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1. Langfort R, Rudziński P, Burakowska B: [Pulmonary neuroendocrine tumors. The spectrum of histologic subtypes and current concept on diagnosis and treatment]. Pneumonol Alergol Pol; 2010;78(1):33-46
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  • [Title] [Pulmonary neuroendocrine tumors. The spectrum of histologic subtypes and current concept on diagnosis and treatment].
  • Neuroendocrine tumors of the lung represent a broad spectrum of morphologic types that share specific morphologic, immunohistochemical, ultrastructural, and molecular characteristics.
  • The classification of neuroendocrine lung tumors has changed over the last decades and currently four categories are distinguished: typical carcinoid tumor, atypical carcinoid tumor, large cell neuroendocrine carcinoma and small cell carcinoma.
  • Neuroendocrine tumors of the lung comprise approximately 20% of all primary lung cancers.
  • Because of differences in clinical behavior, therapy, and prognosis, a reliable histological diagnosis, as well as clinical and pathological staging system are essential for an appropriate medical proceedings.
  • The most effective treatment of bronchial carcinoids and large cell neuroendocrine carcinoma in an early stage is complete surgical resection, whereas chemotherapy remains the primary treatment for small cell carcinoma.
  • The majority of patients with pulmonary carcinoid have an excellent survival, even if they present with lymph node metastases.
  • Large cell neuroendocrine and small cell carcinoma progress rapidly and are generally widespread at the moment of diagnosis.
  • Increased knowledge about pulmonary neuroendocrine tumors biology and the genetic characteristics, imply that carcinoid tumors appear to have a different etiology and pathogenesis than large cell neuroendocrine and small cell carcinoma.
  • In practice, it could be easiest to conceptualize this group of pulmonary tumors as a spectrum of malignancy ranging from the low grade typical carcinoid to the highly malignant large cell neuroendocrine and small cell carcinoma.
  • Typical carcinoid tumors associated with a fairly benign behavior should be classified as low-grade neuroendocrine tumor/carcinoma (G1) and atypical carcinoid tumors as intermediate-grade tumor/carcinoma (G2).
  • Whereas, large cell neuroendocrine and small cell carcinoma should be grouped together under the designation of high-grade neuroendocrine tumor/carcinoma (G3).
  • [MeSH-major] Lung Neoplasms / diagnosis. Lung Neoplasms / therapy. Neuroendocrine Tumors / diagnosis. Neuroendocrine Tumors / therapy
  • [MeSH-minor] Carcinoid Tumor / diagnosis. Carcinoid Tumor / therapy. Carcinoma, Large Cell / diagnosis. Carcinoma, Large Cell / therapy. Carcinoma, Small Cell / diagnosis. Carcinoma, Small Cell / therapy. Humans. Lung / pathology. Lymphatic Metastasis. Neoplasm Staging. Prognosis. Survival Analysis

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  • (PMID = 20162517.001).
  • [ISSN] 0867-7077
  • [Journal-full-title] Pneumonologia i alergologia polska
  • [ISO-abbreviation] Pneumonol Alergol Pol
  • [Language] pol
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Poland
  • [Number-of-references] 67
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2. Rossi G, Cavazza A, Marchioni A, Migaldi M, Bavieri M, Facciolongo N, Petruzzelli S, Longo L, Tamberi S, Crinò L: Kit expression in small cell carcinomas of the lung: effects of chemotherapy. Mod Pathol; 2003 Oct;16(10):1041-7
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  • [Title] Kit expression in small cell carcinomas of the lung: effects of chemotherapy.
  • A significant number of small cell lung carcinomas shows overexpression of the proto-oncogene c-kit product, a tyrosine kinase known as Kit or CD117.
  • This molecular pathway seems somewhat implicated in promoting the neoplastic growth of small cell lung carcinoma.
  • The current pharmacological availability of its selective inhibitor, together with the promising clinical results in the management of CD117-positive neoplasms such as advanced gastrointestinal stromal tumors, aroused great interest among oncologists in also adopting this therapeutic strategy in other CD117-positive tumors.
  • We evaluated a series of 27 small cell lung carcinomas, comparing the expression of CD117 of the primary naïve tumor (before first-line chemotherapy) with the expression of the same neoplasm after postchemotherapy relapse.
  • No originally CD117-negative small cell carcinomas displayed immunoreactivity after chemotherapy.
  • CD117 expression was not statistically correlated with overall survival, occurrence of chemoresistance, or clinical response to chemotherapy.
  • We also evaluated CD117 expression in a series of 46 surgically resected non-small cell lung carcinomas (8 squamous cell carcinomas, 10 adenocarcinomas, 5 pleomorphic carcinomas, 10 typical and 3 atypical carcinoids, and 10 large cell neuroendocrine carcinomas).
  • Apart from small cell carcinomas, CD117 overexpression was observed in 6 of 10 large cell neuroendocrine carcinomas, whereas all the other histotypes resulted unstained.
  • We speculate that loss of CD117 expression after chemotherapy in a high proportion of SCLC indicates that in this tumor, Kit unlikely represents the product of a constitutive mutation, as instead shown in gastrointestinal stromal tumors.
  • Keeping this finding in mind, oncologists could re-test CD117 expression in relapsing small cell lung carcinomas in order to establish the best candidates for enrollment in ongoing clinical trials with Kit inhibitors.
  • Practically speaking, CD117 may be helpful in discriminating between pulmonary high-grade neuroendocrine tumors and other histotypes, but pathologists should be aware that treated small cell lung carcinomas may remain unstained in a not insignificant number of cases.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Small Cell / drug therapy. Carcinoma, Small Cell / metabolism. Lung Neoplasms / drug therapy. Lung Neoplasms / metabolism. Proto-Oncogene Proteins c-kit / metabolism

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  • (PMID = 14559988.001).
  • [ISSN] 0893-3952
  • [Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • [ISO-abbreviation] Mod. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; Q20Q21Q62J / Cisplatin
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3. Lim E, Yap YK, De Stavola BL, Nicholson AG, Goldstraw P: The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors. J Thorac Cardiovasc Surg; 2005 Oct;130(4):969-72
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  • [Title] The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors.
  • OBJECTIVE: In pulmonary neuroendocrine tumors the realization that the extent of nodal disease is related to cell type has led to a controversy as to which is the dominant prognostic factor, stage or morphology.
  • METHODS: This is a historical cohort study of patients with confirmed pulmonary neuroendocrine tumors who underwent lung resection from 1980 through 2003.
  • The cell types for the 177 eligible patients were typical carcinoid in 89 (50%), atypical carcinoid in 15 (8%), large cell in 22 (13%), and small cell in 51 (29%).
  • The median time to follow-up was 7 years (first to third quartile, 2-12 years), and overall 5- and 10-year survivals were 86% (79%-90%) and 81% (74%-87%), respectively.
  • The univariable predictors of survival were age (P = .001), nodal stage (P = .01), and cell type (P < .001).
  • In the final multivariable model only age (P = .04) and cell type (P < .001) remained as independent predictors.
  • The hazard of death among patients with large cell or small cell lung cancer was highest in the first year and a half after diagnosis, reducing drastically thereafter.
  • CONCLUSIONS: In pulmonary neuroendocrine tumors cell type is the predominant determinant of survival.
  • The survival of patients with each cell type is sufficiently diverse to warrant different management strategies.
  • Conservative resection is feasible for typical carcinoids, but the effects of adjuvant chemotherapy need to be evaluated for the other subgroups.
  • [MeSH-major] Lung Neoplasms / mortality. Lung Neoplasms / pathology. Neuroendocrine Tumors / mortality. Neuroendocrine Tumors / pathology
  • [MeSH-minor] Cohort Studies. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis. Retrospective Studies. Survival Rate

