis serum. For the analysis of these leading differential proteins in subtraction difference mode among three diseases, the five common downregulated proteins in HCC serum (M/Z 2870, 3941, 2688, 3165, 5483

  4. Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features.

    PubMed

    Sia, Daniela; Jiao, Yang; Martinez-Quetglas, Iris; Kuchuk, Olga; Villacorta-Martin, Carlos; Castro de Moura, Manuel; Putra, Juan; Camprecios, Genis; Bassaganyas, Laia; Akers, Nicholas; Losic, Bojan; Waxman, Samuel; Thung, Swan N; Mazzaferro, Vincenzo; Esteller, Manel; Friedman, Scott L; Schwartz, Myron; Villanueva, Augusto; Llovet, Josep M

    2017-09-01

    Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm. We then analyzed the gene expression pattern of inflammatory cells in HCC tumor samples. We correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples. We validated the correlation in a validation set of 728 tumor samples. Using data from 190 tumors in the Cancer Genome Atlas, we correlated immune cell gene expression profiles with numbers of chromosomal aberrations (based on single-nucleotide polymorphism array) and mutations (exome sequence data). We found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations. We called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 that mediate immunosuppression. We did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other HCCs. In an analysis of HCC samples from 956 patients, we found almost 25% to express markers of an inflammatory response. We identified 2 subclasses

  5. Genus beta human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study.

    PubMed

    Karagas, Margaret R; Waterboer, Tim; Li, Zhongze; Nelson, Heather H; Michael, Kristina M; Bavinck, Jan Nico Bouwes; Perry, Ann E; Spencer, Steven K; Daling, Janet; Green, Adele C; Pawlita, Michael

    2010-07-08

    To investigate the association between genus beta human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population. Population based case-control study. New Hampshire, USA. 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus beta human papillomaviruses by multiplex serology. Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to beta human papillomaviruses. Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual beta human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of beta types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous)=0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55). These findings support a relation between genus beta human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression.

  6. 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

  7. Active angiogenesis in metastatic renal cell carcinoma predicts clinical benefit to sunitinib-based therapy

    PubMed Central

    del Puerto-Nevado, L; Rojo, F; Zazo, S; Caramés, C; Rubio, G; Vega, R; Chamizo, C; Casado, V; Martínez-Useros, J; Rincón, R; Rodríguez-Remírez, M; Borrero-Palacios, A; Cristóbal, I; Madoz-Gúrpide, J; Aguilera, O; García-Foncillas, J

    2014-01-01

    Background: Sunitinib represents a widely used therapy for metastatic renal cell carcinoma patients. Even so, there is a group of patients who show toxicity without clinical benefit. In this work, we have analysed pivotal molecular targets involved in angiogenesis (vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (KDR), phosphorylated (p)KDR and microvascular density (MVD)) to test their potential value as predictive biomarkers of clinical benefit in sunitinib-treated renal cell carcinoma patients. Methods: Vascular endothelial growth factor-A, KDR and pKDR-Y1775 expression as well as CD31, for MVD visualisation, were determined by immunohistochemistry in 48 renal cell carcinoma patients, including 23 metastatic cases treated with sunitinib. Threshold was defined for each biomarker, and univariate and multivariate analyses for progression-free survival (PFS) and overall survival (OS) were carried out. Results: The HistoScore mean value obtained for VEGF-A was 121.6 (range, 10–300); for KDR 258.5 (range, 150–300); for pKDR-Y1775 10.8 (range, 0–65) and the mean value of CD31-positive structures for MVD visualisation was 49 (range, 10–126). Statistical differences for PFS (P=0.01) and OS (P=0.007) were observed for pKDR-Y1775 in sunitinib-treated patients. Importantly, pKDR-Y1775 expression remained significant after multivariate Cox analysis for PFS (P=0.01; HR: 5.35, 95% CI, 1.49–19.13) and for OS (P=0.02; HR: 5.13, 95% CI, 1.25–21.05). Conclusions: Our results suggest that the expression of phosphorylated (i.e., activated) KDR in tumour stroma might be used as predictive biomarker for the clinical outcome in renal cell carcinoma first-line sunitinib-treated patients. PMID:24786599

  8. Bowen's disease (squamous cell carcinoma in situ) in Kauai, Hawaii. A population-based incidence report.

    PubMed

    Reizner, G T; Chuang, T Y; Elpern, D J; Stone, J L; Farmer, E R

    1994-10-01

    The incidence of Bowen's disease (squamous cell carcinoma in situ) is rarely investigated. Our purpose was to report the incidence of Bowen's disease in a defined Caucasian population in Kauai, Hawaii. We conducted a prospective 5-year population study. We found 71 Caucasian residents, 44 men and 27 women, who had an initial episode of Bowen's disease during the 5-year period. The average annual incidence rate per 100,000 Caucasian residents of Kauai, standardized to the 1980 U.S. Caucasian population, was 174 for men and 115 for women, with a combined rate of 142. The incidence increased in older age groups. The mean age of the patients was 65.2 years. The most common anatomic site was the extremities. Subsequent Bowen's disease occurred in eight patients (11.3%). Recurrence after treatment developed in only one patient (1.4%). Twenty-six patients (36.6%) had concurrent skin cancers, either basal cell carcinoma or squamous cell carcinoma, or both. There was no increased incidence of internal malignancy. The incidence of Bowen's disease is high in Caucasian residents of Kauai and is 10 times higher than that reported from a northern Midwestern community. Kauai's intense ambient UV light and greater opportunity for year-round outdoor activities likely contributes to this higher rate.

  9. 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

  10. Label-free monitoring of colorectal adenoma-carcinoma sequence based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Chen, J. X.; Li, H. S.; Chen, Z. F.; Feng, C. Y.; Yang, Y. H.; Jiang, W. Z.; Guan, G. X.; Zhu, X. Q.; Zhuo, S. M.; Xu, J.

    2014-06-01

    The monitoring and evaluation of colorectal adenoma-carcinoma sequence during endoscopy are important for endoscopic resection of precursor lesions to disrupt the adenoma-carcinoma sequence and halt progression to invasive neoplastic disease. In this study, multiphoton microscopy (MPM) was used to identify different stages during the development of colorectal adenocarcinoma including adenoma with low-grade and high-grade dysplasia, and adenocarcinoma invading the submucosa. It was found that by combining two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging, MPM can reveal the morphological changes of the epithelial cells and glands, identify the invasive position and depth of atypical glands and quantitatively describe the change of the cellular nucleus and the nuclear-to-cytoplasmic ratio during the stepwise progression of colorectal adenocarcinoma. These are important pathological findings for pathologists when diagnosing colorectal lesions. With the advancement of a compact and flexible multiphoton endoscope for in vivo imaging and clinical applications, MPM has the potential to provide immediate histological diagnosis for the monitoring and evaluation of the colorectal adenoma-carcinoma sequence during endoscopy.

  11. [Influence of clinical and pathomorphological parameters on prognosis in colon carcinoma and rectal carcinoma].

    PubMed

    Xu, Fang-ying; Di, Mei-juan; Dong, Jian-kang; Wang, Feng-juan; Jin, Yi-sen; Zhu, Yi-min; Lai, Mao-de

    2006-05-01

    To investigate the effects of clinical and pathomorphological parameters on the prognosis of colon carcinoma and rectal carcinoma. Univariate and multivariate COX proportional hazard models were used to study the effects of the clinical and pathomorphological factors on the prognosis in 101 cases of colon carcinoma, 219 of rectal carcinoma and 137 of rectal carcinoma under curative resections. By using univariate analysis, we identified that lymph node metastasis and distant metastasis were the common prognostic factors for both colon carcinoma and rectal carcinoma. Smoking, deep infiltration, chemotherapy and serum albumin concentration were the uncertain prognostic factors for colon carcinoma. Signet-ring cell carcinoma, larger tumor size (>6 cm), deep infiltration, lack of radical surgery, and advanced TNM stage were the exclusive adverse prognostic factors for rectal carcinoma. Further studies showed that the adverse prognostic factors for the rectal carcinoma under curative resection included deep infiltration, lymph node metastasis, vessel invasion, less of peritumoral lymphocyte infiltration, lack of Crohn's like reactivity, high level of tumor budding, advanced TNM stage and positive urine glucose. By using multivariate analysis based on a COX proportional hazard model, it was identified that smoking, lymph node metastasis and serum albumin concentration were independent prognostic factors for colon carcinoma; advanced TNM stage, distant metastasis and palliative surgery for rectal carcinoma; and vessel invasion, lymph node metastasis and urine glucose for rectal carcinoma under curative resections. The various clinical and pathomorphological parameters show different prognostic value for colon carcinoma, rectal carcinoma and rectal carcinoma under curative resections.

  12. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

    PubMed

    Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

    2008-11-01

    Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

  13. Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma

    PubMed Central

    Lv, Yanhong; Zheng, Jinhua; Zhou, Qi; Jia, Limin; Wang, Chunying; Liu, Nian; Zhao, Hong; Ji, Hang; Li, Baoxin; Cao, Wenwu

    2017-01-01

    Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3–4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53. PMID:28102324

  14. A Case of Ameloblastic Fibroodontoma Extending Maxillary Sinus with Erupted Tooth: Is Transcanine Approach with Alveolectomy Feasible?

    PubMed Central

    Ecevit, Mustafa Cenk; Sarıoğlu, Sülen; Sütay, Semih

    2016-01-01

    Ameloblastic fibroodontoma (AFO) is a rare entity of mixed odontogenic tumors and frequently arises from posterior portion of the maxilla or mandible in first two decades of life. Herein, a 35-year-old woman with a noncontributory medical history who presented with a progressive left maxillary toothache, left maxillary first molar tooth mobility, and swelling in the left maxillary molar area for the last 2 months was reported. Radiologically, a tumor that originated from periapical area of the second mature molar teeth of maxilla was seen and additively unerupted tooth was not detected. The histopathologic examination revealed AFO. The patient is disease-free for five years after treated with limited segmental alveolectomy combining with Caldwell-Luc procedure. PMID:27891277

  15. Extensive ameloblastic fibroma in an adolescent patient: a case report with a follow-up of 4 years.

    PubMed

    Pitak-Arnnop, Poramate; Chaine, André; Dhanuthai, Kittipong; Bertrand, Jacques-Charles; Bertolus, Chloé

    2009-07-01

    Ameloblastic fibroma (AF) is a rare odontogenic tumour of the jaw which usually occurs in the first 2 decades of life. The common clinical manifestation is a slow-growing swelling. We report a case of a 16-year-old male patient presenting with extensive AF of the mandible. He underwent a conservative enucleation. The tumour recurred 2 years after the initial surgery, requiring the second enucleation. The patient has continued to be followed closely and has been disease-free for 4 years. Recent evidence suggests that the recurrent rate of AF is relatively high, and malignant transformation of AF may occur after recurrences or multiple surgeries. A conservative treatment approach with close surveillance is recommended. Anatomical limitations should be taken into account, especially when enucleation of AF in the posterior portion of the jaw is performed. Current surgical pathologic issues of the tumour are also discussed.

  16. 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

  17. Extensive Ameloblastic Fibroma in an Adolescent Patient: A Case Report with a Follow-Up of 4 Years

    PubMed Central

    Pitak-Arnnop, Poramate; Chaine, André; Dhanuthai, Kittipong; Bertrand, Jacques-Charles; Bertolus, Chloé

    2009-01-01

    Ameloblastic fibroma (AF) is a rare odontogenic tumour of the jaw which usually occurs in the first 2 decades of life. The common clinical manifestation is a slow-growing swelling. We report a case of a 16-year-old male patient presenting with extensive AF of the mandible. He underwent a conservative enucleation. The tumour recurred 2 years after the initial surgery, requiring the second enucleation. The patient has continued to be followed closely and has been disease-free for 4 years. Recent evidence suggests that the recurrent rate of AF is relatively high, and malignant transformation of AF may occur after recurrences or multiple surgeries. A conservative treatment approach with close surveillance is recommended. Anatomical limitations should be taken into account, especially when enucleation of AF in the posterior portion of the jaw is performed. Current surgical pathologic issues of the tumour are also discussed. PMID:19756198

  18. Enamel defects and ameloblast-specific expression in Enam knock-out/lacz knock-in mice.

    PubMed

    Hu, Jan C-C; Hu, Yuanyuan; Smith, Charles E; McKee, Marc D; Wright, J Timothy; Yamakoshi, Yasuo; Papagerakis, Petros; Hunter, Graeme K; Feng, Jerry Q; Yamakoshi, Fumiko; Simmer, James P

    2008-04-18

    Enamelin is critical for proper dental enamel formation, and defects in the human enamelin gene cause autosomal dominant amelogenesis imperfecta. We used gene targeting to generate a knock-in mouse carrying a null allele of enamelin (Enam) that has a lacZ reporter gene replacing the Enam translation initiation site and gene sequences through exon 7. Correct targeting of the transgene was confirmed by Southern blotting and PCR analyses. No enamelin protein could be detected by Western blotting in the Enam-null mice. Histochemical 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (X-gal) staining demonstrated ameloblast-specific expression of enamelin. The enamel of the Enam(+/-) mice was nearly normal in the maxillary incisors, but the mandibular incisors were discolored and tended to wear rapidly where they contacted the maxillary incisors. The Enam(-/-) mice showed no true enamel. Radiography, microcomputed tomography, and light and scanning electron microscopy were used to document changes in the enamel of Enam(-/-) mice but did not discern any perturbations of bone, dentin, or any other tissue besides the enamel layer. Although a thick layer of enamel proteins covered normal-appearing dentin of unerupted teeth, von Kossa staining revealed almost a complete absence of mineral formation in this protein layer. However, a thin, highly irregular, mineralized crust covered the dentin on erupted teeth, apparently arising from the formation and fusion of small mineralization foci (calcospherites) in the deeper part of the accumulated enamel protein layer. These results demonstrate ameloblast-specific expression of enamelin and reveal that enamelin is essential for proper enamel matrix organization and mineralization.

  19. Metastatic small cell carcinoma of the prostate: Population-based analysis of patient characteristics and treatment paradigms.

