Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases.

Cvitkovic, Esteban; Bachouchi, Mounir; Boussen, Hamouda; Busson, P.; Rousselet, Germain; Mahjoubi, R.; Flores, P.; Tursz, Thomas; Armand, J.P.; Azli, N.

doi:10.1200/jco.1993.11.12.2434

Cited by 77 publications

(54 citation statements)

References 39 publications

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“…In the nude mouse study, metastasis was only observed in the brain, cervical lymph nodes, and lungs, a distribution that does not mimic the human disease. Specifically, metastasis to the brain is not a clinical characteristic of NPC, 32 was not detected in our model, and may be accounted for in the nude mouse model by focal trauma caused by passing the needle through the hard palate. Thus, we have developed an orthotopic xenograft model of invasive and metastatic NPC disease that closely mimics human disease well enough to assist in further identifying cellular characteristics that direct aggressively invasive and disseminated growth as well as identifying effective targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

An Orthotopic Model of Metastatic Nasopharyngeal Carcinoma and Its Application in Elucidating a Therapeutic Target That Inhibits Metastasis

et al. 2011

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To define and therapeutically target mechanisms that mediate nasopharyngeal carcinoma (NPC) metastasis, we have developed a unique orthotopic xenograft mouse model that accurately recapitulates the invasive and metastatic behavior of human disease. Based on clinical and laboratory evidence that the PI3K/Akt/mTOR axis is involved in aggressive NPC tumor behavior, we chose it as a therapeutic target to test the utility of our orthotopic system for evaluating the effectiveness of a targeted treatment for metastatic NPC. Demonstrated herein, we have shown that both the development and growth of metastatic lesions are markedly reduced by the mTOR inhibitor sirolimus. Thus, this orthotopic model provides a platform to study potential therapeutics for advanced NPC and demonstrates that targeting the PI3K/Akt/mTOR pathway is a promising intervention against disseminated disease.

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Section: Discussionmentioning

confidence: 99%

An Orthotopic Model of Metastatic Nasopharyngeal Carcinoma and Its Application in Elucidating a Therapeutic Target That Inhibits Metastasis

et al. 2011

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“…Although nasopharyngeal carcinoma is classified as a subtype of head and neck squamous cell carcinoma, its unique epidemiology, clinical characteristics, etiology, and histopathology warrant separate efforts for the study of its underlying molecular mechanisms of carcinogenesis (1). For example, nasopharyngeal carcinoma patients tend to present at a more advanced stage of disease because the primary anatomical site of tumor growth is located in a silent area, and they exhibit higher metastatic potential when compared with other head and neck squamous cell carcinoma (3)(4)(5). In addition, a strong association of EBV and nasopharyngeal carcinoma has been widely accepted (1,6).…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays

Sriuranpong

Mutirangura²,

Gillespie

et al. 2004

Clinical Cancer Research

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A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin ␤ 4 ) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/␤-catenin and transforming growth factor ␤ pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma.

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“…Neutrophilia is frequently seen in large cell lung cancer (2), although it has been reported in association with a variety of tumors (3-7), particularly in the presence of marrow involvement (8,9). The leukocytosis is usually modest, in the range of 12-30×10 3 / l, although levels as high as 100× 10 3 / l have been reported (10).…”

Section: Discussionmentioning

confidence: 99%

Leukemoid Reaction in Association with Bone Marrow Necrosis due to Metastatic Prostate Cancer

et al. 2005

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An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8×10 3 / l. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved. (Internal Medicine 44: 1093-1096, 2005)

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Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases.

Abstract: The PNS described could help in the diagnosis and follow-up of UCNT patients because they may be the first manifestation of the disease or may reappear with relapse. BMI is a frequent finding in patients with metastases and is unrelated to PNS.

Cited by 77 publications

References 39 publications

An Orthotopic Model of Metastatic Nasopharyngeal Carcinoma and Its Application in Elucidating a Therapeutic Target That Inhibits Metastasis

An Orthotopic Model of Metastatic Nasopharyngeal Carcinoma and Its Application in Elucidating a Therapeutic Target That Inhibits Metastasis

Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays

Leukemoid Reaction in Association with Bone Marrow Necrosis due to Metastatic Prostate Cancer

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