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  • (PMID = 16214506.001).
  • [ISSN] 1097-685X
  • [Journal-full-title] The Journal of thoracic and cardiovascular surgery
  • [ISO-abbreviation] J. Thorac. Cardiovasc. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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4. Igawa S, Watanabe R, Ito I, Murakami H, Takahashi T, Nakamura Y, Tsuya A, Kaira K, Naito T, Endo M, Yamamoto N, Kameya T: Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer; 2010 Jun;68(3):438-45
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  • [Title] Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer.
  • BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) shares several features with small cell lung carcinoma (SCLC).
  • While the diagnosis of LCNEC by biopsy specimens is challenging, a definitive diagnosis of this highly malignant tumor is critical in unresectable cases to determine the optimal therapeutic strategy.
  • The objective of this study was to assess the efficacy of chemotherapy for unresectable high-grade non-small cell neuroendocrine carcinoma (HNSCNEC) called by us, which likely includes most LCNECs except for combined types, and to compare the efficacy of chemotherapy for HNSCNEC, with that for extended disease SCLC (ED-SCLC).
  • We simultaneously evaluated the clinical response to the chemotherapy and survival time of the 14 HNSCNEC and 77 ED-SCLC patients.
  • RESULTS: The chemotherapy regimens in the 14 patients with unresectable HNSCNEC were platinum-based combination regimens or irinotecan or vinorelbine or docetaxel alone.
  • The chemotherapy regimens in the 77 patients with ED-SCLC were platinum-based combination regimens.
  • We assessed an objective response rate, a one-year survival rate, and median survival time as 50% (7/14), 34% and 10 months, respectively, in the 14 HNSCNEC patients, and as 53% (41/77), 48% and 12.3 months, respectively, in the 77 ED-SCLC patients.
  • CONCLUSION: The clinical efficacy of chemotherapy for unresectable HNSCNECs, including most LCNECs, is comparable to that for ED-SCLC.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / drug therapy. Lung Neoplasms / drug therapy. Neuroendocrine Tumors / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Camptothecin / administration & dosage. Camptothecin / adverse effects. Camptothecin / analogs & derivatives. Disease Progression. Drug Therapy, Combination. Female. Humans. Immunohistochemistry. Male. Middle Aged. Neoplasm Staging. Platinum Compounds / administration & dosage. Platinum Compounds / adverse effects. Survival Analysis. Taxoids / administration & dosage. Taxoids / adverse effects. Vinblastine / administration & dosage. Vinblastine / adverse effects. Vinblastine / analogs & derivatives

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  • [Copyright] Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
  • (PMID = 19699548.001).
  • [ISSN] 1872-8332
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Platinum Compounds; 0 / Taxoids; 15H5577CQD / docetaxel; 5V9KLZ54CY / Vinblastine; 7673326042 / irinotecan; Q6C979R91Y / vinorelbine; XT3Z54Z28A / Camptothecin
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5. Gilbert JA, Frederick LM, Ames MM: The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res; 2000 Nov;6(11):4365-72
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  • [Title] The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells.
  • The carcinoid tumor is an uncommon neuroendocrine neoplasm the hallmark of which is excessive serotonin production.
  • Here, we report Western and Northern analyses detecting large quantities of AAAD polypeptide and mRNA in human carcinoid primary as well as metastatic tumors compared with normal surrounding tissues.
  • To assess the feasibility of targeting these high AAAD levels for chemotherapy, AAAD inhibitors carbidopa (alpha-methyl-dopahydrazine), alpha-monofluoromethyldopa (MFMD), and 3-hydroxybenzylhydrazine (NSD-1015) were incubated (72 h) with NCI-H727 human lung carcinoid cells.
  • On exposure to other human tumor lines, carbidopa was lethal only to NCI-H146 and NCI-H209 small cell lung carcinoma (SCLC) lines (IC50 = 12 +/- 1 microM and 22 +/- 5 microM, respectively).
  • Carbidopa (100 microM) decreased growth of (but did not kill) SK-N-SH neuroblastoma and A204 rhabdomyosarcoma cells and did not affect proliferation of DU 145 prostate, MCF7 breast, or NCI-H460 large cell lung carcinoma lines.
  • For lung tumor lines (carcinoid, two SCLC, and one large cell lung carcinoma), AAAD activity was correlated with the potency of carbidopa-induced cytotoxicity.
  • [MeSH-major] Aromatic Amino Acid Decarboxylase Inhibitors. Carbidopa / pharmacology. Carcinoid Tumor / drug therapy. Carcinoma, Small Cell / drug therapy. Enzyme Inhibitors / pharmacology. Lung Neoplasms / drug therapy
  • [MeSH-minor] Cell Division / drug effects. Humans. Ileum / enzymology. Liver / enzymology. Microscopy, Electron. Tumor Cells, Cultured

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  • (PMID = 11106255.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 58450
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Aromatic Amino Acid Decarboxylase Inhibitors; 0 / Enzyme Inhibitors; MNX7R8C5VO / Carbidopa
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6. Iyoda A, Hiroshima K, Toyozaki T, Haga Y, Baba M, Fujisawa T, Ohwada H: Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. Cancer; 2001 Sep 1;92(5):1108-12
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  • [Title] Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.
  • BACKGROUND: In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma, large cell carcinoma with neuroendocrine differentiation, and large cell carcinoma with neuroendocrine morphology as a variant of large cell carcinoma.
  • Patients with large cell carcinoma with neuroendocrine features have poor prognoses, comparable to those for small cell lung carcinoma.
  • Small cell lung carcinoma is sensitive to chemotherapy; however, it is still unclear whether large cell carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy.
  • METHODS: The authors analyzed 73 patients with large cell carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.
  • RESULTS: In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small cell lung carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy.
  • In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy.
  • CONCLUSIONS: Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with large cell carcinoma with neuroendocrine features in early stage.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Large Cell / drug therapy. Carcinoma, Large Cell / pathology. Lung Neoplasms / drug therapy. Lung Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Carboplatin / administration & dosage. Carcinoma, Neuroendocrine. Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Cyclophosphamide / administration & dosage. Female. Humans. Male. Middle Aged. Neoplasm Staging. Pneumonectomy. Retrospective Studies. Survival Analysis