    PubMed

    Cohen, Andrew; Richards, Kyle A; Patel, Sanjay; Weiner, Adam; Eggener, Scott E; Szmulewitz, Russell Z

    2015-02-01

    Small cell carcinoma of the prostate is a rare malignancy comprising<1% of prostate cancers. Little is known about population-based treatment patterns for metastatic small cell carcinoma of the prostate. We evaluated clinical characteristics, treatment patterns, and survival outcomes. Using the National Cancer Database, we identified patients between 1998 and 2011 diagnosed with pure small cell carcinoma of the prostate as their only malignancy who presented with nodal involvement or distant metastasis. Treatment information was available for 379 patients. Of them, 122 (32.5%) underwent chemotherapy (CT) alone, 25 (6.7%) received hormonal therapy (androgen-deprivation therapy) alone, 10 (2.7%) underwent radiation therapy alone, 3 (1%) underwent radical prostatectomy, and 167 (44.4%) underwent combination therapy. The 1- and 3-year survival rates were 35.3% and 4.4%, respectively. Those receiving any CT as part of their treatment had a median survival of 9.3 vs. 3.2 months for those not receiving it (P<0.001). Those receiving CT, androgen-deprivation therapy, and radiation had a median survival of 15.1 vs. 7 months for those receiving CT alone (P<0.001). On multivariable analysis (controlling for age, Charlson comorbidity index, extent of metastasis, prostate-specific antigen level, and type of treatment), older age (hazard ratio [HR] = 3.87; 95% CI: 1.41-9.34; P = 0.007) and distant metastatic disease (HR = 7.17; 95% CI: 1.62-31.8; P = 0.010) increased risk of death, whereas receipt of CT (HR = 0.15; 95% CI: 0.05-0.44; P = 0.001) decreased risk of death. Men presenting with metastatic small cell carcinoma of the prostate have poor overall survival. Older patients and those presenting with distant metastases have an increased risk of death. It appears that patients receiving CT experience a modest survival benefit. The role of hormonal therapy in this population remains unclear. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. [Bronchoalveolar carcinoma].

    PubMed

    Wislez, Marie; Cadranel, Jacques; Milleron, Bernard

    2003-04-01

    Bronchoalveolar carcinoma is one of the four histologic subtypes of adenocarcinoma and its incidence is increasing. It grows in a lepidic fashion along the alveolar septa without invasive growth. The lack of invasive growth is an essential criterion based on data indicating that patients may be curable by surgical resection. The revised definition seems to be suitable for its solitary nodular form but less for multifocal or pneumonic-type form. High-resolution lung CT-scan is necessary to evaluate pulmonary involvement because of the high frequency of multifocal disease at initial presentation and because of the presence of ground glass opacity that could be one of the first manifestation of cancer bronchiolo-alvéolaireon CT. Therapeutic management does not differ from the one of non small cell lung cancer. Solitary nodules are treated by surgical resection with a good prognosis while multifocal and/or pneumonic forms are treated by systemic chemotherapy with a worse prognosis.

  1. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

    PubMed

    Li, Mengjiao; Li, Haoran; Liu, Fei; Bi, Rui; Tu, Xiaoyu; Chen, Lihua; Ye, Shuang; Cheng, Xi

    2017-02-10

    It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar

  2. Determination of deep surgical margin based on anatomical architecture for local control of squamous cell carcinoma of the buccal mucosa.

    PubMed

    Ota, Yoshihide; Aoki, Takayuki; Karakida, Kazunari; Otsuru, Mitsunobu; Kurabayashi, Hirotaka; Sasaki, Masashi; Nakamura, Naoya; Kajiwara, Hiroshi

    2009-07-01

    Of all oral squamous cell carcinomas, squamous cell carcinomas of the buccal mucosa (BSCC) are most associated with poorest prognosis. In particular, patients treated with surgery alone are reported to experience frequent local failures. This is considered to result from the surgeon's determination of the deep surgical margin for resection based on palpation alone when performing BSCC surgery. Therefore, an objective system for classifying the depth of invasion of a tumor appears to be necessary in order to improve the results of BSCC treatment. While current general practice is to treat based on tumor thickness, we would like to emphasize the importance of how far down the cheek wall layer the tumor has invaded. We performed surgery by classifying the depths of tumor invasion in relation to the buccinator. Depth of tumor invasion was assessed mainly using ultrasonography (US). The tumor was defined as D1 when it extended to the mucosal (m) and submucosal layers (sm). In these cases, the tumor was resected, while the buccinator was spared. The tumor was defined as D2 when it extended to the buccinator, but, based on US, muscle continuity was preserved, and the tumor was resected to include the buccinator and its overlying fascia. When the tumor had spread to the buccinator or invaded subcutaneous or cutaneous tissue it was classified as D3 and resection included the skin. The disease-specific survival rate of BSCC when treated based on our classification was 73.7% and the local control rate was 89.5%. These results are superior to those based on surgery alone and this therapeutic modality was considered to be useful.

  3. Analysis of the base excision repair genes MTH1, OGG1 and MUTYH in patients with squamous oral carcinomas.

    PubMed

    Görgens, Heike; Müller, Annegret; Krüger, Stefan; Kuhlisch, Eberhard; König, Inke R; Ziegler, Andreas; Schackert, Hans K; Eckelt, Uwe

    2007-09-01

    A number of environmental factors, such as tobacco and alcohol, have been implicated, through oxidative DNA damage, in the development of squamous cell carcinomas of the head and neck (SCCHN). Several pathways are involved in the repair of DNA lesions caused by oxidative stress, such as the base excision repair system (BER), which repairs mutation involving 8-oxoguanine and comprises the MUTYH, OGG1 and MTH1 genes. We analysed 29 patients, assessing germline polymorphisms or mutations in these genes by complete genomic sequencing of exons and adjacent intronic regions. Thirty healthy blood donors served as controls. No pathogenic germline mutations were identified. We found common and rare new variants in the coding and adjacent intronic regions. In summary, our data do not support a major role for MUTYH, OGG1 and MTH1 variants in the etiology of sporadic squamous oral/oropharyngeal carcinomas. This does not exclude the involvement of the three BER genes in the tumorigenesis of SCCHN through other mechanisms such as promotor hypermethylation, genomic rearrangements or mutations involving regulatory sequences.

  4. 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

  5. Active radar guides missile to its target: receptor-based targeted treatment of hepatocellular carcinoma by nanoparticulate systems.

    PubMed

    Yan, Jing-Jun; Liao, Jia-Zhi; Lin, Ju-Sheng; He, Xing-Xing

    2015-01-01

    Patients with hepatocellular carcinoma (HCC) usually present at advanced stages and do not benefit from surgical resection, so drug therapy should deserve a prominent place in unresectable HCC treatment. But chemotherapy agents, such as doxorubicin, cisplatin, and paclitaxel, frequently encounter important problems such as low specificity and non-selective biodistribution. Recently, the development of nanotechnology led to significant breakthroughs to overcome these problems. Decorating the surfaces of nanoparticulate-based drug carriers with homing devices has demonstrated its potential in concentrating chemotherapy agents specifically to HCC cells. In this paper, we reviewed the current status of active targeting strategies for nanoparticulate systems based on various receptors such as asialoglycoprotein receptor, transferrin receptor, epidermal growth factor receptor, folate receptor, integrin, and CD44, which are abundantly expressed on the surfaces of hepatocytes or liver cancer cells. Furthermore, we pointed out their merits and defects and provided theoretical references for further research.

  6. 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

  7. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

  8. 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.

  9. In vivo imaging of hepatocellular carcinoma using a glypican-3-binding peptide based probe

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Han, Zhihao; Zhang, Wancun; Qian, Zhiyu; Gu, Yueqing

    2017-02-01

    Hepatocellular carcinoma (HCC) has been the third most common cause of cancer-related death worldwide. Glypican-3 (GPC3) is a heparin sulfate proteoglycan linked to the cell membrane by a glycosyl-phosphatidylinositol anchor (GPI) and is expressed by 75% of all hepatocellular carcinomas but undetectable in healthy liver tissue or liver with focal lesions. What's more, GPC3 has been gradually applied in clinical applications as a specific indicator for the early detection and prognosis of HCC. As GPC3 can also regulate many pathways in HCC pathogenesis including Wnt, Hh and Yap signaling, it has been shown that GPC3 knockdown can inhibit HCC growth, reinforcing the important roles of GPC3 in HCC development. For HCC early detection, we designed a peptide targeting GPC3 that allows to establish a fluorescent dyes-labeled probe. Firstly, according to the structure of the GPC3 antibody GC33 and the positive peptide reported in the literature, we generated a peptide consisting of twelve amino acids named 12P that may bind to GPC3 with tight binding ability and specificity. In vitro testing, we utilized FCM and laser confocal microscopy to verify its specificity of targeting to the high expression cells of GPC3. What's more, we linked 12P with a near infrared dye to verify its in vivo targeting ability. All results indicated that 12P possessed potent binding capacity which could be used as a targeting module in GPC3 detection probe.

  10. Treatment of recurrent carcinoma at the base of the skull with carbon dioxide laser.

    PubMed

    Rontal, M; Rontal, E

    1983-10-01

    The extension of carcinoma to the cribriform plate is a poor prognostic finding. Two extremes of treatment approach have been advocated. On the one hand, patients may be abandoned to palliative chemotherapy. On the other hand, heroic and aggressive resections may be advocated including combined neurosurgical transdural and otolaryngologic facial-orbital resection. Armed with the surgical microscope and the CO2 laser there may be a place for a middle ground of therapy. We present our experience with recurrent tumor after full course radiation therapy and maxilloethmoidectomy. The biopsy proven recurrences were found at the cribriform plate but could not be shown to have crossed into the anterior cranial fossa by polytomography or high resolution CT scanning. The CO2 surgical laser delivered through the surgical microscope was used with repeated applications. Recurrent epidermoid carcinoma found to be confined to the nasal side of the cribriform plate can be controlled by careful microscopic stripping of soft tissue from the cribriform plate with a surgical laser.

  11. Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis.

    PubMed

    Hu, Ting-Zi; Huang, Li-Hua; Xu, Can-Xia; Liu, Xiao-Ming; Wang, Yu; Xiao, Jing; Zhou, Li; Luo, Ling; Jiang, Xiao-Xia

    2015-12-01

    Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPα were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma.

  12. Differentiating rectal carcinoma by an immunohistological analysis of carcinomas of pelvic organs based on the NCBI Literature Survey and the Human Protein Atlas database.

    PubMed

    Miura, Koh; Ishida, Kazuyuki; Fujibuchi, Wataru; Ito, Akihiro; Niikura, Hitoshi; Ogawa, Hitoshi; Sasaki, Iwao

    2012-06-01

    The treatments and prognoses of pelvic organ carcinomas differ, depending on whether the primary tumor originated in the rectum, urinary bladder, prostate, ovary, or uterus; therefore, it is essential to diagnose pathologically the primary origin and stages of these tumors. To establish the panels of immunohistochemical markers for differential diagnosis, we reviewed 91 of the NCBI articles on these topics and found that the results correlated closely with those of the public protein database, the Human Protein Atlas. The results revealed the panels of immunohistochemical markers for the differential diagnosis of rectal adenocarcinoma, in which [+] designates positivity in rectal adenocarcinoma and [-] designates negativity in rectal adenocarcinoma: from bladder adenocarcinoma, CDX2[+], VIL1[+], KRT7[-], THBD[-] and UPK3A[-]; from prostate adenocarcinoma, CDX2[+], VIL1[+], CEACAM5[+], KLK3(PSA)[-], ACPP(PAP)[-] and SLC45A3(prostein)[-]; and from ovarian mucinous adenocarcinoma, CEACAM5[+], VIL1[+], CDX2[+], KRT7[-] and MUC5AC[-]. The panels of markers distinguishing ovarian serous adenocarcinoma, cervical carcinoma, and endometrial adenocarcinoma were also represented. Such a comprehensive review on the differential diagnosis of carcinomas of pelvic organs has not been reported before. Thus, much information has been accumulated in public databases to provide an invaluable resource for clinicians and researchers.

  13. Childhood Carcinoma.

    PubMed

    Vargas, Sara O

    2010-09-01

    Carcinoma in children differs from that occurring in adults. It is far rarer and represents only a small fraction of all pediatric cancer diagnoses. Pediatric sarcomas were among the first tumors in which recurrent chromosomal aberrations were discovered. Once defined, these recurrent aberrations, many of them translocations, became incorporated into the pathologist's diagnostic armamentarium. In the past several years, defining chromosomal rearrangements have been identified in pediatric carcinomas as well, and this has become a new frontier in pathologic diagnosis. This article provides an overview of pediatric carcinoma as well as a detailed review of selected types of carcinoma that in particular can present diagnostic difficulty to the practicing pathologist and illustrate new and emerging concepts in pediatric carcinoma.

  14. [Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

    PubMed

    Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1988-06-01

    We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

  15. CT-diagnosed severe skull base bone destruction predicts distant bone metastasis in early N-stage nasopharyngeal carcinoma

    PubMed Central

    Yi, Wei; Liu, Zhi-Gang; Li, Xian; Tang, Jiao; Jiang, Chang-Bin; Hu, Jing-Ye; Tu, Zi-Wei; Wang, Hui; Niu, Dao-Li; Xia, Yun-Fei

    2016-01-01

    Bone metastasis is the most frequent type of distant metastasis in nasopharyngeal carcinoma (NPC). In this study, we investigated the correlation between the skull base bone destruction and the distant bone metastasis in patients with NPC. A total of 449 cases with NPC who were diagnosed and had definitive radiotherapy from 2001 to 2006 were enrolled in this study. The skull base bone destruction was diagnosed by computed tomography (CT) in all cases, and 191 patients also underwent magnetic resonance imaging scan. Kaplan–Meier method was adopted to perform the univariate analysis; Cox regression model was used to perform multivariate analysis to determine whether the skull base bone destruction when diagnosed by CT was an independent impact factor of the distant bone metastases. The group with skull base bone destruction had a distant bone metastases rate of 9.0% (14/155), whereas the group without skull base bone destruction had rate of 4.1% (12/294). The multivariate analysis showed that the skull base bone destruction, when diagnosed by CT, was an independent impact factor of the distant bone metastases-free survival in the early N-staging cases, but was not an independent impact factor when diagnosed by MRI. The skull base bone destruction diagnosed by CT in patients with NPC had predictive value for the distant bone metastases, especially for the early N-staging cases. PMID:27895493

  16. 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

  17. Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

    PubMed Central

    Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

  18. [Continuous development of laparoscopic surgery for gastrointestinal carcinoma based on process optimization and technical innovation].

    PubMed

    Su, Xiangqian; Yang, Hong

    2014-08-01

    With process optimization and technical innovation, laparoscopic gastrointestinal surgery has evolved dramatically over the last two decades and provided important improvement in the contemporary surgical practice and patients' recovery. With the emergence of many new minimally invasive technologies, including total laparoscopic surgery, single-incision laparoscopic surgery, and natural orifice specimen extraction, patents with gastrointestinal carcinomas may experience less pain and have lower perioperative complications, but the exact efficacy remains to be proven. Large-scale international multi-centre randomized controlled trial data have revealed that laparoscopic colorectal surgery is safe both in terms of short-term perioperative outcomes and long-term oncological efficacy. However, the question whether there is an equivalent oncological outcome compared to the open approach in gastric cancer is still unanswered by now and needs to be proven by future studies.