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  • [Copyright] Copyright 2001 American Cancer Society.
  • (PMID = 11571722.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 8N3DW7272P / Cyclophosphamide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin
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7. Massoni Neto LM, Bianchi CP, Ab'Saber AM, Parra ER, Takagaki T, Pereira JC, Soares FA, Leite K, Capelozzi VL: p53 immunostaining is correlated with reduced survival and is not correlated with gene mutations in resected pulmonary large cell carcinomas. Braz J Med Biol Res; 2007 Aug;40(8):1045-53
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  • [Title] p53 immunostaining is correlated with reduced survival and is not correlated with gene mutations in resected pulmonary large cell carcinomas.
  • Malignancy of pulmonary large cell carcinomas (LCC) increases from classic LCC through LCC with neuroendocrine morphology (LCCNM) to large cell neuroendocrine carcinomas (LCNEC).
  • Because the malignancy of LCC is highly dependent on proteins with functions in the cell cycle, DNA repair, and apoptosis, p53 has been targeted as a potentially useful biological marker. p53 mutations in lung cancers have been shown to result in expression and protein expression also occurs in the absence of mutations.
  • To validate the importance of both p53 protein expression (by immunostaining) and p53 gene mutations in lung LCC (by PCR-single strand conformational polymorphism analysis of exons 5, 6, 7, and 8) and to study their relationships with clinical factors and sub-classification we investigated the correlation of p53 abnormalities in 15 patients with LCC (5 classic LCC, 5 LCNEC, and 5 LCCNM) who had undergone resection with curative intent.
  • After adjustment for stage, age, gender, chemotherapy, radiotherapy, and histological subtypes by multivariate analysis, p53 expression had an independent impact on survival.

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  • (PMID = 17665040.001).
  • [ISSN] 0100-879X
  • [Journal-full-title] Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
  • [ISO-abbreviation] Braz. J. Med. Biol. Res.
  • [Language] ENG
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Brazil
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Neoplasm; 0 / Tumor Suppressor Protein p53
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8. Rossi G, Cavazza A, Marchioni A, Longo L, Migaldi M, Sartori G, Bigiani N, Schirosi L, Casali C, Morandi U, Facciolongo N, Maiorana A, Bavieri M, Fabbri LM, Brambilla E: Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol; 2005 Dec 1;23(34):8774-85
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  • [Title] Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung.
  • PURPOSE: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results.
  • Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets.
  • PATIENTS AND METHODS: We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRalpha, PDGFRbeta, and Met.
  • At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001).
  • CONCLUSION: Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide-based chemotherapy.
  • Patients who received this therapy had the best survival rate.
  • Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRalpha, PDGFRbeta, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Large Cell / drug therapy. Carcinoma, Neuroendocrine / drug therapy. Lung Neoplasms / drug therapy. Receptor Protein-Tyrosine Kinases / biosynthesis
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Carboplatin / administration & dosage. Carcinoma, Small Cell / drug therapy. Carcinoma, Small Cell / enzymology. Carcinoma, Small Cell / mortality. Cisplatin / administration & dosage. DNA Mutational Analysis. Deoxycytidine / administration & dosage. Deoxycytidine / analogs & derivatives. Female. Follow-Up Studies. Humans. Immunohistochemistry. Male. Middle Aged. Multivariate Analysis. Neoplasm Staging. Paclitaxel / administration & dosage. Polymerase Chain Reaction. Proto-Oncogene Proteins c-kit / biosynthesis. Proto-Oncogene Proteins c-kit / genetics. Proto-Oncogene Proteins c-met / biosynthesis. Proto-Oncogene Proteins c-met / genetics. Receptor, Platelet-Derived Growth Factor alpha / biosynthesis. Receptor, Platelet-Derived Growth Factor alpha / genetics. Receptor, Platelet-Derived Growth Factor beta / biosynthesis. Receptor, Platelet-Derived Growth Factor beta / genetics. Survival Analysis. Survival Rate. Treatment Outcome

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  • (PMID = 16314638.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine; BG3F62OND5 / Carboplatin; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; EC 2.7.10.1 / Proto-Oncogene Proteins c-met; EC 2.7.10.1 / Receptor Protein-Tyrosine Kinases; EC 2.7.10.1 / Receptor, Platelet-Derived Growth Factor alpha; EC 2.7.10.1 / Receptor, Platelet-Derived Growth Factor beta; P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin
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9. Hage R, Seldenrijk K, de Bruin P, van Swieten H, van den Bosch J: Pulmonary large-cell neuroendocrine carcinoma (LCNEC). Eur J Cardiothorac Surg; 2003 Apr;23(4):457-60
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  • [Title] Pulmonary large-cell neuroendocrine carcinoma (LCNEC).
  • OBJECTIVE: The experiences on the treatment of seven consecutive patients with large-cell neuroendocrine carcinoma (LCNEC) were studied, observed over 6 years from 1992.
  • Together with the carcinoids (atypical and typical) and the small-cell lung carcinoma (SCLC), it forms the spectrum of neuroendocrine tumors.
  • Three patients received adjuvant chemotherapy and one, adjuvant radiotherapy.
  • CONCLUSIONS: LCNEC is a high-grade neuroendocrine tumor with a poor prognosis.
  • In our patients, after surgical resection or multimodality treatment, all have developed widespread metastatic disease with a rapidly fatal course.
  • Due to the rarity of this tumor, the incidence, prognosis and optimal treatment remain to be determined.
  • [MeSH-major] Carcinoma, Large Cell / surgery. Carcinoma, Neuroendocrine / surgery. Lung Neoplasms / surgery
  • [MeSH-minor] Aged. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Staging. Retrospective Studies. Treatment Outcome