  19. Optimal multivariate method for Raman spectroscopy based diagnosis of nasopharyngeal carcinoma

    NASA Astrophysics Data System (ADS)

    Chen, Bingling; Li, Shaoxin; Li, Jianghua; Guo, Zhouyi; Chen, Qiuyan; Mai, Haiqiang

    2013-12-01

    In this paper, we evaluated four kinds of classification algorithms on Raman spectra for nasopharyngeal carcinoma (NPC) diagnosis: Bayesian classification (BC), Linear discriminate analysis (LDA), Mahalanobis distance after the principal component analysis (PCA); as well the Genetic algorithm-LDA. A total of 225 Raman spectra were acquired from 120 tissue sites of 63 patients, in which 56 Raman spectra were from normal tissue, whereas 171 Raman spectra were from cancer nasopharyngeal tissue. The averaged Raman spectrum of NPC could be distinguished from that of the control group by the above multivariate analysis. Discrimination analysis of PCA-BC revealed that the highest sensitivity, specificity and overall accuracy of cancer diagnosis were 98% (1/56), 99% (1/171), and 99%, respectively. The results showed that Raman spectroscopy in combination with Bayesian classification had high enough sensitivity and specificity to accurately detect and diagnose NPC.

  20. High-dose rate brachytherapy for local recurrent adenoid cystic carcinoma of the tongue base following postoperative external beam radiotherapy

    PubMed Central

    Lee, Sun Young; Kim, Jung Soo; Kwon, Hyoung Cheol

    2016-01-01

    Adenoid cystic carcinoma is a rare neoplasm commonly originating from the minor salivary glands. The clinical findings typical of this tumor include slow growth, perineural invasion and high frequency of local recurrence. In this study, a patient presented with a tongue base lesion that was treated with surgical excision and additional postoperative external beam radiotherapy. However, local recurrence occurred 8 months after radiotherapy. If recurrence occurs after radiation therapy, total glossectomy should be considered. However, the patient refused re-operation and, considering the patient's age, brachytherapy was used to ensure organ preservation. Complete remission was achieved following brachytherapy, without serious side effects. There has been no progression of the lesion during a follow-up period of 2 years. PMID:27882233

  1. Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

    NASA Astrophysics Data System (ADS)

    Qiu, Sufang; Li, Chao; Lin, Jinyong; Xu, Yuanji; Lu, Jun; Huang, Qingting; Zou, Changyan; Chen, Chao; Xiao, Nanyang; Lin, Duo; Chen, Rong; Pan, Jianji; Feng, Shangyuan

    2016-12-01

    Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573 cm-1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

  2. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Bioluminescence-Based High-Throughput Screen Identifies Pharmacological Agents That Target Neurotransmitter Signaling in Small Cell Lung Carcinoma

    PubMed Central

    Improgo, Ma. Reina D.; Johnson, Christopher W.; Tapper, Andrew R.; Gardner, Paul D.

    2011-01-01

    Background Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative. Methods and Findings We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC1280 compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability. Conclusions The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development. PMID:21931655

  4. Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma.

    PubMed

    Chen, Ming-Huang; Yang, Wu-Lung R; Lin, Kuan-Ting; Liu, Chia-Hung; Liu, Yu-Wen; Huang, Kai-Wen; Chang, Peter Mu-Hsin; Lai, Jin-Mei; Hsu, Chun-Nan; Chao, Kun-Mao; Kao, Cheng-Yan; Huang, Chi-Ying F

    2011-01-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.

  5. Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms.

    PubMed

    Cheng, Na; Hui, Da-yang; Liu, Yong; Zhang, Na-na; Jiang, Ye; Han, Jing; Li, Hai-Gang; Ding, Yun-Gang; Du, Hong; Chen, Jian-Ning; Shao, Chun-Kui

    2015-04-01

    Gastric lymphoepithelioma-like carcinoma (LELC) is a rare entity that is closely associated with Epstein-Barr virus (EBV). However, the EBV latency pattern and genome polymorphisms in gastric LELC have not been systematically explored. The clinicopathological features, EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC in Guangzhou, southern China were investigated and compared with those of ordinary EBV-associated gastric carcinoma (EBVaGC) in the same area. Ten (1.42%) of 702 gastric carcinoma cases were identified as gastric LELC, in which eight (80%) cases were EBV-positive. The clinicopathological characteristics and EBV latency pattern of EBV-positive gastric LELC were similar to those of ordinary EBVaGC. In EBV genotype analysis, type A strain, type F, I, mut-W1/I, XhoI- and del-LMP1 variants were predominant among EBV-positive gastric LELCs, accounting for eight (100%), six (75%), eight (100%), seven (87.5%), five (62.5%) and six (75%) cases, respectively, which are similar to those in ordinary EBVaGC. For EBNA1 polymorphisms, the V-leu and P-ala subtypes were predominant in EBV-positive gastric LELC, which is different from the predominant V-val subtype in ordinary EBVaGC. EBV-positive gastric LELC has a favorable prognosis when compared to ordinary EBVaGC (median survival time 43.0 vs. 18.0 months). Gastric LELC is strongly associated with EBV and EBV-positive gastric LELC should be regarded as a special subtype of EBVaGC. This, to our best knowledge, is the first time in the world that the EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC are systematically revealed.

  6. 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.

  7. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.

    PubMed

    Graham, Rondell P; Vierkant, Robert A; Tillmans, Lori S; Wang, Alice H; Laird, Peter W; Weisenberger, Daniel J; Lynch, Charles F; French, Amy J; Slager, Susan L; Raissian, Yassaman; Garcia, Joaquin J; Kerr, Sarah E; Lee, Hee Eun; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul J; Smyrk, Thomas C

    2015-10-01

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P < 0.001), microsatellite stability (P = 0.005), KRAS mutation (P = 0.010), and on multivariate analysis with a > 2 times risk of cancer-specific death (hazard ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted κ of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

  8. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort

    PubMed Central

    Graham, Rondell P.; Vierkant, Robert A.; Tillmans, Lori S.; Wang, Alice H.; Laird, Peter W; Weisenberger, Daniel J.; Lynch, Charles F.; French, Amy J.; Slager, Susan L.; Raissian, Yassaman; Garcia, Joaquin J.; Kerr, Sarah E.; Lee, Hee Eun; Thibodeau, Stephen N.; Cerhan, James R.; Limburg, Paul J.; Smyrk, Thomas C.

    2015-01-01

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for “high” tumor budding, heterogeneity in study populations and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for “high” tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between two GI pathologists and a group of four general surgical pathologists. High budding (≥10 tumor buds in a 20× objective field) was present in 32% of cases, low budding in 46% and no budding in 22%. High tumor budding was associated with advanced pathologic stage (p<0.001), microsatellite stability (p=0.005), KRAS mutation (p=0.010) and on multivariate analysis with a greater than two times risk of cancer-specific death (HR=2.57 (1.27, 5.19)). After multivariate adjustment, via penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer –specific death. The interobserver agreement was good with weighted kappa of 0.70 for two GI pathologists over 121 random cases and 0.72 between all six pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports. PMID:26200097

  9. Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study

    NASA Astrophysics Data System (ADS)

    Delpueyo, Xana; Vilaseca, Meritxell; Royo, Santiago; Ares, Miguel; Rey-Barroso, Laura; Sanabria, Ferran; Puig, Susana; Pellacani, Giovanni; Noguero, Fernando; Solomita, Giuseppe; Bosch, Thierry

    2017-06-01

    This article proposes a multispectral system that uses the analysis of the spatial distribution of color and spectral features to improve the detection of skin cancer lesions, specifically melanomas and basal cell carcinomas. The system consists of a digital camera and light-emitting diodes of eight different wavelengths (414 to 995 nm). The parameters based on spectral features of the lesions such as reflectance and color, as well as others empirically computed using reflectance values, were calculated pixel-by-pixel from the images obtained. Statistical descriptors were calculated for every segmented lesion [mean (x˜), standard deviation (σ), minimum, and maximum]; descriptors based on the first-order statistics of the histogram [entropy (Ep), energy (En), and third central moment (μ3)] were also obtained. The study analyzed 429 pigmented and nonpigmented lesions: 290 nevi and 139 malignant (95 melanomas and 44 basal cell carcinomas), which were split into training and validation sets. Fifteen parameters were found to provide the best sensitivity (87.2% melanomas and 100% basal cell carcinomas) and specificity (54.5%). The results suggest that the extraction of textural information can contribute to the diagnosis of melanomas and basal cell carcinomas as a supporting tool to dermoscopy and confocal microscopy.

  10. Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study.

    PubMed

    Delpueyo, Xana; Vilaseca, Meritxell; Royo, Santiago; Ares, Miguel; Rey-Barroso, Laura; Sanabria, Ferran; Puig, Susana; Pellacani, Giovanni; Noguero, Fernando; Solomita, Giuseppe; Bosch, Thierry

    2017-06-01

    This article proposes a multispectral system that uses the analysis of the spatial distribution of color and spectral features to improve the detection of skin cancer lesions, specifically melanomas and basal cell carcinomas. The system consists of a digital camera and light-emitting diodes of eight different wavelengths (414 to 995 nm). The parameters based on spectral features of the lesions such as reflectance and color, as well as others empirically computed using reflectance values, were calculated pixel-by-pixel from the images obtained. Statistical descriptors were calculated for every segmented lesion [mean ( x ˜ ), standard deviation ( σ ), minimum, and maximum]; descriptors based on the first-order statistics of the histogram [entropy ( E p ), energy ( E n ), and third central moment ( μ 3 )] were also obtained. The study analyzed 429 pigmented and nonpigmented lesions: 290 nevi and 139 malignant (95 melanomas and 44 basal cell carcinomas), which were split into training and validation sets. Fifteen parameters were found to provide the best sensitivity (87.2% melanomas and 100% basal cell carcinomas) and specificity (54.5%). The results suggest that the extraction of textural information can contribute to the diagnosis of melanomas and basal cell carcinomas as a supporting tool to dermoscopy and confocal microscopy.

  11. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms

    PubMed Central

    2014-01-01

    Background Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas. Results Different models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8. Conclusions We anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors. PMID:25374611

  12. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms.

    PubMed

    Jagga, Zeenia; Gupta, Dinesh

    2014-01-01

    Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas. Different models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8. We anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors.

  13. 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

  14. 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.

  15. Metaplastic carcinoma of the breast: Treatment, results and prognostic factors based on international literature.

    PubMed

    Sanguinetti, Alessandro; Lucchini, Roberta; Santoprete, Stefano; Farabi, Raffaele; Fioriti, Lorella; Bistoni, Giovanni; Triola, Roberta; Avenia, Nicola

    2014-01-01

    Metaplastic carcinoma of the breast (MCB) is a rare form of cancer containing mixture of epithelial and mesenchymal elements in variable combinations. Few and conflicting clinical data are available in the literature addressing optimal treatment modalities, prognosis and outcome. A retrospective study was conducted to review all patients with MCB diagnosed and treated at Breast Unit of Azienda Ospedaliera "Santa Maria" Terni - Italy between 2001/2010. The aim is to describe patient's clinic pathologic features and to analyze treatment results. Six female patients were studied. The median age was 48 years (range 14/58). The median tumor size was 9 cm. (range 3/18 cm.). Two cases (33%) were identified as purely epithelial and 4 (67%) as mixed epithelial and mesenchymal metaplasia. Hormone receptors were positive in only 2 patients. Modified radical mastectomy performed in 3 patients and 5 underwent axillary node dissection. Adjuvant chemotherapy was given to all patients and postoperative radiotherapy to 4. Four patients relapsed with median time of relapse of 12 months. MCB is an aggressive form of breast cancer associated with poor outcome, high incidence of local recurrence and pulmonary metastases. The disease tends to be estrogen/progesterone receptor negative. Tumor size has an important impact on outcome. The best treatment approach is yet to be defined.

  16. Age-dependent association between sex and renal cell carcinoma mortality: a population-based analysis.

    PubMed

    Qu, Yuanyuan; Chen, Haitao; Gu, Weijie; Gu, Chengyuan; Zhang, Hailiang; Xu, Jianfeng; Zhu, Yao; Ye, Dingwei

    2015-03-17

    Research on sex differences in renal cancer-specific mortality (RCSM), which considered the sex effect to be constant throughout life, has yielded conflicting results. This study hypothesized the sex effect may be modified by age, which is a proxy for hormonal status. Data from the Surveillance, Epidemiology and End Results database (1988-2010) were used to identify 114,539 patients with renal cell carcinoma (RCC). The study cohort was divided into three age groups using cutoffs of 42 and 58 years, which represent the premenopausal and postmenopausal periods. The cumulative incidence function and competing risks analyses were used to examine the effect of covariates on RCSM and other-cause mortality (OCM). In premenopausal period, male sex was a significant predictor of poor RCSM for both localized (adjusted subdistribution hazard ratio [aSHR] = 1.63, P = 0.002) and advanced (aSHR = 1.20, P = 0.041) disease. In postmenopausal period, the sex disparity diminished (aSHR = 1.05, P = 0.16) and reversed (aSHR = 0.95, P = 0.017) in localized and advanced disease, respectively. On the contrary, similar trend was not found for OCM across all age groups. Our results demonstrated the sex effect on RCSM was strongly modified by age. These findings may aid in clinical practice and need further evaluation of underlying biological mechanisms.

  17. Multidisciplinary decision making in the management of hepatocellular carcinoma: A hospital-based study.

    PubMed

    Zaky, Saad; Makhlouf, Nahed A; Abdel Malek, Mohamed O; Bakheet, Ahmed A; Seif, Hany M A; Hamza, Hesham M; Sabry, Abeer M M

    2015-11-01

    To evaluate the short-term outcome of the decision taken by the Hepatoma Board for the treatment of Hepatocellular carcinoma (HCC). This was a prospective descriptive study involving 74 patients with HCC diagnosed by the known criteria. The decisions taken by the Hepatoma Board for the 74 patients were as follows: 1- surgical resection (7 patients), 2- local ablative therapy (LAT) (22 patients), 3- conventional transarterial chemoembolization (TACE) (24 patients), and 4- palliative supportive care (21 patients). The short-term mortality rate was 25.7% of the total patients. The success rate was nearly equal in LAT (68.2%) and surgery (71.4%), whereas the success rate was approximately 33.3% in TACE. There was no difference in the mean total bilirubin level before and after LAT, surgery, or TACE (p>0.05 for each). There was a significant decrease in the mean serum albumin level after TACE (p=0.000). There was a decrease in the mean alpha fetoprotein level after surgery and LAT (p=0.033) for surgery and (p=0.048) for LAT. The management of HCC is better performed through a multidisciplinary team decision. Surgery has comparable outcome to LAT but is more invasive. According to our local experience, conventional TACE has a success rate of 33.3%.