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  • [CommentIn] Eur J Cardiothorac Surg. 2003 Oct;24(4):671-2; author reply 672-3 [14500107.001]
  • (PMID = 12694759.001).
  • [ISSN] 1010-7940
  • [Journal-full-title] European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
  • [ISO-abbreviation] Eur J Cardiothorac Surg
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 13
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10. Nagasaki T, Tsuchiya T, Tagawa T, Honda S, Yamasaki N, Miyazaki T, Hidaka S, Hayashi T, Nagayasu T: Analysis of 5-fluorouracil-related enzymes in pulmonary neuroendocrine carcinoma: differences in biological properties compared to epithelial carcinoma. Clin Lung Cancer; 2010 Nov 1;11(6):412-22
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  • [Title] Analysis of 5-fluorouracil-related enzymes in pulmonary neuroendocrine carcinoma: differences in biological properties compared to epithelial carcinoma.
  • Few data are available on these enzymes in pulmonary neuroendocrine carcinoma, because 5-FU appears to have minimal effect on such carcinomas.
  • PATIENTS AND METHODS: This study investigated 5-FU-related enzymes in large-cell neuroendocrine carcinoma (LCNEC; n = 31) and small-cell lung carcinoma (SCLC; n = 15), comparing expression levels with epithelial carcinomas including adenocarcinoma (ADC; n = 34) and squamous cell carcinoma (SCC; n = 13) obtained from 93 patients with primary lung tumors.
  • When we divide the data by pathology into epithelial carcinoma and neuroendocrine carcinoma, malignant potentials and prognoses correlated with mRNA levels in epithelial carcinoma, but not in neuroendocrine carcinoma.
  • Immunohistochemically, neuroendocrine carcinomas were immunonegative for DPD.
  • CONCLUSION: Neuroendocrine carcinomas show characteristic patterns of expression for 5-FU-related enzymes, including low DPD mRNA and protein level and high TS mRNA level compared with adenocarcinomas.
  • These results partially explain why 5-FU-based chemotherapy shows minimal efficacy against SCLC.
  • Conversely, clinicopathological data and survival analysis indicates that 5-FU-related enzymes themselves might not affect the malignant potential of neuroendocrine carcinoma.
  • Expressional differences in 5-FU-related enzymes among pathologies may provide valuable information for tailor-made chemotherapy.
  • [MeSH-major] Dihydrouracil Dehydrogenase (NADP) / genetics. Lung Neoplasms / enzymology. Orotate Phosphoribosyltransferase / genetics. Thymidylate Synthase / genetics
  • [MeSH-minor] Adenocarcinoma / drug therapy. Adenocarcinoma / enzymology. Aged. Antimetabolites, Antineoplastic / pharmacology. Carcinoma, Large Cell / drug therapy. Carcinoma, Large Cell / enzymology. Carcinoma, Neuroendocrine / drug therapy. Carcinoma, Neuroendocrine / enzymology. Carcinoma, Small Cell / drug therapy. Carcinoma, Small Cell / enzymology. Carcinoma, Squamous Cell / drug therapy. Carcinoma, Squamous Cell / enzymology. Drug Resistance, Neoplasm. Female. Fluorouracil / pharmacology. Gene Expression Regulation, Neoplastic. Humans. Male. RNA, Messenger / metabolism. Retrospective Studies

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  • (PMID = 21062732.001).
  • [ISSN] 1938-0690
  • [Journal-full-title] Clinical lung cancer
  • [ISO-abbreviation] Clin Lung Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / RNA, Messenger; EC 1.3.1.2 / Dihydrouracil Dehydrogenase (NADP); EC 2.1.1.45 / Thymidylate Synthase; EC 2.4.2.10 / Orotate Phosphoribosyltransferase; U3P01618RT / Fluorouracil
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11. Kozuki T, Fujimoto N, Ueoka H, Kiura K, Fujiwara K, Shiomi K, Mizobuchi K, Tabata M, Hamazaki S, Tanimoto M: Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol; 2005 Mar;131(3):147-51
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  • [Title] Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma.
  • PURPOSE: According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma.
  • The objective of this study was to investigate the treatment strategy for LCNEC.
  • Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR.
  • Of five patients with gefitinib as salvage therapy, one achieved PR.
  • To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease.
  • In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Large Cell / therapy. Lung Neoplasms / therapy. Neoplasm Recurrence, Local / therapy. Neuroendocrine Tumors / therapy
  • [MeSH-minor] Adult. Aged. Biomarkers, Tumor / blood. Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Etoposide / administration & dosage. Female. Humans. Male. Middle Aged. Neoplasm Staging. Quinazolines / administration & dosage. Radiotherapy, Adjuvant. Retrospective Studies. Treatment Failure. Treatment Outcome

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  • (PMID = 15538626.001).
  • [ISSN] 0171-5216
  • [Journal-full-title] Journal of cancer research and clinical oncology
  • [ISO-abbreviation] J. Cancer Res. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Quinazolines; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; S65743JHBS / gefitinib
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12. Papotti M, Cassoni P, Sapino A, Passarino G, Krueger JE, Albores-Saavedra J: Large cell neuroendocrine carcinoma of the gallbladder: report of two cases. Am J Surg Pathol; 2000 Oct;24(10):1424-8
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  • [Title] Large cell neuroendocrine carcinoma of the gallbladder: report of two cases.
  • We report two cases of primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder, which, to the best of our knowledge, represent the first description of this entity.
  • One of the tumors consisted entirely of LCNEC, whereas the second tumor was composed of LCNEC and the more common intestinal-type adenocarcinoma.
  • Both tumors were morphologically similar to their pulmonary counterpart and were characterized by large cells with prominent nucleoli, coarse chromatin, and a high mitotic rate.
  • Panendocrine markers were expressed in a variable proportion of tumor cells in both cases, and one of the cases also showed focal positivity for type 2 somatostatin receptors.
  • One of the tumors followed a rapidly fatal course despite aggressive surgical treatment and chemotherapy administration, and the second patient is still alive and disease-free 12 months after surgery.
  • From an academic standpoint, we now know that all the neuroendocrine tumors described in other organs can arise de novo in the gallbladder.
  • More importantly, however, the recognition of this rare tumor type carries important clinical implications in regard to the use of chemotherapeutic agents and supplemental treatments (for example, somatostatin analogs).
  • [MeSH-major] Carcinoma, Large Cell / secondary. Carcinoma, Neuroendocrine / secondary. Gallbladder Neoplasms / pathology
  • [MeSH-minor] Aged. Biomarkers, Tumor / analysis. Cholelithiasis / etiology. Cholelithiasis / pathology. Cholelithiasis / surgery. Chromogranin A. Chromogranins / analysis. Fatal Outcome. Humans. Immunoenzyme Techniques. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Liver Neoplasms / surgery. Male. Middle Aged. Neoplasm Proteins / analysis. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / pathology. Synaptophysin / analysis

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  • (PMID = 11023106.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Chromogranin A; 0 / Chromogranins; 0 / Neoplasm Proteins; 0 / Synaptophysin
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13. Francia G, Davì MV, Montresor E, Colato C, Ferdeghini M, Lo Cascio V: Long-term quiescence of ectopic Cushing's syndrome caused by pulmonary neuroendocrine tumor (typical carcinoid) and tumorlets: spontaneous remission or therapeutic effect of bromocriptine? J Endocrinol Invest; 2006 Apr;29(4):358-62
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  • [Title] Long-term quiescence of ectopic Cushing's syndrome caused by pulmonary neuroendocrine tumor (typical carcinoid) and tumorlets: spontaneous remission or therapeutic effect of bromocriptine?
  • Medical treatment with bromocriptine and cyproheptadine led to a rapid and stabile normalization of adrenal function, so that after two months cyproheptadine was stopped and bromocriptine was tapered to a smaller dose.
  • An attempt to discontinue medical treatment, carried out 3 yr later, was followed by a quick increase of ACTH and cortisol levels, which were normalized by the resumption of the bromocriptine.
  • Adrenal function remained normal until 1994 when hypercortisolism relapsed despite the treatment.
  • Chest radiography and computed tomography (CT) scan detected a 6 mm nodule in the middle lobe of the lung which proved to be a neuroendocrine tumor, with immunohistochemical positivity for ACTH.
  • Nests of neuroendocrine cells (tumorlets) were also demonstrated in the surrounding lung tissue.
  • Although cyclical spontaneous Cushing's syndrome could not be excluded, there was strong evidence that medical treatment with bromocriptine might have played a key role in long-lasting remission.
  • To our knowledge, this is the second case described in literature of Cushing's syndrome caused by neuroendocrine lung tumor responsive to bromocriptine.
  • [MeSH-major] ACTH Syndrome, Ectopic / complications. ACTH Syndrome, Ectopic / drug therapy. Bromocriptine / therapeutic use. Carcinoid Tumor / complications. Carcinoid Tumor / drug therapy. Cushing Syndrome / etiology. Lung Neoplasms / complications. Neoplasm Regression, Spontaneous


14. Okada D, Kawamoto M, Koizumi K, Tanaka S, Fukuda Y: Immunohistochemical study of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma of the lung. Jpn J Thorac Cardiovasc Surg; 2003 Jul;51(7):272-6
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  • [Title] Immunohistochemical study of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma of the lung.
  • OBJECTIVES: In 1999, the World Health Organization categorized pulmonary large cell neuroendocrine carcinoma as a variant of large cell carcinoma.
  • However, an optimal treatment for large cell neuroendocrine carcinoma has not been established yet.
  • Recently, multimodality therapy combining both surgery and adjuvant chemotherapy has been reported as a useful treatment for large cell neuroendocrine carcinoma, but the effect of chemotherapy on it has not yet been fully investigated.
  • Thus, we evaluated immunohistochemical data of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma.
  • METHODS: We identified 10 large cell neuroendocrine carcinomas (1.2%) out of 850 primary lung cancers that had been surgically resected.
  • We examined the immunohistochemical staining of three drug-resistant proteins, namely, P-glycoprotein, metallothionein and glutathione S-transferase-pi to compare large cell neuroendocrine carcinoma with other histological types of lung cancer.
  • RESULTS: The mean tumor cell positivity rates for P-glycoprotein, metallothionein and glutathione S-transferase-pi in large cell neuroendocrine carcinoma were 0%, 2.4 +/- 3.6% and 35.0 +/- 37.5%, respectively.
  • These drug-resistant proteins showed similar expression pattern in both large cell neuroendocrine carcinoma and small cell carcinoma except glutathione S-transferase-pi.
  • CONCLUSION: Immunohistochemical expression of drug-resistant proteins in large cell neuroendocrine carcinoma was lower than that in adenocarcinoma and squamous cell carcinoma, and differences exist in drug-resistance between large cell neuroendocrine carcinoma and small cell carcinoma.
  • [MeSH-major] Carcinoma, Large Cell / pathology. Carcinoma, Neuroendocrine / pathology. Carcinoma, Non-Small-Cell Lung / pathology. Glutathione Transferase / biosynthesis. Isoenzymes / biosynthesis. Lung Neoplasms / pathology. Metallothionein / biosynthesis. P-Glycoprotein / biosynthesis
  • [MeSH-minor] Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Follow-Up Studies. Glutathione S-Transferase pi. Humans. Immunohistochemistry. Japan. Male. Middle Aged. Neoplasm Staging. Radiotherapy, Adjuvant. Surgical Procedures, Operative

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  • (PMID = 12892456.001).
  • [ISSN] 1344-4964
  • [Journal-full-title] The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai zasshi
  • [ISO-abbreviation] Jpn. J. Thorac. Cardiovasc. Surg.
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Isoenzymes; 0 / P-Glycoprotein; 9038-94-2 / Metallothionein; EC 2.5.1.18 / GSTP1 protein, human; EC 2.5.1.18 / Glutathione S-Transferase pi; EC 2.5.1.18 / Glutathione Transferase
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15. Erhan Y, Dikmen Y, Yucebilgin MS, Zekioglu O, Mgoyi L, Terek MC: Large cell neuroendocrine carcinoma of the uterine corpus metastatic to brain and lung: case report and review of the literature. Eur J Gynaecol Oncol; 2004;25(1):109-12
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  • [Title] Large cell neuroendocrine carcinoma of the uterine corpus metastatic to brain and lung: case report and review of the literature.
  • Neuroendocrine carcinoma of the uterine corpus is a rare aggressive tumor with a similar unfavorable outcome to that of the cervix.
  • The large cell type is considerably rarer than the small cell neuroendocrine carcinoma of the uterine corpus.
  • We report a case of a 52-year-old woman who presented with a large cell neuroendocrine tumor of the uterine corpus with very aggressive clinical behavior, cerebral and pulmonary metastases six and four months after initial diagnosis and adjuvant radiotherapy, respectively.
  • Despite successful surgical extirpation of the cerebral metastatic lesion she did not respond to chemotherapy and died four months after disease recurrence.
  • [MeSH-major] Brain Neoplasms / diagnosis. Carcinoma, Neuroendocrine / diagnosis. Lung Neoplasms / diagnosis. Uterine Neoplasms / diagnosis
  • [MeSH-minor] Diagnosis, Differential. Fatal Outcome. Female. Humans. Middle Aged. Neoplasm Recurrence, Local

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  • (PMID = 15053077.001).
  • [ISSN] 0392-2936
  • [Journal-full-title] European journal of gynaecological oncology
  • [ISO-abbreviation] Eur. J. Gynaecol. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Italy
  • [Number-of-references] 31
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16. Foroulis CN, Iliadis KH, Mauroudis PM, Kosmidis PA: Basaloid carcinoma, a rare primary lung neoplasm: report of a case and review of the literature. Lung Cancer; 2002 Mar;35(3):335-8
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  • [Title] Basaloid carcinoma, a rare primary lung neoplasm: report of a case and review of the literature.
  • Basaloid carcinoma of the lung is a rare primary neoplasm, first described in 1992.
  • Basaloid carcinoma is an aggressive subtype of Non small cell lung cancer, with poor 5-year survival, even in stage I and II resected tumors.
  • Differential diagnosis from small cell, Neuroendocrine large cell and poorly differentiated squamous cell carcinoma is difficult to be made.
  • We report a patient with lung basaloid carcinoma, initially diagnosed and treated as small cell carcinoma.
  • Thoracotomy and resection of the tumor following chemotherapy, established the correct diagnosis.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / diagnosis. Lung Neoplasms
  • [MeSH-minor] Diagnosis, Differential. Humans. Male. Middle Aged. Neoplasm Invasiveness. Pulmonary Disease, Chronic Obstructive / complications