  18. Contribution of laser microdissection-based technology to proteomic analysis in hepatocellular carcinoma developing on cirrhosis

    PubMed Central

    Dos Santos, Alexandre; Thiers, Valérie; Sar, Sokhavuth; Nicolas, Derian; Bensalem, Noura; Yilmaz, Funda; Bralet, Marie-Pierre; Ducot, Béatrice; Bréchot, Christian; Demaugre, France

    2007-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analyzing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and mass spectrometry exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis. PMID:21136705

  19. Prognostic factors of palatal mucoepidermoid carcinoma: a retrospective analysis based on a double-center study

    PubMed Central

    Xu, Wenguang; Wang, Yufeng; Qi, Xiaofeng; Xie, Junqi; Wei, Zheng; Yin, Xiteng; Wang, Zhiyong; Meng, Jian; Han, Wei

    2017-01-01

    Mucoepidermoid carcinoma (MEC) of the palate is a common malignancy of minor salivary glands. This study was designed to identify the prognostic factors for MEC of the palate. The medical records of patients diagnosed with MEC of the palate who visited the Department of Oral and Maxillofacial Surgery at Nanjing Stomatological Hospital and the Department of Stomatology at Central Hospital of Xuzhou were retrospectively studied. The prognostic factors were determined using a Cox proportional hazards model. Furthermore, the expression of cancer stem cell (CSC) markers CD44, CD133, Nanog and Sox2 were detected in neoplastic samples of these patients by immunohistochemistry. As a result, both univariate analysis and multivariate analysis proved a high histological grade and an advanced tumor stage as negative prognostic factors for overall survival. By immunohistochemistry staining and survival analysis, a combination of CD44/CD133/SOX2 was found to have the strongest prognostic value for palatal MEC patients. In conclusion, the proposed nomogram which include histological grade and tumor stage along with cancer stem cell markers provides a more accurate long-term prediction for palatal MEC patients. PMID:28262804

  20. Deregulation of PTEN Expression in Laryngeal Squamous Cell Carcinoma Based on Tissue Microarray Digital Analysis.

    PubMed

    Mastronikolis, Nicholas S; Tsiambas, Evangelos; Papadas, Theodoros A; Karameris, Andreas; Ragos, Vasileios; Peschos, Dimitrios; Mastronikolis, Stylianos N; Papadas, Athanasios T; Liatsos, Christos; Armata, Ilianna E; Fotiades, Panagiotis P

    2017-10-01

    Phosphatase and tensin homolog (PTEN) (gene locus: 10q23.3) -a tumor suppressor gene- is deleted, mutated or epigenetically hyper-methylated in a variety of malignancies. PTEN acts as a negative regulator in PI3K/AKT/mTOR signaling transduction pathway. Our aim was to investigate PTEN protein expression patterns in laryngeal squamous cell carcinomas (LSCC). Using tissue microarray technology, fifty (n=50) primary LSCCs were cored and re-embedded into one recipient block. Immunohistochemistry and digital image analysis were implemented for evaluating protein expression levels. Abnormal protein expression (low to negative staining intensity values) was observed in 28/50 (56%) tissue cores. Overall PTEN expression was associated with the anatomical region of the malignancies (p=0.039), whereas a borderline correlation with the differentiation grade was also assessed (p=0.05). Aberrant expression of PTEN tumor-suppressor gene in LSCCs seems to affect their biological behavior. Well-differentiated tumors express moderate to high protein levels, an evidence of normal gene function, whereas loss of its expression correlates with a progressive tumor dedifferentiation. Additionally, loss of its expression is detected more frequently in specific anatomical regions of the larynx (glottis, predominantly, and partially supraglottis). Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. 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

  2. Prognostic factors of palatal mucoepidermoid carcinoma: a retrospective analysis based on a double-center study.

    PubMed

    Xu, Wenguang; Wang, Yufeng; Qi, Xiaofeng; Xie, Junqi; Wei, Zheng; Yin, Xiteng; Wang, Zhiyong; Meng, Jian; Han, Wei

    2017-03-06

    Mucoepidermoid carcinoma (MEC) of the palate is a common malignancy of minor salivary glands. This study was designed to identify the prognostic factors for MEC of the palate. The medical records of patients diagnosed with MEC of the palate who visited the Department of Oral and Maxillofacial Surgery at Nanjing Stomatological Hospital and the Department of Stomatology at Central Hospital of Xuzhou were retrospectively studied. The prognostic factors were determined using a Cox proportional hazards model. Furthermore, the expression of cancer stem cell (CSC) markers CD44, CD133, Nanog and Sox2 were detected in neoplastic samples of these patients by immunohistochemistry. As a result, both univariate analysis and multivariate analysis proved a high histological grade and an advanced tumor stage as negative prognostic factors for overall survival. By immunohistochemistry staining and survival analysis, a combination of CD44/CD133/SOX2 was found to have the strongest prognostic value for palatal MEC patients. In conclusion, the proposed nomogram which include histological grade and tumor stage along with cancer stem cell markers provides a more accurate long-term prediction for palatal MEC patients.

  3. Mass spectrometry-based salivary proteomics for the discovery of head and neck squamous cell carcinoma.

    PubMed

    Jarai, Tamas; Maasz, Gabor; Burian, Andras; Bona, Agnes; Jambor, Eva; Gerlinger, Imre; Mark, Laszlo

    2012-07-01

    The 5-year survival rates for cases of head and neck squamous cell carcinoma (HNSCC) are only some 60%, mainly because 20%-40% of the patients develop a local relapse in the same or an adjacent anatomic region, even when the surgical margins are histologically tumour-free. Tumours are often discovered in an advanced stage because of the lack of specific symptoms and the diagnostic difficulties. The more advanced the stage of the tumour, the more invasive the diagnostic and treatment interventions needed. An early molecular diagnosis is therefore of vital importance in order to increase the survival rate. The aim of this study was to develop an efficient rapid and sensitive mass spectrometric method for the detection of differentially expressed proteins as tumour-specific biomarkers in saliva from HNSCC patients. Whole saliva samples were collected from patients with HNSCC and from healthy subjects. The proteins were profiled by using SDS PAGE, MALDI TOF/TOF mass spectrometry and the Mascot database search engine. Several potential tumour markers were identified, including annexin A1, beta- and gamma-actin, cytokeratin 4 and 13, zinc finger proteins and P53 pathway proteins. All of these proteins play a proven role in tumour genesis, and have not been detected previously in saliva. Salivary proteomics is a non-invasive specific method for cancer diagnosis and follow-up treatment. It provides facilities for the readily reproducible and reliable detection of tumours in early stages.

  4. Nitrosothiol-Trapping-Based Proteomic Analysis of S-Nitrosylation in Human Lung Carcinoma Cells

    PubMed Central

    Ben-Lulu, Shani; Ziv, Tamar; Weisman-Shomer, Pnina; Benhar, Moran

    2017-01-01

    Nitrosylation of cysteines residues (S-nitrosylation) mediates many of the cellular effects of nitric oxide in normal and diseased cells. Recent research indicates that S-nitrosylation of certain proteins could play a role in tumor progression and responsiveness to therapy. However, the protein targets of S-nitrosylation in cancer cells remain largely unidentified. In this study, we used our recently developed nitrosothiol trapping approach to explore the nitrosoproteome of human A549 lung carcinoma cells treated with S-nitrosocysteine or pro-inflammatory cytokines. Using this approach, we identified about 300 putative nitrosylation targets in S-nitrosocysteine-treated A549 cells and approximately 400 targets in cytokine-stimulated cells. Among the more than 500 proteins identified in the two screens, the majority represent novel targets of S-nitrosylation, as revealed by comparison with publicly available nitrosoproteomic data. By coupling the trapping procedure with differential thiol labeling, we identified nearly 300 potential nitrosylation sites in about 150 proteins. The proteomic results were validated for several proteins by an independent approach. Bioinformatic analysis highlighted important cellular pathways that are targeted by S-nitrosylation, notably, cell cycle and inflammatory signaling. Taken together, our results identify new molecular targets of nitric oxide in lung cancer cells and suggest that S-nitrosylation may regulate signaling pathways that are critically involved in lung cancer progression. PMID:28081246

  5. Treatment of basal cell carcinoma in Scandinavia: evidence or eminence based?

    PubMed

    Helsing, Per; Gjersvik, Petter; Tarstedt, Mikael

    2015-09-01

    Basal cell carcinoma (BCC) is a locally destructive form of skin cancer, mainly affecting Caucasians. There are multiple treatment options for BCC, with excisional surgery being most widely used. Choice of treatment may be dependent on clinical guidelines, local therapeutic traditions, and/or personal experience. Sweden is the only Scandinavian country with treatment guidelines for BCC. Eighty-six dermatologists from Sweden, Denmark, and Norway that were attending a meeting on photodynamic therapy were presented case history and clinical photographs of nine different BCCs and asked to select their treatment of choice among multiple options by the use of an electronic audience response system. Treatment of choice differed substantially between dermatologists from the three countries. Swedish dermatologists more often chose excisional surgery (median 50%, range 0-90%) than their Danish (median 19%, range 0-44%) and Norwegian (median 35%, range 0-65%) colleagues. Very few Swedish dermatologists chose radiation therapy in the four cases where this was an option. Photodynamic therapy was more often selected by Norwegian dermatologists compared to Swedish and Danish dermatologists. The treatment choices of Swedish dermatologists in cases of BCC are generally in line with Swedish treatment guidelines. National treatment guidelines for BCC should be established in all countries, including Denmark and Norway. © 2015 The International Society of Dermatology.

  6. Influence of FDG-PET on Computed Tomography-Based Radiotherapy Planning for Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Zheng Xiaokang Chen Longhua; Wang Quanshi; Wu Hubing; Wang Hongmei; Chen Yongqin; Yan Weipin; Li Qisheng; Xu Yikai

    2007-12-01

    Purpose: Assuming F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) to be more accurate in representing the true disease extent than CT alone, we prospectively designed this study to evaluate how the addition of FDG-PET influences CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma. Patients and Methods: All patients underwent FDG-PET/CT simulation scans. For each patient, the gross tumor volume (GTV) was separately delineated with or without the addition of PET information and defined as GTV{sub PET/CT} and GTV{sub CT}, respectively. Corresponding planning target volumes (PTV) were generated for the GTV{sub CT} (PTV{sub CT}) and GTV{sub PET/CT} (PTV{sub PET/CT}). Three-dimensional conformal radiotherapy plans were separately created for PTV{sub CT} and PTV{sub PET/CT}. To assess the potential geographic miss of the PET/CT-based disease in CT-based treatment planning, the size and location of the GTV{sub PET/CT}, PTV{sub PET/CT}, and PTV{sub CT} were analyzed, and the three-dimensional conformal radiotherapy plans created using the PTV{sub CT} were evaluated with the GTV{sub PET/CT} and PTV{sub PET/CT} information. Results: A total of 43 patients were enrolled in this study. Distant metastasis was found in 4 patients with the addition of the PET information. The 39 patients without distant metastasis proceeded to three-dimensional conformal radiotherapy planning. Inadequate coverage of the GTV{sub PET/CT} and PTV{sub PET/CT} by the PTV{sub CT} occurred in 7 (18%) and 20 (51%) patients, respectively. This resulted in <95% of the GTV{sub PET/CT} and PTV{sub PET/CT} receiving {>=}95% of the prescribed dose in 4 (10%) and 13 (33%) patients, respectively. Conclusions: The addition of FDG-PET information might influence CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma by altering the definition of the target volume, with the potential to avoid a geographic miss of true

  7. Hepatocellular carcinoma.

    PubMed

    Tang, Z Y

    2000-10-01

    Hepatocellular carcinoma (HCC) has ranked second in cancer mortality in China since the 1990s and is increasing in frequency among males in many countries. Hepatitis B and C viruses, aflatoxin and algal toxin in the contaminated drinking water remain major aetiological factors and hepatitis G virus and transfusion-transmitted virus can not be excluded. A prospective randomized control trial screening for HCC in a high-risk population using alpha fetoprotein (AFP) and ultrasonography has demonstrated a decrease in HCC mortality. Rapidly progressing medical imaging has continuously contributed to the improving treatment results. Surgical resection still plays a major role in influencing prognosis of HCC. Studies on recurrence and metastasis after curative resection have become a key issue for further improvement of the surgical outcome. Regional cancer therapies are progressing rapidly, based on the advances in early diagnosis. The advantages and disadvantages of these are noted. Multimodality combination and sequential treatment has been accepted as an important approach for unresectable HCC and cytoreduction and sequential resection have attracted attention. Conformal radiotherapy has shown important potential for HCC treatment. Intra-arterial chemotherapy has been repeatedly proved effective; however, systemic chemotherapy for HCC remains disappointing. The effects of tamoxifen are questionable, whereas alpha-interferon has been shown to have significant potential, particularly in prevention of recurrence. All of these treatments have resulted in continuing improvement of HCC prognosis in some centres.

  8. HPLC-based activity profiling of anti-hepatocellular carcinoma constituents from the Tibetan medicine, Caragana tibetica.

    PubMed

    Song, Ping; Wang, Qiang; Lv, Jing-Nan; Xu, Chan; Lin, Qin-Xiong; Ma, Xin-Hua; Huang, Mi; Yang, Xin-Zhou

    2015-06-01

    During the screening of a traditional Chinese folk herb library against HepG2 and Hep3B cell lines, the EtOAc extract from the Tibetan medicine, Caragana tibetica (CT-EtOAc) exhibited potential anti-hepatocellular carcinoma (anti-HCC) activity. HPLC-based activity profiling was performed for targeted identification of anti-HCC activity from CT-EtOAc by MS-directed purification method. CT-EtOAc was separated by time-based fractionation for further anti-HCC bioassay by a semipreparative HPLC column (150 mm × 10 mm i.d., 5 μm) with a single injection of 5 mg. Bioassay-guided and ESIMS-directed large scale purification was performed with a single injection of 400 mg of CT-EtOAc by peak-based fractionation. A 1.4-mm heavy wall micro NMR tube with z-gradient was used to measure one and two dimensional NMR spectra for the minor or trace amounts of components of the extract. Two active compounds could be elucidated as naringenin chalcone (CT-1) and 3-hydroxy-8, 9-dimethoxypterocarpan (CT-2) relevant to anti-HCC effects for the EtOAc extract of C. tibetica rapidly and unambiguously by this protocol.

  9. Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

    PubMed Central

    Kuo, Ming-Jeng; Chen, Hsiu-Hsi; Chen, Chi-Ling; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Lin, Yu-Min; Liao, Chao-Sheng; Chang, Hung-Chuen; Lin, Yueh-Shih; Yen, Amy Ming-Fang

    2016-01-01

    AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval. PMID:27022228

  10. Near-infrared quantum-dot-based non-invasive in vivo imaging of squamous cell carcinoma U14

    NASA Astrophysics Data System (ADS)

    Cao, Yu'an; Yang, Kai; Li, Zhigang; Zhao, Cheng; Shi, Chunmeng; Yang, Jia

    2010-11-01

    Near-infrared (near-ir) quantum dots (QDs) are well known for their excellent optical characteristics. They hold great potential for applications in non-invasive long term observation and tracing of cells in vivo. Here, near-ir QDs with an emission wavelength of 800 nm (QD800) were used to label squamous cell carcinoma cell line U14 (U14/QD800). The effect of tissue depth and animal fur on the imaging sensitivity and stability was evaluated following subcutaneous and intramuscular injection into Kunming mice, employing an in vivo imaging system. We have demonstrated that QD800-based visual in vivo imaging increased the sensitivity of cancer early detection by a factor of 100 compared with traditional detection methods. More importantly, this study proved for the first time that animal fur has a serious impact on the detection sensitivity and duration of QD-based in vivo imaging. In general, the duration and sensitivity of QD800 for in vivo imaging were not greatly affected by a depth less than 1.8 ± 0.21 mm (subcutaneous or intramuscular). This study provides critical reference data for further research on near-ir QD-based early detection and in vivo visual observation of cancer.