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  • (PMID = 11844610.001).
  • [ISSN] 0169-5002
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Ireland
  • [Number-of-references] 9
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17. Bing Z, Adegboyega PA: Metastasis of small cell carcinoma of lung into an ovarian mucinous neoplasm: immunohistochemistry as a useful ancillary technique for diagnosis and classification of rare tumors. Appl Immunohistochem Mol Morphol; 2005 Mar;13(1):104-7
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  • [Title] Metastasis of small cell carcinoma of lung into an ovarian mucinous neoplasm: immunohistochemistry as a useful ancillary technique for diagnosis and classification of rare tumors.
  • The authors report the first case of ovarian mucinous adenocarcinoma with metastasis from a synchronous small cell neuroendocrine carcinoma of the lung.
  • She was found to have a large, complex cystic mass in the pelvis, and during the staging evaluation, a large, right pulmonary hilar mass was detected.
  • The patient received 3 cycles of chemotherapy with carboplatin and subsequently underwent a supracervical hysterectomy and bilateral salpingo-oophorectomy.
  • Microscopic examination disclosed a mucinous neoplasm with both mucinous cystadenoma and mucinous papillary adenocarcinoma components.
  • A microscopic focus of cells with "atypical" cytomorphologic features was detected within the mucinous neoplasm.
  • Immunohistochemistry showed that group of cells to be positive for thyroid transcription factor 1 and chromogranin, confirming them to be metastasis from the pulmonary small cell neuroendocrine carcinoma.

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  • (PMID = 15722802.001).
  • [ISSN] 1541-2016
  • [Journal-full-title] Applied immunohistochemistry & molecular morphology : AIMM
  • [ISO-abbreviation] Appl. Immunohistochem. Mol. Morphol.
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Chromogranins; 0 / Nuclear Proteins; 0 / Transcription Factors; 0 / thyroid nuclear factor 1; EC 1.11.1.- / Peroxidases
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18. Beasley MB, Thunnissen FB, Brambilla E, Hasleton P, Steele R, Hammar SP, Colby TV, Sheppard M, Shimosato Y, Koss MN, Falk R, Travis WD: Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol; 2000 Oct;31(10):1255-65
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  • [Title] Pulmonary atypical carcinoid: predictors of survival in 106 cases.
  • Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC).
  • Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC).
  • Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response.
  • We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC.
  • Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven.
  • [MeSH-major] Carcinoid Tumor / mortality. Lung Neoplasms / mortality

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  • (PMID = 11070119.001).
  • [ISSN] 0046-8177
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
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19. De Dosso S, Bajetta E, Procopio G, Cortinovis D, Buzzoni R, Catena L, Platania M, Verzoni E: Pulmonary carcinoid tumours: indolent but not benign. Oncology; 2007;73(3-4):162-8
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  • [Title] Pulmonary carcinoid tumours: indolent but not benign.
  • BACKGROUND: The aim of this retrospective study was to analyse the malignant behaviour of low-grade pulmonary neuroendocrine tumours (NETs) treated at our institution.
  • PATIENTS AND METHODS: We reviewed 48 consecutive patients with pulmonary NETs referred to our Medical Oncology Unit between 1998 and 2006, including 33 subjects with typical carcinoids (TCs) and 15 with atypical carcinoids (ACs).
  • Medical treatments used were somatostatin analogues, combined chemotherapy, within study protocols, 5-fluorouracil/dacarbazine/epiadriamycin (FDE), and oxaliplatin plus capecitabine (XELOX).
  • CONCLUSION: Cell type is the strongest determinant of prognosis, and the degree of malignancy increases from TCs to ACs.
  • Moreover, the prognosis of metastatic pulmonary carcinoids is not as good as expected.
  • Our analysis suggests that patients with advanced disease should receive first-line therapy with a somatostatin analogue, with chemotherapy regimens (FDE, XELOX) used in progressing cases.
  • [MeSH-major] Carcinoid Tumor / pathology. Lung Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Disease Progression. Disease-Free Survival. Female. Humans. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Recurrence, Local / diagnosis. Neoplasm Staging. Prognosis. Retrospective Studies. Survival Rate

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  • [Copyright] (c) 2008 S. Karger AG, Basel
  • (PMID = 18418008.001).
  • [ISSN] 1423-0232
  • [Journal-full-title] Oncology
  • [ISO-abbreviation] Oncology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
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20. Mikami Y, Nakajima M, Hashimoto H, Irei I, Matsushima T, Kawabata S, Manabe T: Primary pulmonary primitive neuroectodermal tumor (PNET). A case report. Pathol Res Pract; 2001;197(2):113-119; discussion 121-2
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  • [Title] Primary pulmonary primitive neuroectodermal tumor (PNET). A case report.
  • We describe a rare case of a primary primitive neuroectodermal tumor (PNET) in the lung of a 17-year-old girl.
  • Immunohistochemically, the tumor was positive for the MIC2 gene product, whereas AE1/AE3, CAM5.2, and a variety of neuroendocrine markers such as chromogranin A, synaptophysin, and ProGRP, were negative.
  • Three months after the lobectomy, recurrent tumors were noted in the mediastinum and right thoracic wall, and she died despite combined chemotherapy and radiation therapy.
  • This case indicates that the primary pulmonary PNET is a highly aggressive neoplasm occurring at a young age, and should prompt combined systemic chemotherapy, even though it is organ-confined.
  • [MeSH-major] Lung Neoplasms / pathology. Neuroectodermal Tumors, Primitive, Peripheral / pathology
  • [MeSH-minor] Adolescent. Carcinoma, Small Cell / diagnosis. Combined Modality Therapy. DNA Primers / chemistry. DNA, Neoplasm / analysis. Diagnosis, Differential. Fatal Outcome. Female. Humans. Karyotyping. Oncogene Proteins, Fusion / genetics. Proto-Oncogene Protein c-fli-1. RNA-Binding Protein EWS. Radiography, Thoracic. Reverse Transcriptase Polymerase Chain Reaction. Tomography, X-Ray Computed. Transcription Factors / genetics. Tumor Cells, Cultured