  11. Robust demarcation of basal cell carcinoma by dependent component analysis-based segmentation of multi-spectral fluorescence images.

    PubMed

    Kopriva, Ivica; Persin, Antun; Puizina-Ivić, Neira; Mirić, Lina

    2010-07-02

    This study was designed to demonstrate robust performance of the novel dependent component analysis (DCA)-based approach to demarcation of the basal cell carcinoma (BCC) through unsupervised decomposition of the red-green-blue (RGB) fluorescent image of the BCC. Robustness to intensity fluctuation is due to the scale invariance property of DCA algorithms, which exploit spectral and spatial diversities between the BCC and the surrounding tissue. Used filtering-based DCA approach represents an extension of the independent component analysis (ICA) and is necessary in order to account for statistical dependence that is induced by spectral similarity between the BCC and surrounding tissue. This generates weak edges what represents a challenge for other segmentation methods as well. By comparative performance analysis with state-of-the-art image segmentation methods such as active contours (level set), K-means clustering, non-negative matrix factorization, ICA and ratio imaging we experimentally demonstrate good performance of DCA-based BCC demarcation in two demanding scenarios where intensity of the fluorescent image has been varied almost two orders of magnitude.

  12. 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

  13. 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

  14. 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

  15. 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

    Waliszewski, Przemyslaw

    2016-01-01

    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. The global fractal capacity D 0, information D 1 and correlation D 2 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. Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D 0-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 D 1 failed to define the same classes of equivalence. The pairs (D 0, LFD), (D 0, H), (D 0, λ), (D 1, LFD), (D 1, H), (D 1, 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 D 0 < 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 D 0 > 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. The cut-off D 0-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 relevant information. Two novel

  16. 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

  17. Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma.

    PubMed

    Wang, Y; Jiang, T; Li, Z; Lu, L; Zhang, R; Zhang, D; Wang, X; Tan, J

    2017-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide. Although great progress in diagnosis and management of HCC have been made, the exact molecular mechanisms remain poorly understood. The study aims to identify potential biomarkers for HCC progression, mainly at transcription level. In this study, chip data GSE 29721 was utilized, which contains 10 HCC samples and 10 normal adjacent tissue samples. Differentially expressed genes (DEGs) between two sample types were selected by t-test method. Following, the differentially co-expressed genes (DCGs) and differentially co-expressed Links (DCLs) were identified by DCGL package in R with the threshold of q < 0.25. Afterwards, pathway enrichment analysis of the DCGs was carried out by DAVID. Then, DCLs were mapped to TRANSFAC database to reveal associations between relevant transcriptional factors (TFs) and their target genes. Quantitative real-time RT-PCR was performed for TFs or genes of interest. As a result, a total of 388 DCGs and 35,771 DCLs were obtained. The predominant pathways enriched by these genes were Cytokine-cytokine receptor interaction, ECM-receptor interaction and TGF-β signaling pathway. Three TF-target interactions, LEF1-NCAM1, EGR1-FN1 and FOS-MT2A were predicted. Compared with control, expressions of the TF genes EGR1, FOS and ETS2 were all up-regulated in the HCC cell line, HepG2; while LEF1 was down-regulated. Except NCAM1, all the target genes were up-regulated in HepG2. Our findings suggest these TFs and genes might play important roles in the pathogenesis of HCC and may be used as therapeutic targets for HCC management.

  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. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database

    PubMed Central

    Lin, Pei-Yang; Zhang, Jie; Song, Chuan-Gui; Shao, Zhi-Ming

    2017-01-01

    Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients. PMID:28008158

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

    PubMed

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

    2015-03-12

    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.

  1. Prediction and diagnosis of renal cell carcinoma using nuclear magnetic resonance-based serum metabolomics and self-organizing maps

    PubMed Central

    Zheng, Hong; Ji, Jiansong; Zhao, Liangcai; Chen, Minjiang; Shi, An; Pan, Linlin; Huang, Yiran; Zhang, Huajie; Dong, Baijun; Gao, Hongchang

    2016-01-01

    Diagnosis of renal cell carcinoma (RCC) at an early stage is challenging, but it provides the best chance for cure. We aimed to develop a predictive diagnostic method for early-stage RCC based on a biomarker cluster using nuclear magnetic resonance (NMR)-based serum metabolomics and self-organizing maps (SOMs). We trained and validated the SOM model using serum metabolome data from 104 participants, including healthy individuals and early-stage RCC patients. To assess the predictive capability of the model, we analyzed an independent cohort of 22 subjects. We then used our method to evaluate changes in the metabolic patterns of 23 RCC patients before and after nephrectomy. A biomarker cluster of 7 metabolites (alanine, creatine, choline, isoleucine, lactate, leucine, and valine) was identified for the early diagnosis of RCC. The trained SOM model using a biomarker cluster was able to classify 22 test subjects into the appropriate categories. Following nephrectomy, all RCC patients were classified as healthy, which was indicative of metabolic recovery. But using a diagnostic criterion of 0.80, only 3 of the 23 subjects could not be confidently assessed as metabolically recovered after nephrectomy. We successfully followed-up 17 RCC patients for 8 years post-nephrectomy. Eleven of these patients who diagnosed as metabolic recovery remained healthy after 8 years. Our data suggest that a SOM model using a biomarker cluster from serum metabolome can accurately predict early RCC diagnosis and can be used to evaluate postoperative metabolic recovery. PMID:27463020

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

    PubMed

    Wang, Hui; Chen, Jiao; Feng, Yun; Zhou, Wenjie; Zhang, Jihua; Yu, Y U; Wang, Xiaoqian; Zhang, Ping

    2015-06-01

    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, (1)H 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, (1)H NMR-based metabolomic analysis has a high potential for monitoring the formation of MDR during clinical tumor chemotherapy in the future.

  3. Prediction and diagnosis of renal cell carcinoma using nuclear magnetic resonance-based serum metabolomics and self-organizing maps.

    PubMed

    Zheng, Hong; Ji, Jiansong; Zhao, Liangcai; Chen, Minjiang; Shi, An; Pan, Linlin; Huang, Yiran; Zhang, Huajie; Dong, Baijun; Gao, Hongchang

    2016-09-13

    Diagnosis of renal cell carcinoma (RCC) at an early stage is challenging, but it provides the best chance for cure. We aimed to develop a predictive diagnostic method for early-stage RCC based on a biomarker cluster using nuclear magnetic resonance (NMR)-based serum metabolomics and self-organizing maps (SOMs). We trained and validated the SOM model using serum metabolome data from 104 participants, including healthy individuals and early-stage RCC patients. To assess the predictive capability of the model, we analyzed an independent cohort of 22 subjects. We then used our method to evaluate changes in the metabolic patterns of 23 RCC patients before and after nephrectomy. A biomarker cluster of 7 metabolites (alanine, creatine, choline, isoleucine, lactate, leucine, and valine) was identified for the early diagnosis of RCC. The trained SOM model using a biomarker cluster was able to classify 22 test subjects into the appropriate categories. Following nephrectomy, all RCC patients were classified as healthy, which was indicative of metabolic recovery. But using a diagnostic criterion of 0.80, only 3 of the 23 subjects could not be confidently assessed as metabolically recovered after nephrectomy. We successfully followed-up 17 RCC patients for 8 years post-nephrectomy. Eleven of these patients who diagnosed as metabolic recovery remained healthy after 8 years. Our data suggest that a SOM model using a biomarker cluster from serum metabolome can accurately predict early RCC diagnosis and can be used to evaluate postoperative metabolic recovery.

  4. Phase I dose-escalation study of helical intensity-modulated radiotherapy-based stereotactic body radiotherapy for hepatocellular carcinoma

    PubMed Central

    Kim, Jun Won; Seong, Jinsil; Lee, Ik Jae; Woo, Joong Yeol; Han, Kwang-Hyub

    2016-01-01

    Background Phase I trial was conducted to determine feasibility and toxicity of helical intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). Results Eighteen patients (22 lesions) were enrolled. With no DLT at 52 Gy (13 Gy/fraction), protocol was amended for further escalation to 60 Gy (15 Gy/fraction). Radiologic complete response rate was 88.9%. Two outfield intrahepatic, 2 distant, 4 concurrent local and outfield, and 1 concurrent local, outfield and distant failures (no local failure at dose levels 3–4) occurred. The worst toxicity was grade 3 hematologic in five patients, with no gastrointestinal toxicity > grade 1. At median follow-up of 28 months for living patients, 2-year local control, progression-free (PFS), and overall survival rates were 71.3%, 49.4% and 69.3%, respectively. Multi-segmental recurrences prior to SBRT was independent prognostic factor for PFS (p = 0.033). Materials and Methods Eligible patients had Child-Pugh's class A or B, unresectable HCC, ≤ 3 lesions, and cumulative tumor diameter ≤ 6 cm. Starting at 36 Gy in four fractions, dose was escalated with 2 Gy/fraction per dose-level. CTCAE v 3.0 ≥ grade 3 gastrointestinal toxicity and radiation induced liver disease defined dose-limiting toxicity (DLT). Conclusions Helical IMRT-based SBRT was tolerable and showed encouraging results. Confirmatory phase II trial is underway. PMID:27213593

  5. A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

    PubMed Central

    Li, Zhigang; Perry, Ann E.; Spencer, Steven K.; Gandolfi, A. Jay; Karagas, Margaret R.

    2013-01-01

    Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association. Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178 PMID:23872349

  6. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    SciTech Connect

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira

    2010-04-15

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term {alpha} and the dose per fraction. The estimated values of {alpha} and OER from data fitting were 0.396 Gy{sup -1} and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  7. Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

    PubMed

    Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

    2016-10-20

    The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

  8. 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.

  9. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    PubMed

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2017-06-01

    Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis

    PubMed Central

    Chen, Ming-Yang; Wang, Yu-Chao; Wu, Tsung-Han; Lee, Chen-Fang; Wu, Ting-Jung; Chou, Hong-Shiue; Tsang, Ngan-Ming; Lee, Wei-Chen

    2016-01-01

    Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management. PMID:27999803

  15. A new surgical strategy for treatment of tongue squamous cell carcinoma based on anatomic study with preliminary clinical evaluation.

    PubMed

    Ren, Zhen-Hu; Wu, Han-Jiang; Zhang, Sheng; Wang, Kai; Gong, Zhao-Jian; He, Zhi-Jing; Peng, Jie

    2015-10-01

    This study characterized the infiltration of primary tumors along the intrinsic and extrinsic muscles of the tongue in oral tongue squamous cell carcinoma (OTSCC), to create a new surgical strategy that is suitable for most stages. A preliminary evaluation of this novel surgical approach was also conducted. An anatomic study of macroscopic specimens from 10 human cadavers and 100 OTSCC patients was conducted. The anatomic characteristics of the primary tumors and the origin and distribution of fibers of the intrinsic and extrinsic tongue muscles were observed and measured. After initial treatment with curative intent, the 100 patients were regularly followed-up with clinical examination and imaging. Based on the anatomic characteristics of the primary tumors and tongue muscles, a new surgical approach was developed, and was described as muscle anatomy tongue surgery (MATS). MATS proved suitable for almost all stages of OTSCC. According to the morphology of the invasive tumor front, the 100 cases were divided into four types. The rate of 2-year local disease control was 98%, locoregional control 86%, disease-free survival 85%, and overall survival 89%. Tongue functions were perfectly recovered in more than 60% of the patients. Application of the principles of MATS to the treatment of OTSCC proved suitable for almost all stages of the disease. MATS is a novel surgical technique that may improve outcomes in tongue cancer surgery. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy.

    PubMed

    Huang, Can; Li, Na-Mei; Gao, Pei; Yang, Sa; Ning, Qian; Huang, Wen; Li, Zhi-Ping; Ye, Peng-Ju; Xiang, Li; He, Dong-Xiu; Tan, Xiang-Wen; Yu, Cui-Yun

    2017-11-01

    A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.

  17. Comparison of Histological and Proliferation Features of Canine Oral Squamous Cell Carcinoma Based on Intraoral Location: 36 Cases.

    PubMed

    Mestrinho, Lisa A; Pissarra, Hugo; Carvalho, Sandra; Peleteiro, Maria C; Gawor, Jerzy; Niza, Maria M R E

    2017-06-01

    Grade and labeling indices for immunohistochemical tumor proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) were evaluated in 36 cases of canine oral squamous cell carcinoma (OSCC) based upon intraoral location. Grade was significantly associated with location ( P = .035). Grade II tumors were most frequently diagnosed. Grade I tumors were identified in the gingiva and the buccal mucosa, and grade III tumors were seen in the gingiva and the tonsillar region. Animals with tumors arising from the tonsils and of the tongue tended to be older ( P = .007), and those in the former group were more likely to have metastatic disease at the time of diagnosis ( P = .001). Mean expression of PCNA and Ki-67 proliferation index (PI) for all tumors were 62.54% and 50.70%, respectively, and there was a statistical significant association between the 2 variables ( R = .70; P < .001). Proliferation index was not associated with any of the intraoral locations evaluated, but higher PCNA PI was significantly associated with grade ( P = .031). Ki-67 PI was significantly associated with lymph node metastasis at the time of diagnosis, especially for OSCC of gingival location ( P = .028). The results obtained in this study are preliminary but clinically relevant, since they provide information that can explain differences in biologic behavior among intraoral locations and contribute to more accurate tumor staging to support the choice for different treatment strategies available for OSCC.

  18. Cytoreductive partial nephrectomy does not undermine cancer control in metastatic renal cell carcinoma: a population-based study.

    PubMed

    Capitanio, Umberto; Zini, Laurent; Perrotte, Paul; Shariat, Shahrokh F; Jeldres, Claudio; Arjane, Philippe; Pharand, Daniel; Widmer, Hugues; Péloquin, François; Montorsi, Francesco; Patard, Jean-Jacques; Karakiewicz, Pierre I

    2008-11-01

    We examined the population-based rates of cancer-specific survival in patients with metastatic renal cell carcinoma (MRCC) treated with either partial (PN) or radical cytoreductive nephrectomy (RN). Patients diagnosed with MRCC and treated with either PN or RN were identified within nine SEER cancer registries. Matched and unmatched Kaplan-Meier survival analyses, as well as multivariable Cox regression models compared the effect of RN (n = 1997, 97.8%) vs. PN (n = 46, 2.2%) on cancer-specific survival (CSS). Covariates consisted of age, gender, community type (rural vs urban), race, Surveillance, Epidemiology, and End Results (SEER) registry, tumor size and year of diagnosis. In multivariable unmatched Cox regression analyses, no statistically significantly difference was found in CSS between the two groups (hazard ratio [HR] 1.40, P = .16). Similarly, no difference in CSS was found in the matched analyses (HR 1.35, log rank P = .34). Cytoreductive PN does not appear to undermine survival in patients with MRCC.

  19. Weighted risk score-based multifactor dimensionality reduction to detect gene-gene interactions in nasopharyngeal carcinoma.

    PubMed

    Li, Chao-Feng; Luo, Fu-Tian; Zeng, Yi-Xin; Jia, Wei-Hua

    2014-06-13

    Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.

  20. 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

  1. 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.

  2. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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

    2015-02-06

    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.

  4. 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

  5. Adrenocortical carcinoma in children: first population-based clinicopathological study with long-term follow-up.

    PubMed

    Kerkhofs, T M A; Ettaieb, M H T; Verhoeven, R H A; Kaspers, G J L; Tissing, W J E; Loeffen, J; Van den Heuvel-Eibrink, M M; De Krijger, R R; Haak, H R

    2014-12-01

    Adrenocortical carcinoma (ACC) is rare in both adult and pediatric populations. Literature suggests significant differences between children and adults in presentation, histological properties and outcome. The aim of this first nationwide study on pediatric ACC was to describe the incidence, presentation, pathological characteristics, treatment and survival in The Netherlands. All ACC patients aged <20 years at diagnosis and registered in the population-based Netherlands Cancer Registry between 1993 and 2010 were included. Clinical data were extracted from medical records. Archival histological slides were collected via the Dutch Pathology Registry (PALGA). We compared our findings to all clinical studies on pediatric ACC that were found on PubMed. Based on the results, 12 patients were identified: 8 females and 4 males. The median age was 4.1 years (range 1.1-18.6). The population-based age-standardized incidence rate for patients <20 years was 0.18 per million person-years. Autonomous hormonal secretion was present in 10 patients. Seven patients were aged ≤4 years at diagnosis, 5 presented with localized disease and 2 with locally advanced disease. Five patients were aged ≥5 years, 3 presented with distant metastases and 1 with locally advanced disease. For all patients, histological examination displayed malignant characteristics. All patients aged ≤4 years at diagnosis survived; the median follow-up was 97 months (57-179 months). All patients aged ≥5 years died; the median survival was 6 months (0-38 months). Pediatric ACC is extremely rare in the Western world. The clinical outcome was remarkably better in patients aged ≤4 years. This is in accordance with less advanced stage of disease at presentation, yet contrasts with the presence of adverse histological characteristics. Clinical management in advanced disease is adapted from adult practice in the absence of evidence regarding pediatric ACC.

  6. 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.

  7. 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

  8. Hepatocellular Carcinoma Surveillance Among Patients With Cirrhosis in a Population-based Integrated Health Care Delivery System.

    PubMed

    Singal, Amit G; Tiro, Jasmin; Li, Xilong; Adams-Huet, Beverley; Chubak, Jessica

    2017-08-01

    Fewer than 1 in 5 patients with cirrhosis receive hepatocellular carcinoma (HCC) surveillance; however, most studies were performed in select patient populations, which may not be informative of practice patterns in population-based community practices. Further, few reported guideline-concordant consistent surveillance rates. Characterize guideline-concordant HCC surveillance rates and patient-level factors associated with surveillance among a population-based cohort of patients with cirrhosis. We retrospectively characterized HCC surveillance among cirrhosis patients followed between January 2010 and December 2012 at an integrated health care delivery system in Washington state. Consistent surveillance was defined as an ultrasound every 6 months, and inconsistent surveillance was defined as ≥1 ultrasound during the 2-year follow-up period. Univariate and multivariate analyses were conducted to identify correlates of HCC surveillance receipt. Of 1137 patients with cirrhosis, 22 (2%) underwent consistent surveillance, 371 (33%) had inconsistent surveillance, and 744 (65%) received no surveillance during follow-up. Correlates of HCC surveillance receipt in multivariate analysis included Gastroenterology/Hepatology subspecialty care [odds ratio (OR), 1.88; 95% confidence interval (CI), 1.44-2.46], Child Pugh B/C cirrhosis (OR, 1.61; 95% CI, 1.07-2.43), elevated aspartate aminotransferase (OR, 1.63; 95% CI, 1.13-2.35), and etiology of liver disease. Compared with hepatitis C-infected patients, patients with hepatitis B infection were more likely to undergo surveillance (OR, 2.72; 95% CI, 1.28-5.81), whereas patients with alcohol-related cirrhosis (OR, 0.63; 95% CI, 0.42-0.93) and nonalcoholic steatohepatitis (OR, 0.39; 95% CI, 0.28-0.56) were less likely to undergo surveillance. Although one third of patients undergo inconsistent HCC surveillance, <2% of patients receive guideline-concordant biannual HCC surveillance.

  9. Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization

    PubMed Central

    Prajapati, Hasmukh J.

    2017-01-01

    Purpose To develop the treatment algorithm from multivariate survival analyses (MVA) in patients with Barcelona clinic liver cancer (BCLC) C (advanced) Hepatocellular carcinoma (HCC) patients treated with Trans-arterial Chemoembolization (TACE). Methods Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs) was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP) staging system (SS). Results Overall median survival (OS) was 16.2 months. In HCC patients with venous thrombosis (VT) of large vein [main portal vein (PV), right or left PV, hepatic vein, inferior vena cava] (22.7%) versus small vein (segmental/subsegmental PV) (9.7%) versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001). On MVA, the significant independent prognostic factors (PFs) of survival were CP class, eastern cooperative oncology group (ECOG) performance status (PS), single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001). The treatment plan was proposed according to the different stages. Conclusion On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs) of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments. PMID:28170405

  10. 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.

  11. Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base.

    PubMed

    Wong, Andrew T; Shao, Meng; Rineer, Justin; Osborn, Virginia; Schwartz, David; Schreiber, David

    2016-11-09

    Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease.

  12. Final Results Following Platin-based Exclusive Chemotherapy for Selected Patients with Squamous Cell Carcinoma of the Larynx and Pharynx

    PubMed Central

    Holsinger, F. Christopher; Lin, Heather Y.; Bassot, Vincent; Laccourreye, Ollivier

    2009-01-01

    Purpose To determine the long-term outcomes for patients with squamous cell carcinoma of the larynx and pharynx treated with platin-based exclusive chemotherapy (EC) after complete clinical response (CCR) to induction chemotherapy. Materials and Methods 142 patients who achieved a CCR after platin-based induction chemotherapy were treated exclusively with additional chemotherapy. 98.6% were followed for a minimum of 3 years or until death; 35 patients had >10yrs of follow-up. Results Survival at 1- and 5-year was 95.8% and 61.2%, respectively. The main causes of death were metachronous second primaries (27) and intercurrent disease (21). Death related to EC was not encountered and only two patients (1.4%) had grade 4 toxicity. In multivariate analysis, primary tumor arising outside the glottic larynx (p=.0001), and Charlson comorbidity index>1 (p=.0001) were associated with a statistically significant reduction in survival. The 1-and 5-year Kaplan-Meier local control estimates were 76.1% and 50.7%, respectively. Salvage treatment resulted in an observed final 93.0% local control rate and varied from 97.2% in patients with glottic cancer to 88.7% in patients with tumor originating from other sites (p = .097). PF chemotherapy allowed for successful modulation of local therapy in 54.9% of patients. Conclusions For selected patients, EC may provide long-term durable disease control. For patients with relapse after EC, this approach does not diminish survival and maintains function in a majority of patients. Future work should be directed to select markers of response to PF chemotherapy and thereby to identify which patients are optimally suited for this approach. PMID:19551883

  13. Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study.

    PubMed

    Jiang, Ke; Lei, Jianyong; Li, Canjun; Shu, Kunpeng; Li, Wenbin; Zhang, Yuwei; Li, Zhihui; Gong, Rixiang; Zhu, Jingqiang

    2017-09-01

    The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores. Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores. Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence. PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability. © 2017 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  15. Stereotactic body radiation therapy in hepatocellular carcinoma: Optimal treatment strategies based on liver segmentation and functional hepatic reserve

    PubMed Central

    Wang, Po-Ming; Chung, Na-Na; Hsu, Wei-Chung; Chang, Feng-Ling; Jang, Chin-Jyh; Scorsetti, Marta

    2015-01-01

    Aim To discuss current dosage for stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) patients and suggest alternative treatment strategies according to liver segmentation as defined by the Couinaud classification. Background SBRT is a safe and effective alternative treatment for HCC patients who are unable to undergo liver ablation/resection. However, the SBRT fractionation schemes and treatment planning strategies are not well established. Materials and methods In this article, the latest developments and key findings from research studies exploring the efficacy of SBRT fractionation schemes for treatment of HCC are reviewed. Patients’ characteristics, fractionation schemes, treatment outcomes and toxicities were compiled. Special attention was focused on SBRT fractionation approaches that take into consideration liver segmentation according to the Couinaud classification and functional hepatic reserve based on Child–Pugh (CP) liver cirrhosis classification. Results The most common SBRT fractionation schemes for HCC were 3 × 10–20 Gy, 4–6 × 8–10 Gy, and 10 × 5–5.5 Gy. Based on previous SBRT studies, and in consideration of tumor size and CP classification, we proposed 3 × 15–25 Gy for patients with tumor size <3 cm and adequate liver reserve (CP-A score 5), 5 × 10–12 Gy for patients with tumor sizes between 3 and 5 cm or inadequate liver reserve (CP-A score 6), and 10 × 5–5.5 Gy for patients with tumor size >5 cm or CP-B score. Conclusions Treatment schemes in SBRT for HCC vary according to liver segmentation and functional hepatic reserve. Further prospective studies may be necessary to identify the optimal dose of SBRT for HCC. PMID:26696781

  16. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study.

    PubMed

    Zhang, Lu-Ning; Gao, Yuan-Hong; Lan, Xiao-Wen; Tang, Jie; OuYang, Pu-Yun; Xie, Fang-Yun

    2015-10-01

    The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study. Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis. After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis. In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database

    PubMed Central

    2014-01-01

    Background Neuroendocrine carcinoma (NEC) of the breast is a rare type of carcinoma that has not been well studied or characterized. Of the limited number of studies reported in the literature, most are case reports. A few small retrospective series studies have been reported. Methods We reviewed data on 142 cases of mammary NEC recorded in the surveillance, epidemiology, and end results (SEER) database during 2003–2009 and evaluated disease incidence and patient age, sex, and race/ethnicity; clinicopathologic characteristics; and survival in comparison to invasive mammary carcinoma, not otherwise specified. We also performed univariate and multivariate analyses to identify prognostic factors in this disease. Results Review of the 142 SEER cases revealed that NEC is an aggressive variant of invasive mammary carcinoma. It generally occurred in older women (>60 years); present with larger tumor size (>20 mm), higher histologic grade, and higher clinical stage; and result in shorter overall survival and disease-specific survival than invasive mammary carcinoma, not otherwise specified (IMC-NOS). Overall survival and disease-specific survival were shorter in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was an adverse prognostic factor independent of other known prognostic factors, including age, tumor size, nodal status, histologic grade, estrogen/progesterone receptor status, and therapy. Conclusions NEC is a rare but aggressive type of mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely clinical entity. PMID:24589259

  18. Circulating tumor cell detection in hepatocellular carcinoma based on karyoplasmic ratios using imaging flow cytometry

    PubMed Central

    Liu, Zixin; Guo, Weixing; Zhang, Dandan; Pang, Yanan; Shi, Jie; Wan, Siqin; Cheng, Kai; Wang, Jiaqi; Cheng, Shuqun

    2016-01-01

    Circulating tumor cells (CTCs) originate from tumor tissues and are associated with cancer prognosis. However, existing technologies for CTC detection are limited owing to a lack of specific or accurate biomarkers. Here, we developed a new method for CTC detection based on the karyoplasmic ratio, without biomarkers. Consecutive patients with liver cancer or non-cancer liver diseases were recruited. CTCs in blood samples were analyzed by imaging flow cytometry based on the karyoplasmic ratio as well as EpCAM and CD45. Microvascular invasion (MVI), tumor recurrence, and survival were recorded for all patients. A total of 56.2 ± 23.8/100,000 cells with high karyoplasmic ratios (HKR cells) were detected in cancer patients, which was higher than the number of HKR cells in the non-cancer group (7.6 ± 2.2/100,000). There was also a difference in HKR cells between liver cancer patients with and without MVI. Based on a receiver operating characteristic curve analysis, the threshold was 21.8 HKR cells per 100,000 peripheral blood mononuclear cells, and the area under the curve was higher than those of traditional methods (e.g., CD45 and EpCAM staining). These results indicate that the new CTC detection method was more sensitive and reliable than existing methods. Accordingly, it may improve clinical CTC detection. PMID:28009002

  19. 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.

  20. 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.

  1. Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based cohort study in Japan.

    PubMed

    Ishiguro, Seiji; Inoue, Manami; Tanaka, Yasuhito; Mizokami, Masashi; Iwasaki, Motoki; Tsugane, Shoichiro

    2009-02-01

    Aminotransferase level is presumed to be a marker of hepatic inflammation, but uncertainty remains whether elevated aminotransferase levels are associated with an increased risk of hepatocellular carcinoma (HCC). We evaluated the incidence of HCC by aminotransferase level in 19 812 middle-aged and older individuals with and without hepatitis virus infection from a large-scale population-based cohort study (JPHC Study cohort II) in Japan. Hepatitis virus infection was identified at baseline in 1236 participants, namely 737 (3.7%) with hepatitis C virus, 479 (2.4%) with hepatitis B virus, and 20 (0.1%) with both. By the end of follow-up, a total of 109 newly arising HCC cases were diagnosed (71 men, 38 women), of which 87 (79.8%) had evidence of viral etiology. Alanine aminotransferase (ALT) was concentration-dependently associated with an increased risk of HCC in both virus-positive and virus-negative participants. Compared with virus-negative participants with ALT levels of less than 30 IU/l, a significant increase in the risk of HCC was observed in virus-negative participants with an ALT level greater than 30 IU/l, and in virus-positive participants with an ALT less than 30 IU/l, 30-69 IU/l, and > or =70 IU/l [Hazard ratio (95% confidence interval): 9.4 (3.9-22.3), 15.2 (6.1-37.6), 180.5 (89.4-364.2), 454.2 (221.5-931.2), respectively; P for trend <0.001]. In conclusion, our findings suggest that elevated ALT levels are strongly associated with the incidence of HCC regardless of hepatitis virus positivity. This finding indicates that ALT level is a good independent determinant of the need for intervention. Clinical application of these findings may help decrease HCC-associated mortality in hepatitis virus-endemic regions.