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  • (PMID = 11261815.001).
  • [ISSN] 0344-0338
  • [Journal-full-title] Pathology, research and practice
  • [ISO-abbreviation] Pathol. Res. Pract.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / DNA Primers; 0 / DNA, Neoplasm; 0 / EWS-FLI fusion protein; 0 / Oncogene Proteins, Fusion; 0 / Proto-Oncogene Protein c-fli-1; 0 / RNA-Binding Protein EWS; 0 / Transcription Factors
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21. Hage R, de la Rivière AB, Seldenrijk CA, van den Bosch JM: Update in pulmonary carcinoid tumors: a review article. Ann Surg Oncol; 2003 Jul;10(6):697-704
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  • [Title] Update in pulmonary carcinoid tumors: a review article.
  • Pulmonary carcinoid tumors are neuroendocrine malignant tumors that make up 1% to 2% of all lung tumors.
  • Carcinoids can be placed in a spectrum of neuroendocrine tumors, ranging from low-grade malignant TC to intermediate AC to high-grade large-cell neuroendocrine carcinoma and small-cell lung carcinoma.
  • Familial pulmonary carcinoids are rare.
  • The most common symptoms are hemoptysis, cough, recurrent pulmonary infection, fever, chest discomfort and chest pain, unilateral wheezing, and shortness of breath.
  • The treatment of choice is surgical resection, and prognosis is relatively good in TC, although it is worse in AC.
  • The role of radiotherapy and chemotherapy as part of multimodality treatment or palliation is still debated.
  • [MeSH-major] Carcinoid Tumor / pathology. Lung Neoplasms
  • [MeSH-minor] Biopsy. Bronchoscopy. Chemotherapy, Adjuvant. Combined Modality Therapy. Cough / etiology. Fever / etiology. Hemoptysis / etiology. Humans. Neoplasm Staging. Palliative Care. Prognosis. Radioimmunodetection. Radiotherapy, Adjuvant. Respiratory Sounds / etiology. Somatostatin

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  • (PMID = 12839856.001).
  • [ISSN] 1068-9265
  • [Journal-full-title] Annals of surgical oncology
  • [ISO-abbreviation] Ann. Surg. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 51110-01-1 / Somatostatin
  • [Number-of-references] 65
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22. Liptak JM, Kamstock DA, Dernell WS, Ehrhart EJ, Rizzo SA, Withrow SJ: Cranial mediastinal carcinomas in nine dogs. Vet Comp Oncol; 2008 Mar;6(1):19-30
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  • Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas.
  • All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively.
  • Adjunctive therapies included pre-operative radiation therapy (n=1) and postoperative chemotherapy (n=3).
  • Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery.
  • The overall median survival time was 243 days.
  • Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series.
  • [MeSH-minor] Animals. Carcinoma, Medullary / diagnosis. Carcinoma, Medullary / mortality. Carcinoma, Medullary / surgery. Carcinoma, Medullary / veterinary. Carcinoma, Neuroendocrine / diagnosis. Carcinoma, Neuroendocrine / mortality. Carcinoma, Neuroendocrine / surgery. Carcinoma, Neuroendocrine / veterinary. Dogs. Female. Male. Neoplasm Invasiveness. Neoplasm Recurrence, Local / veterinary. Prognosis. Survival Analysis. Thyroid Neoplasms / diagnosis. Thyroid Neoplasms / mortality. Thyroid Neoplasms / surgery. Thyroid Neoplasms / veterinary. Treatment Outcome

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  • (PMID = 19178660.001).
  • [ISSN] 1476-5829
  • [Journal-full-title] Veterinary and comparative oncology
  • [ISO-abbreviation] Vet Comp Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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23. Erelel M, Toker SA, Yakar F, Yakar AA, Yildiz R, Kaya ZB: Multifocal endobronchial carcinoid tumors: a rare case. J Bronchology Interv Pulmonol; 2010 Apr;17(2):158-61

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  • Computed tomography of the chest showed tubular densities in the bilateral lower lobes and a 15-mm soft-tissue mass in the right lower lobe without any enlargement in the mediastinal lymph nodes.
  • On positron emission tomography scan, there was no fluorodeoxyglucose uptake in any of these lesions.
  • The pathologic examination of biopsies showed neuroendocrine neoplasm and typical bronchial carcinoid tumor.
  • Although the only effective treatment for a bronchial carcinoid is complete surgical excision of the tumor, surgical resection was not performed in our patient because of multiple, bilateral, biopsy-proven endobronchial tumors.
  • Radiation and chemotherapy are generally reserved for symptomatic and metastatic disease, which was the treatment of choice for our patient.

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  • (PMID = 23168735.001).
  • [ISSN] 1944-6586
  • [Journal-full-title] Journal of bronchology & interventional pulmonology
  • [ISO-abbreviation] J Bronchology Interv Pulmonol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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24. Moore AM, Einhorn LH, Estes D, Govindan R, Axelson J, Vinson J, Breen TE, Yu M, Hanna NH: Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial. Lung Cancer; 2006 Apr;52(1):93-7
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  • BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC).
  • Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms.
  • Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function.
  • Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma.
  • Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen.
  • Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain.
  • Median time to progression (TTP) was 50 days (95% CI = 21-58 days).
  • CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Carcinoma, Small Cell / drug therapy. Drug Resistance, Neoplasm. Lung Neoplasms / drug therapy. Quinazolines / therapeutic use
  • [MeSH-minor] Aged. Female. Humans. Male. Maximum Tolerated Dose. Middle Aged. Neoplasm Recurrence, Local. Survival Rate. Treatment Outcome

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  • [CommentIn] Lung Cancer. 2006 Aug;53(2):255 [16762444.001]
  • (PMID = 16488055.001).
  • [ISSN] 0169-5002
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Quinazolines; S65743JHBS / gefitinib
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25. Hollaus PH, Wurnig PN, Pridun NS: [Bronchoplastic procedures for the resection of malignant bronchial neoplasms]. Chirurg; 2002 Nov;73(11):1115-22
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  • INTRODUCTION: Bronchoplastic procedures have become established in the treatment of bronchial malignancies.
  • PATIENTS AND METHODS: Bronchial reconstruction techniques (wedge resection, end-to-end-anastomosis, y-sleeve), comorbidity (cardiovascular, respiratory, pulmonary, neoadjuvant chemotherapy, alcoholism), postoperative complications (septic/aseptic, light/severe), histology, tnm-stage and postoperative follow up (days) were recorded prospectively.
  • In 11 patients (10.2%), an additional angioplasty of the pulmonary artery was performed.
  • CONCLUSION: Bronchoplastic procedures are a safe method for the treatment of bronchial malignancies, even in cases with high comorbidity, and should be performed whenever possible.
  • [MeSH-major] Adenocarcinoma / surgery. Bronchi / surgery. Bronchial Neoplasms / surgery. Carcinoma, Neuroendocrine / surgery. Carcinoma, Squamous Cell / surgery. Lung Neoplasms / surgery
  • [MeSH-minor] Adult. Aged. Anastomosis, Surgical. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoadjuvant Therapy. Neoplasm Staging. Pneumonectomy. Postoperative Complications / etiology. Postoperative Complications / mortality. Risk Factors. Survival Rate

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  • (PMID = 12430063.001).
  • [ISSN] 0009-4722
  • [Journal-full-title] Der Chirurg; Zeitschrift für alle Gebiete der operativen Medizen
  • [ISO-abbreviation] Chirurg
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Germany
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26. Doddoli C, Rollet G, Thomas P, Ghez O, Serée Y, Giudicelli R, Fuentes P: Is lung cancer surgery justified in patients with direct mediastinal invasion? Eur J Cardiothorac Surg; 2001 Aug;20(2):339-43
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Is lung cancer surgery justified in patients with direct mediastinal invasion?
  • OBJECTIVE: To assess the results of the surgical treatment of patients with stage IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4).
  • Three patients received a preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1).
  • The lung resection consisted of a pneumonectomy in 25 patients and a lobectomy in four.
  • The procedure was extended to one of the following structures: superior vena cava (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6).
  • Seventeen patients had a postoperative regimen including radiochemotherapy (n = 12), radiotherapy (n = 4), or chemotherapy (n = 1).
  • At completion of the study, 22 patients have died, two postoperatively and 10 from pulmonary causes without evidence of cancer.
  • CONCLUSIONS: Surgical management of T4 NSC lung cancer invading the mediastinum should be considered, in the absence of N2 disease, when a complete resection is achievable.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / pathology. Carcinoma, Non-Small-Cell Lung / surgery. Lung Neoplasms / pathology. Lung Neoplasms / surgery. Mediastinum / pathology. Pneumonectomy
  • [MeSH-minor] Adenocarcinoma / pathology. Adenocarcinoma / surgery. Adenocarcinoma / therapy. Adult. Aged. Carcinoma, Large Cell / pathology. Carcinoma, Large Cell / surgery. Carcinoma, Large Cell / therapy. Carcinoma, Neuroendocrine / pathology. Carcinoma, Neuroendocrine / surgery. Carcinoma, Neuroendocrine / therapy. Carcinoma, Squamous Cell / pathology. Carcinoma, Squamous Cell / surgery. Carcinoma, Squamous Cell / therapy. Cause of Death. Combined Modality Therapy. Female. Humans. Male. Middle Aged. Neoplasm Invasiveness. Prognosis. Retrospective Studies. Survival Analysis

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  • (PMID = 11463554.001).
  • [ISSN] 1010-7940
  • [Journal-full-title] European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
  • [ISO-abbreviation] Eur J Cardiothorac Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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27. Yamasaki T, Shimazaki H, Aida S, Tamai S, Tamaki K, Hiraide H, Mochizuki H, Matsubara O: Primary small cell (oat cell) carcinoma of the breast: report of a case and review of the literature. Pathol Int; 2000 Nov;50(11):914-8
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  • The patient was alive and well without disease 16 months after modified radical mastectomy and subsequent chemotherapy.
  • The tumor cells revealed morphologic similarity to oat cell carcinoma of the lung and immunohistochemical expression of neuroendocrine markers.
  • Review of nine previously reported cases and this case of primary small cell carcinoma of the breast has revealed that this type of tumor shows prominent vascular invasion, frequent lymph node metastasis, infrequent expression of estrogen receptor, and also very poor prognosis.
  • Immunohistochemical study for the c-kit proto-oncogene product, which has been reported to be a specific marker for pulmonary small cell carcinoma, demonstrated positive reactivity in approximately 80% of the tumor cells of this case, which is the first report according to our knowledge.
  • [MeSH-minor] Adult. Biomarkers, Tumor / analysis. Biopsy, Needle. Chemotherapy, Adjuvant. Cytoplasmic Granules / ultrastructure. Female. Humans. Immunohistochemistry. Mastectomy, Modified Radical. Neoplasm Proteins / analysis. Neurosecretory Systems / ultrastructure

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  • (PMID = 11107070.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] AUSTRALIA
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Neoplasm Proteins
  • [Number-of-references] 21
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28. Wang X, MacLennan GT, Lopez-Beltran A, Cheng L: Small cell carcinoma of the urinary bladder--histogenesis, genetics, diagnosis, biomarkers, treatment, and prognosis. Appl Immunohistochem Mol Morphol; 2007 Mar;15(1):8-18
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  • [Title] Small cell carcinoma of the urinary bladder--histogenesis, genetics, diagnosis, biomarkers, treatment, and prognosis.
  • Most patients present with advanced disease at the time of diagnosis.
  • Histologically, small cell carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart.
  • Coexistence with other types of carcinoma is common.
  • Histogenesis is uncertain; there are several competing theories, including origin from stem cells, from urothelial cells, and from neuroendocrine cells in normal or metaplastic urothelium.
  • Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies.
  • Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options.
  • Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies.

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  • (PMID = 17536302.001).
  • [ISSN] 1541-2016
  • [Journal-full-title] Applied immunohistochemistry & molecular morphology : AIMM
  • [ISO-abbreviation] Appl. Immunohistochem. Mol. Morphol.
  • [Language] ENG
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Neoplasm Proteins
  • [Number-of-references] 63
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29. Gilbert JA, Frederick LM, Pobst LJ, Ames MM: Hydrogen peroxide degradation and selective carbidopa-induced cytotoxicity against human tumor lines. Biochem Pharmacol; 2005 Apr 15;69(8):1159-66
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  • The carcinoid tumor, an uncommon neuroendocrine neoplasm, is associated with serotonin overproduction as is more common small cell lung carcinoma (SCLC).
  • alpha-Methyl-dopahydrazine (carbidopa), an inhibitor of the serotonin synthetic enzyme aromatic-L-amino acid decarboxylase, proved lethal to NCI-H727 lung carcinoid cells as well as NCI-H146 and NCI-H209 SCLC cells, but not to five other human tumor cell lines of differing origins [Gilbert JA, Frederick LM, Ames MM.
  • The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin.
  • Neither compound induced significant DNA damage in carbidopa-resistant NCI-H460 large cell lung carcinoma cells.
  • Furthermore, when carbidopa was incubated with a variety of tumor cell types, not only were decreased media H2O2 concentrations detected in the presence of cells, but cell lines least sensitive to carbidopa degraded exogenous H2O2 more rapidly than did sensitive cells.
  • Implicated in these studies, pyruvate degraded H2O2 in RPMI in a dose- and time-dependent manner and reversed carbidopa-induced cytotoxicity to carcinoid cells.
  • Extracellular pyruvate levels produced per h by resistant large cell lung carcinoma cells averaged four-fold that of sensitive carcinoid cells plated at equal density (24 h time course).
  • [MeSH-major] Aromatic Amino Acid Decarboxylase Inhibitors. Carbidopa / toxicity. Carcinoid Tumor / drug therapy. Carcinoma, Small Cell / drug therapy. Hydrogen Peroxide / metabolism. Lung Neoplasms / drug therapy
  • [MeSH-minor] Cell Survival / drug effects. Culture Media / chemistry. Culture Media / metabolism. Dose-Response Relationship, Drug. Humans. Kinetics. Oxidation-Reduction. Pyruvic Acid / metabolism. Pyruvic Acid / pharmacology. Tumor Cells, Cultured

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  • (PMID = 15794936.001).
  • [ISSN] 0006-2952
  • [Journal-full-title] Biochemical pharmacology
  • [ISO-abbreviation] Biochem. Pharmacol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aromatic Amino Acid Decarboxylase Inhibitors; 0 / Culture Media; 8558G7RUTR / Pyruvic Acid; BBX060AN9V / Hydrogen Peroxide; MNX7R8C5VO / Carbidopa
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