  2. A Clinical Trial Using Attrition Combined with 5-Aminolevulinic Acids Based Photodynamic Therapy in Treating Squamous Cell Carcinoma

    PubMed Central

    Peng, Jianzhong; Feng, Weiguo; Luo, Xianyan; Wang, Tao; Xiang, Wenzhong; Dai, Yeqin; Zhu, Jingyu; Zheng, Junhui

    2017-01-01

    Background Squamous cell carcinoma (SCC) is the second most common type of skin cancer, for which non- or mini-invasive treatment is of critical importance. 5-aminolevulinic acids based photodynamic therapy (ALA-PDT) is a mini-invasive approach that causes focal tumor cell injury, apoptosis, and necrosis through light sensitivity. The efficacy of combining ALA-PDT and surgery in treating SCC, however, has not been demonstrated. Material/Methods A total of 60 SCC patients were randomly assigned into attrition plus ALA-PDT group (experimental group) and single ALA-PDT treatment group (control group). Clinical efficacy, recurrence rate, and adverse effects were analyzed in conjunction with H&E staining and immunohistochemistry (IHC) staining for p53 expression. Results The overall effective rate of the experimental group was 73.3%, which was significantly higher than that of the control group (46.7%). The experimental group also had a lower recurrence rate (16.6% versus 30.0%, p<0.05). Similar rates of adverse effects existed between the two groups. After treatment, abnormal cells disappeared, while the p53 positive rate after treatment was elevated in the two groups (p<0.05 comparison of before and after treatment). The experimental group had a higher p53 positive rate compared to the control group (p<0.05). Conclusions Combined therapy of attrition with ALA-PDT significantly elevated the effective treatment rate and can decrease the recurrence rate with reliable safety in treating SCC, thus ALA-PDT can be used as an optimal plan for SCC treatment. PMID:28314866

  3. Identifying the optimal gene and gene set in hepatocellular carcinoma based on differential expression and differential co-expression algorithm.

    PubMed

    Dong, Li-Yang; Zhou, Wei-Zhong; Ni, Jun-Wei; Xiang, Wei; Hu, Wen-Hao; Yu, Chang; Li, Hai-Yan

    2017-02-01

    The objective of this study was to identify the optimal gene and gene set for hepatocellular carcinoma (HCC) utilizing differential expression and differential co-expression (DEDC) algorithm. The DEDC algorithm consisted of four parts: calculating differential expression (DE) by absolute t-value in t-statistics; computing differential co-expression (DC) based on Z-test; determining optimal thresholds on the basis of Chi-squared (χ2) maximization and the corresponding gene was the optimal gene; and evaluating functional relevance of genes categorized into different partitions to determine the optimal gene set with highest mean minimum functional information (FI) gain (Δ*G). The optimal thresholds divided genes into four partitions, high DE and high DC (HDE-HDC), high DE and low DC (HDE-LDC), low DE and high DC (LDE‑HDC), and low DE and low DC (LDE-LDC). In addition, the optimal gene was validated by conducting reverse transcription-polymerase chain reaction (RT-PCR) assay. The optimal threshold for DC and DE were 1.032 and 1.911, respectively. Using the optimal gene, the genes were divided into four partitions including: HDE-HDC (2,053 genes), HED-LDC (2,822 genes), LDE-HDC (2,622 genes), and LDE-LDC (6,169 genes). The optimal gene was microtubule‑associated protein RP/EB family member 1 (MAPRE1), and RT-PCR assay validated the significant difference between the HCC and normal state. The optimal gene set was nucleoside metabolic process (GO\\GO:0009116) with Δ*G = 18.681 and 24 HDE-HDC partitions in total. In conclusion, we successfully investigated the optimal gene, MAPRE1, and gene set, nucleoside metabolic process, which may be potential biomarkers for targeted therapy and provide significant insight for revealing the pathological mechanism underlying HCC.

  4. 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

  5. Revalidation of a prognostic score model based on complete blood count for nasopharyngeal carcinoma through a prospective study

    PubMed Central

    Li, Xiaohui; Chang, Hui; Tao, Yalan; Wang, Xiaohui; Gao, Jin; Zhang, Wenwen; Chen, Chen; Xia, Yunfei

    2016-01-01

    Objective In our previous work, we incorporated complete blood count (CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal carcinoma (NPC). The purpose of this study was to revalidate the accuracy of the model, and its superiority to TNM stage, through data from a prospective study. Methods CBC of 249 eligible patients from the 863 Program No. 2006AA02Z4B4 was evaluated. Prognostic index (PI) of each patient was calculated according to the score model. Then they were divided by the PI into three categories: the low-, intermediate-and high-risk patients. The 5-year disease-specific survival (DSS) of the three categories was compared by a log-rank test. The model and TNM stage (7th edition) were compared on efficiency for predicting the 5-year DSS, through comparison of the area under curve (AUC) of their receiver-operating characteristic curves. Results The 5-year DSS of the low-, intermediate-and high-risk patients were 96.0%, 79.1% and 62.2%, respectively. The low-and intermediate-risk patients had better DSS than the high-risk patients (P<0.001 and P<0.005, respectively). And there was a trend of better DSS in the low-risk patients, compared with the intermediate-risk patients (P=0.049). The AUC of the model was larger than that of TNM stage (0.726 vs. 0.661, P=0.023). Conclusions A CBC-based prognostic score model was revalidated to be accurate and superior to TNM stage on predicting 5-year DSS of NPC. PMID:27877005

  6. Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data.

    PubMed

    Yu, Rentao; Tan, Zhaoxia; Xiang, Xiaomei; Dan, Yunjie; Deng, Guohong

    2017-09-01

    Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied. A total of 14,861 samples were tested in Southwest Hospital in over 2 years' time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively. A total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0-33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0-348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time. Our data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.

  7. Low-dose Methotrexate Enhances Aminolevulinate-based Photodynamic Therapy in Skin Carcinoma Cells In-vitro and In-vivo

    PubMed Central

    Anand, Sanjay; Honari, Golara; Hasan, Tayyaba; Elson, Paul; Maytin, Edward V.

    2009-01-01

    Purpose To improve treatment efficacy and tumor cell selectivity of δ-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), via pretreatment of cells and tumors with methotrexate (MTX) to enhance intracellular photosensitizer levels. Experimental Design Skin carcinoma cells, in-vitro and in-vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in-vivo skin tumor models (see below) were preconditioned with MTX for 72 h, then incubated with ALA for 4 h. Changes in PpIX levels and in cell survival after light exposure were assessed. Results MTX-preconditioning of monolayer cultures preferentially raised intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy, compared to PDT alone. MTX enhancement of PpIX levels was achieved over a broad MTX concentration range (0.0003 – 1.0 mg/L; 0.6 nM – 2 mM). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, i.e. ~4-fold increase in coproporphyrinogen oxidase, and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, filaggrin) were also selectively induced by MTX in carcinoma cells. In-vivo relevance was established by showing that MTX preconditioning enhances PpIX accumulation in three models: (1) organotypic cultures of immortalized keratinocytes; (2) chemically-induced skin tumors in mice; and (3) human A431 squamous cell tumors implanted subcutaneously in mice. Conclusion Combination therapy using short-term exposure to low-dose MTX followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas. PMID:19447864

  8. Retroperitoneal teratoma with somatic malignant transformation: a papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy.

    PubMed

    Zeh, Nina; Wild, Peter J; Bode, Peter K; Kristiansen, Glen; Moch, Holger; Sulser, Tullio; Hermanns, Thomas

    2013-02-12

    Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.

  9. Pituitary Carcinoma

    PubMed Central

    Cusimano, Michael D.; Ohori, Paul; Martinez, A. Julio; Jungreis, Charles; Wright, Donald C.

    1994-01-01

    The presence of distant metastases may be asymptomatic in patients who present with symptoms and signs due to the local mass effects of an invasive pituitary adenoma. A case of pituitary carcinoma in a 54-year-old man who presented with widespread asymptomatic distant metastases 12 years after initial diagnosis is reviewed. The long course and asymptomatic metastases suggested a relatively slow-growing malignancy. The factors that played a role in the pathogenesis of the metastasis are unknown. A review of the literature on pituitary carcinoma suggests that accurate diagnosis and a multidisciplinary approach to management of such lesions emphasizing surgery, radiotherapy, and hormonal manipulation may provide these patients with the longest and best quality of survival. ImagesFigure 1Figure 2Figure 3p48-bFigure 4Figure 5Figure 6 PMID:17170926

  10. Bronchiolar Carcinoma

    PubMed Central

    Quinlan, J. J.; Schaffner, V. D.; Hiltz, J. E.

    1966-01-01

    Bronchiolar carcinoma is a malignant tumour which apparently arises in a terminal bronchiole from which it spreads either by bronchial embolization or by lymphogenous and/or hematogenous dissemination. It is not a common neoplasm. Histologically, the tumour bears a striking resemblance to the disease of sheep, jagziekte, which is of virus etiology. A very common finding in reported cases is preexisting pulmonary fibrosis. At the Nova Scotia Sanatorium, Kentville, 80 cases of primary lung cancer have been encountered within the past 25 years. Six of these were bronchiolar carcinomas. Five patients had co-existing chronic pulmonary disease, bronchiectasis in one and tuberculosis in four. One patient died of a rapidly progressive bilateral lesion and five were explored. Lobectomy was done in all five, but in one for palliation only. Three patients are alive and well three, six and 14 years, respectively, after their operations. PMID:4285258

  11. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

    PubMed Central

    Sepúlveda, Ilson; Platin, Enrique; Klaassen, Rodrigo; Spencer, M. Loreto; García, Cesar; Alarcón, Ricardo; Ulloa, David

    2013-01-01

    We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program. PMID:24019781

  12. Nasopharyngeal carcinoma

    SciTech Connect

    Ho, J.H.C.

    1985-07-01

    In this editorial comment, the author presents a review of recent achievements in the diagnosis and treatment of squamous cell carcinoma of the nasopharynx. The value of the use of CT scans for differentiating between cranial nerve involvement by recurring tumors and irradiation neuropathy, and between temporal lobe irradiation encephalopathy and other nonneoplastic neurologic disorders and meningeal metastasis is discussed. Magnetic resonance imaging is said to be superior to CT for finding soft tissue involvement or abnormalities in the brain. 13 references.

  13. 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

  14. Mammographic Screening Downstages Breast Carcinomas at Time of Diagnosis: A Community-Based Experience.

    PubMed

    Parker, Robert G.; Leung, Kwan-Moon; Rees, Karen S.; Bassett, Lawrence W.; Legorreta, Antonio P.

    1999-11-01

    To determine the effectiveness of screening mammography in a community medical setting, data from a population-based, retrospective study was analyzed. Medical records of 827 patients with newly diagnosed breast cancer in California between October 1994 and March 1996 were reviewed. The primary care physician's record was abstracted for clinical history, including recommendation of screening mammography. The facility records where final diagnosis was made were abstracted for stage and treatment data. Among the patients who did not have previous screening mammography, 65.7% were diagnosed with "advanced" breast cancer (stages II, III, IV), while only 39.9% who had previous screening mammography were diagnosed with advanced breast cancer (p < 0.001). This study has reaffirmed that screening mammography of adult females generates downstaging at the time of diagnosis of breast cancer. Despite possession of a health insurance program and receiving educational materials, only 65% of patients over 50 years of age had screening mammography. As opposed to the once-a-year mailing of general reminders to all women 40 years old and older, developing a longitudinal electronic medical record in the managed care setting will support a more coordinated and individualized intervention based on age, date of last mammogram, and relative risk, among other factors. Continuing education efforts must also be directed to referring physicians, who may not yet recognize the value of screening mammography.

  15. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Argiris, Athanassios; Harrington, Kevin J.; Tahara, Makoto; Schulten, Jeltje; Chomette, Pauline; Ferreira Castro, Ana; Licitra, Lisa

    2017-01-01

    The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the “EXTREME” regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing

  16. Improved laparoscopic nephron-sparing surgery for renal cell carcinoma based on the precise anatomy of the nephron

    PubMed Central

    Guo, Gang; Cai, Wei; Zhang, Xu

    2016-01-01

    The aim of the present study was to investigate a method of laparoscopic nephron-sparing surgery (LNSS) for renal cell carcinoma (RCC) based on the precise anatomy of the nephron, and to decrease the incidence of hemorrhage and urinary leakage. Between January 2012 and December 2013, 31 patients who presented to the General Hospital of the People's Liberation Army (Beijing, China) were treated for RCC. The mean tumor size was 3.4±0.7 cm in diameter (range, 1.2–6.0 cm). During surgery, the renal artery was blocked, and subsequently, an incision in the renal capsule and renal cortex was performed, at 3–5 mm from the tumor edge. Subsequent to the incision of the renal parenchyma, scissors with blunt and sharp edge were used to separate the base of the tumor from the normal renal medulla, in the direction of the ray medullary in the renal pyramids. The basal blood vessels were incised following the hemostasis of the region using bipolar coagulation. The minor renal calyces were stripped carefully and the wound was closed with an absorbable sutures. The arterial occlusion time, duration of surgery, intraoperative bleeding volume, post-operative drainage volume, pathological results and complications were recorded. The surgery was successful for all patients. The estimated average intraoperative bleeding volume was 55.7 ml, the average surgical duration was 95.5 min, the average arterial occlusion time was 21.2 min, the average post-operative drainage volume was 92.3 ml and the average post-operative length of hospital stay was 6.1 days. No hemorrhage or urinary leakage was observed in the patients following the surgery. LNSS for RCC based on the precise anatomy of the nephron was concluded to be effective and feasible. The surgery is useful for the complete removal of tumors and guarantees a negative margin, which may also decrease the incidence of hemorrhage and urinary leakage following surgery. PMID:27895733

  17. A pilot study of SPECT/CT-based mixed-reality navigation towards the sentinel node in patients with melanoma or Merkel cell carcinoma of a lower extremity.

    PubMed

    van den Berg, Nynke S; Engelen, Thijs; Brouwer, Oscar R; Mathéron, Hanna M; Valdés-Olmos, Renato A; Nieweg, Omgo E; van Leeuwen, Fijs W B

    2016-08-01

    To explore the feasibility of an intraoperative navigation technology based on preoperatively acquired single photon emission computed tomography combined with computed tomography (SPECT/CT) images during sentinel node (SN) biopsy in patients with melanoma or Merkel cell carcinoma. Patients with a melanoma (n=4) or Merkel cell carcinoma (n=1) of a lower extremity scheduled for wide re-excision of the primary lesion site and SN biopsy were studied. Following a Tc-nanocolloid injection and lymphoscintigraphy, SPECT/CT images were acquired with a reference target (ReTp) fixed on the leg or the iliac spine. Intraoperatively, a sterile ReTp was placed at the same site to enable SPECT/CT-based mixed-reality navigation of a gamma ray detection probe also containing a reference target (ReTgp).The accuracy of the navigation procedure was determined in the coronal plane (x, y-axis) by measuring the discrepancy between standard gamma probe-based SN localization and mixed-reality-based navigation to the SN. To determine the depth accuracy (z-axis), the depth estimation provided by the navigation system was compared to the skin surface-to-node distance measured in the computed tomography component of the SPECT/CT images. In four of five patients, it was possible to navigate towards the preoperatively defined SN. The average navigational error was 8.0 mm in the sagittal direction and 8.5 mm in the coronal direction. Intraoperative sterile ReTp positioning and tissue movement during surgery exerted a distinct influence on the accuracy of navigation. Intraoperative navigation during melanoma or Merkel cell carcinoma surgery is feasible and can provide the surgeon with an interactive 3D roadmap towards the SN or SNs in the groin. However, further technical optimization of the modality is required before this technology can become routine practice.

  18. Microelectrode chip based real time monitoring of vital MCF-7 mamma carcinoma cells by impedance spectroscopy.

    PubMed

    Wolf, Peter; Rothermel, Andrée; Beck-Sickinger, Annette G; Robitzki, Andrea A

    2008-10-15

    Sensorchip based impedance spectroscopy can detect inhibitory effects of human neuropeptide Y (hNPY) on living cells in a non-invasive labelling free way in real time without the need of supporting reagents. Since the discovery that neoplasmatic transformations in breast cancer are correlated with a change of the receptor subtype expression of hNPY in the affected tissue, the hNPY receptor-ligand system has come to the fore of cancer research. Today there are different methods detecting hNPY receptor interactions like fluorescent and radioactive labelling or detecting hNPY-pathway activation like cyclic adenosine monophosphate (cAMP) and G protein-coupled receptor (GPCR)-assays. For all these assays it is necessary to either label related proteins with additional substances, which can affect the nature state of the cell, or the need of producing cell lysate which allows only a snapshot of the investigated cells. To overcome these problems we established a new method to detect hNPY-receptor interactions. Therefore, we monitor the complex electric resistance (impedance) of cells attached to a microelectrode over a wide frequency range. Cell alterations are detected as changes in the impedance spectra. After application of the adenylyl cyclase-stimulating reagent forskolin, impedance is decreased at 5 kHz frequency within minutes. This effect can be inhibited by preincubating the cells with hNPY for a time range of 20 min. The inhibitory effect of hNPY can be washed out and the same cells can be stimulated by forskolin again.

  19. Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

    PubMed

    Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

    2016-12-01

    The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

  20. Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue.

    PubMed

    van de Pol, Marjan; Levendag, Peter C; de Bree, Remco R; Franssen, Jan Huib; Smeele, Ludwig E; Nijdam, Wideke M; Jansen, Peter P; Meeuwis, Cees A; Leemans, C René

    2004-01-01

    This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.

  1. The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and (13) C-isotope based metabolomics.

    PubMed

    Darpolor, Moses M; Basu, Sankha S; Worth, Andrew; Nelson, David S; Clarke-Katzenberg, Regina H; Glickson, Jerry D; Kaplan, David E; Blair, Ian A

    2014-04-01

    Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U-(13) C6 ]glucose metabolism or [U-(13) C5 ,(15) N2 ]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non-tumor liver (p value < 0.0001). In addition, branched-chain amino acid metabolism (p value < 0.0001) and tricarboxylic acid metabolism (p value < 0.0001) are significant and differentiable. Statistical analysis of measurable NMR metabolites indicated that at least two of the group means were significantly different for the metabolites alanine (p value = 0.0013), succinate (p value = 0.0001), lactate (p value = 0.0114), glycerophosphoethanolamine (p value = 0.015), and inorganic phosphate (p value = 0.0001). However, (13) C isotopic enrichment analysis of these metabolites revealed less than 50% isotopic enrichment with either stable [U-(13) C6 ]glucose metabolism or [U-(13) C5 ,(15) N2 ]glutamine. This may indicate the differential account of total metabolite pool versus de novo metabolites from a (13) C labeled substrate. The ultimate translation of these findings will be to determine putative enzyme activity via

  2. Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening.

    PubMed

    Chen, Yufeng; Zhao, Weilin; Lin, Longde; Xiao, Xue; Zhou, Xiaoying; Ming, Huixin; Huang, Tingting; Liao, Jian; Li, Yancheng; Zeng, Xiaoyun; Huang, Guangwu; Ye, Weimin; Zhang, Zhe

    2015-01-01

    Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening

  3. Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study

    PubMed Central

    2010-01-01

    Introduction Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC incidence, relative survival, and associated cancer risk in the United States. Methods Using data from the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), and relative survival for breast-ACC, and standardized incidence ratios (SIRs) for other cancers. Results Overall 338 women (IR = 0.92/1 million person-years) were diagnosed with breast-ACC during 1977 to 2006. Blacks had 39% lower IRs than Whites (IRR = 0.61, 95% confidence interval = 0.37 to 0.96), and IRs remained constant over the 30-year period. Ninety-five percent of cases presented with localized stage (n = 320; IR = 0.87), and the highest IRs were observed for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative tumors (IR = 0.56). Like other typically ER-negative tumors, age-specific IRs increased until midlife and then plateaued. Five-year, 10-year, and 15-year relative survival was 98.1%, 94.9%, and 91.4%, respectively. The risk of female breast cancer was not increased following (SIR = 0.89, 95% confidence interval = 0.43 to 1.64) or preceding (SIR = 0.71, 95% confidence interval = 0.28 to 1.46) breast-ACC. Similarly, no association was observed for breast-ACC and risk of all other cancers combined, solid tumors, or lymphohematopoietic malignancies. Conclusions Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and lend credence to the apparent heterogeneity of basal-like breast cancers. PMID:20653964

  4. Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?

    PubMed

    Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao

    2016-01-01

    "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.

  5. An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival.

    PubMed

    Lu, Cheng; Lewis, James S; Dupont, William D; Plummer, W Dale; Janowczyk, Andrew; Madabhushi, Anant

    2017-08-04

    Oral cavity squamous cell carcinoma is the most common type of head and neck carcinoma. Its incidence is increasing worldwide, and it is associated with major morbidity and mortality. It is often unclear which patients have aggressive, treatment refractory tumors vs those whose tumors will be more responsive to treatment. Better identification of patients with high- vs low-risk cancers could help provide more tailored treatment approaches and could improve survival rates while decreasing treatment-related morbidity. This study investigates computer-extracted image features of nuclear shape and texture on digitized images of H&E-stained tissue sections for risk stratification of oral cavity squamous cell carcinoma patients compared with standard clinical and pathologic parameters. With a tissue microarray cohort of 115 retrospectively identified oral cavity squamous cell carcinoma patients, 50 were randomly chosen as the modeling set, and the remaining 65 constituted the test set. Following nuclear segmentation and feature extraction, the Wilcoxon rank sum test was used to identify the five most prognostic quantitative histomorphometric features from the modeling set. These top ranked features were then combined via a machine learning classifier to construct the oral cavity histomorphometric-based image classifier (OHbIC). The classifier was then validated for its ability to risk stratify patients for disease-specific outcomes on the test set. On the test set, the classifier yielded an area under the receiver operating characteristic curve of 0.72 in distinguishing disease-specific outcomes. In univariate survival analysis, high-risk patients predicted by the classifier had significantly poorer disease-specific survival (P=0.0335). In multivariate analysis controlling for T/N-stage, resection margins, and smoking status, positive classifier results were independently predictive of poorer disease-specific survival: hazard ratio (95% confidence interval)=11.023 (2

  6. 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

  7. 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.

  8. S-1-Based Chemotherapy versus Capecitabine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Carcinoma: A Meta-Analysis

    PubMed Central

    Wang, Zhi-qiang; Zhang, Dong-sheng; Luo, Hui-yan; Qiu, Miao-zhen; Wang, Feng-hua; Ren, Chao; Zeng, Zhao-lei; Xu, Rui-hua

    2013-01-01

    Background Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. Methods PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. Results Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There’re no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed. Conclusion S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared

  9. Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

    PubMed

    Pezzi, Todd A; Mohamed, Abdallah S R; Sheu, Tommy; Blanchard, Pierre; Sandulache, Vlad C; Lai, Stephen Y; Cabanillas, Maria E; Williams, Michelle D; Pezzi, Christopher M; Lu, Charles; Garden, Adam S; Morrison, William H; Rosenthal, David I; Fuller, Clifton D; Gunn, G Brandon

    2017-05-01

    The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718-0.988; 45-59.9 Gy: HR, 0.596; 95% CI, 0.479-0.743; 60-75 Gy: HR, 0.419; 95% CI, 0.339-0.517) correlated with OS. The RT dose-survival correlation for patients who received higher (60-75 Gy) versus lower (45-59.9 Gy) therapeutic doses was confirmed by propensity-score matching. Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653-1661. © 2017 American Cancer Society. © 2016 American Cancer Society.

  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. Effectiveness of an (18)F-FDG-PET based strategy to optimize the diagnostic trajectory of suspected recurrent laryngeal carcinoma after radiotherapy: The RELAPS multicenter randomized trial.

    PubMed

    de Bree, Remco; van der Putten, Lisa; van Tinteren, Harm; Wedman, Jan; Oyen, Wim J G; Janssen, Luuk M; van den Brekel, Michiel W M; Comans, Emile F I; Pruim, Jan; Takes, Robert P; Hobbelink, Monique G G; Valdés Olmos, Renato; van der Laan, Bernard F A M; Boers, Maarten; Hoekstra, Otto S; Leemans, C René

    2016-02-01

    The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found. In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment. Copyright © 2015 Elsevier

  12. Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma.

    PubMed

    Endo, Kazuhira; Ueno, Takayoshi; Kondo, Satoru; Wakisaka, Naohiro; Murono, Shigeyuki; Ito, Makoto; Kataoka, Kazunori; Kato, Yasuki; Yoshizaki, Tomokazu

    2013-03-01

    Cisplatin (CDDP) has been a key drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity is one of its adverse reactions that are dose limiting. To increase its antitumor effects and reduce such toxicity problems, polymeric micelles carrying CDDP (NC-6004) have been developed. The present study was designed to evaluate the efficacy and safety of NC-6004 for oral squamous cell carcinoma. In vitro antitumor activity was assayed in four oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of NC-6004, nude mice bearing OSC-19 were administered NC-6004 or CDDP. The in vitro growth-inhibitory effect of NC-6004 was significantly less than that of CDDP. However, both NC-6004 and CDDP showed equivalent antitumor effects in vivo. Mice with CDDP developed renal cell apoptosis; however, those injected with NC-6004 were almost free of renal cell injury. Moreover, in an orthotopic tongue cancer model using OSC-19, NC-6004 reduced the rate of sentinel lymph node metastasis to lower than that with CDDP. In conclusion, considering the potential advantages in terms of noticeable antitumor activity, lymphatic drug delivery and reduced nephrotoxicity, NC-6004 represents a significant structural improvement in the development of a platinum complex. © 2012 Japanese Cancer Association.

  13. Carcinoma gallbladder.

    PubMed

    Biswas, P K

    2010-07-01

    Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

  14. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline.

    PubMed

    Stratigos, Alexander; Garbe, Claus; Lebbe, Celeste; Malvehy, Josep; del Marmol, Veronique; Pehamberger, Hubert; Peris, Ketty; Becker, Jürgen C; Zalaudek, Iris; Saiag, Philippe; Middleton, Mark R; Bastholt, Lars; Testori, Alessandro; Grob, Jean-Jacques

    2015-09-01

    Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert's experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF-EADO-EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck

  15. Ameloblastic fibroma: a stage in the development of a hamartomatous odontoma or a true neoplasm? Critical analysis of 162 previously reported cases plus 10 new cases.

    PubMed

    Buchner, Amos; Vered, Marilena

    2013-11-01

    To analyze neoplastic and hamartomatous variants of ameloblastic fibromas (AFs). Analysis of 172 cases (162 previously reported, 10 new). AF emerged as a lesion primarily of children and adolescents (mean age, 14.9 years), with about 80% diagnosed when odontogenesis is completed (age, < 22 years). Around 28% of all AFs were small and asymptomatic, and 72% exhibited moderate-to-severe bone expansion. There are 2 variants of AF: neoplastic and hamartomatous. Lesions in patients aged >22 years are considered true neoplasms, while those in younger patients may be either true neoplasms or odontomas in early stages of development. Although the histopathology of hamartomatous and neoplastic variants of AF are indistinguishable, clinical and radiologic features can be of some help to distinguish between them. Asymptomatic small unilocular lesions with no or minimal bone expansion in young individuals are likely to be developing odontomas, and large, expansile lesions with extensive bone destruction are neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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

  18. HbA1c-Based Score Model for Predicting Death Risk in Patients with Hepatocellular Carcinoma and Type 2 Diabetes Mellitus.

    PubMed

    He, Lingling; Zhang, Shuan; Liu, Xiaoli; Jiang, Yuyong; Wang, Xianbo; Yang, Zhiyun

    2017-01-01

    Aim. To establish a new score model to predict risk of death in patients with hepatocellular carcinoma and type 2 diabetes mellitus. Methods. This was a retrospective study of 147 patients with hepatocellular carcinoma and type 2 diabetes mellitus who came to Beijing Ditan Hospital between October 2008 and June 2013. Univariate and multivariate logistic regression analysis was performed to obtain the independent factors associated with death risk. A new score model was devised according to these factors. Results. A prediction score model composed of HbA1c, NLR, age, and CTP class was devised, which ranged from 0 to 7. AUROC of the score was 0.853 (P < 0.001, 95% CI: 0.791-0.915). Scores 0-2, 3-4, and 5-7 identified patients as low-, medium-, and high-risk categories. The cumulative survival rate was 93.6%, 83.0%, and 74.5% in the low-risk group in 1, 2, and 3 years, while it was 64.0%, 46.0%, and 26.0% in the medium-risk group, whereas it was 24.0%, 12.0%, and 6.0% in the high-risk group, respectively. The cumulative survival rate was significantly higher in the low-risk group than that in the medium-risk group and high-risk group (P < 0.001). Conclusion. The HbA1c-based score model can be used to predict death risk in patients with hepatocellular carcinoma and type 2 diabetes mellitus.

  19. 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

  20. 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.

  1. 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.

  2. Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma

    PubMed Central

    Beumer, H. Wolfgang; Puscas, Liana; Afshari, Hamid R.; Esclamado, Ramon M.; Scher, Richard; Fisher, Samuel; Lo, Justin; Mulvey, Christine; Ramanujam, Nirmala; Lee, Walter T.

    2014-01-01

    SUMMARY Objectives We propose the use of morphological optical biomarkers for rapid detection of human head and neck squamous cell carcinoma (HNSCC) by leveraging the underlying tissue characteristics in aerodigestive tracts. Materials and Methods Diffuse reflectance spectra were obtained from malignant and contra-lateral normal tissues of 57 patients undergoing panendoscopy and biopsy. Oxygen saturation, total hemoglobin concentration, and the reduced scattering coefficient were extracted. Differences in malignant and normal tissues were examined based on two different groupings: anatomical site and morphological tissue type. Results and Conclusions Measurements were acquired from 252 sites, of which 51 were pathologically classified as SCC. Optical biomarkers exhibited statistical differences between malignant and normal samples. Contrast was enhanced when parsing tissues by morphological classification rather than anatomical subtype for unpaired comparisons. Corresponding linear discriminant models using multiple optical biomarkers showed improved predictive ability when accounting for morphological classification, particularly in node-positive lesions. The false-positive rate was retrospectively found to decrease by 34.2% in morphologically- vs. anatomically-derived predictive models. In glottic tissue, the surgeon exhibited a false-positive rate of 45.7% while