Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By screening a human fetal brain cDNA expression library using a monoclonal anti-phosphotyrosine antibody, we have isolated a cDNA clone encoding a receptor type protein-tyrosine kinase belonging to the EPH family, NET (neuronally expressed EPH-related tyrosine kinase). NET shows 87% homology in nucleotide sequence and 99% homology in the deduced amino acid sequence to rat elk, suggesting that NET is the human homologue of elk. The NET gene is mapped to human chromosome 3q21-q23 by PCR screening of a human-rodent somatic cell hybrid panel and by fluorescence in situ hybridization. Examination of NET mRNA expression in several human tissues has shown that the NET gene is expressed preferentially in brain as a 5-kb transcript. Steady-state levels of NET mRNA in human brain are greater in the midterm fetus than in the adult. Lower levels of NET mRNA are found in fetal kidney and adult skeletal muscle. The expression pattern of NET mRNA thus differs from that of elk, suggesting that these two gene products may perform distinct roles in human and rat. NET transcripts are detected in human NTera-2 teratocarcinoma cells after retinoic acid-induced neuronal differentiation. Several human tumor cell lines derived from neuroectoderm including primitive neuroectodermal tumor, small cell lung carcinoma, and neuroblastoma also express NET transcripts. Since the NET mRNA expression in human brain is developmentally regulated and is induced during neuronal differentiation, NET potentially plays important roles in human neurogenesis.
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PMID:cDNA cloning, molecular characterization, and chromosomal localization of NET(EPHT2), a human EPH-related receptor protein-tyrosine kinase gene preferentially expressed in brain. 866 91

The effects of doxorubicin and radiation on apoptosis, p53 expression, and tumor growth in human tumor xenografts were investigated. Human ependymoblastoma (NNE), primitive neuroectodermal tumor (YKP), glioblastoma (KYG) and small cell lung carcinoma (GLS) that are all transplantable to nude mice were treated with doxorubicin (8 mg/kg) or radiation (1 Gy). The histological study was performed by using TUNEL and p53 staining. Cytotoxic effects of doxorubicin and radiation were compared with no-treatment group by the growth curves and apoptotic index of tumor to each treatment. In NNE with wild-type p53, doxorubicin induced growth delay of tumors (tumor volume doubling time; 13.7+/-3.3 days in control group vs 30.4+/-1.5 days in doxorubicin group), but no growth delay of tumors in KYG and GLS with mutant type p53. While radiation-induced apoptosis appeared most frequently at 6 h after irradiation, doxorubicin-induced apoptosis had a tendency to appear later. Furthermore, although the frequency of doxorubicin-induced apoptosis was lower than that of apoptosis by 1 Gy irradiation, apoptotic cells appeared for many hours after the treatment. Doxorubicin-induced apoptosis may be correlated with p53 phenotype because apoptosis was induced only in tumor with wild-type p53, but it appeared less frequently and later than radiation-induced apoptosis.
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PMID:Comparison of effects of doxorubicin and radiation on p53-dependent apoptosis in vivo. 1067 69

Two cases of primitive neuroectodermal tumor of the lung are reported. The first case is a 41-year-old man with a tumor in the left upper lung, and the second case is a 30-year-old woman with a tumor in the right lower lung. In both cases, the tumors originated in the lung but not in the chest wall. No distant metastasis was detected. In case 1, transcutaneous fine-needle biopsy (TCNB) revealed small round cell proliferation, although bronchoscopic examination showed no abnormal findings. Both the expression of Mic2 protein and t(11;22)(q24;q12) translocation were proved in the tumor cells. The tumor cells were positive for periodic acid-Schiff (PAS), neuron-specific enolase (NSE), and vimentin, but negative for Leu7, chromogranin A, and pro-gastrin-releasing peptide (ProGRP). In case 2, bronchoscopic examination showed only compressive change in right lower lobe bronchi. TCNB revealed small round tumor cells expressing Mic2 protein. The tumor cells were negative for leukocyte common antigen, S100 protein, pankeratin, chromogranin A, and desmin, but weakly positive for NSE and moderately positive for Ki-67 (MIB1). Both patients were successfully treated by the combination of surgical resection and chemotherapy, and are alive with no sign of recurrence for approximately 22 months in case 1 and 16 months in case 2.
Lung Cancer 2000 Jan
PMID:Primary primitive neuroectodermal tumor of the lung: report of two cases. 1067 84

Highly migratory neuroectodermal cells share a common embryonic origin with cells of the central nervous system (CNS). They include enteric, parasympathetic, sympathoadrenal, and sensory neurons of the peripheral nervous system, Schwann cells, melanocytes, endocrine cells, and cells forming connective tissue of the face and neck. Because of their common embryologic origin, these cells and the tumors that derive from them can share genetic and antigenic phenotypes with gliomas, tumors derived from CNS glia. We recently discovered that chlorotoxin (ClTx), a 4-kD peptide purified from Leiurus quinquestriatus scorpion, is a highly specific marker for glioma cells in biopsy tissues (Soroceanu et al. Cancer Res 58:4871-4879, 1998) that can target tumors in animal models. We report on the specificity of ClTx as a marker for tumors of neuroectodermal origin that include peripheral neuroectodermal tumors (PNET) and gliomas. Specifically, we histochemically stained frozen and paraffin tissue sections of human biopsy tissues from 262 patients with a synthetically manufactured and biologically active ClTx bearing an N-terminal biotin. The vast majority (74 of 79) of primary human brain tumors investigated showed abundant binding of ClTx with greater than 90% ClTx-positive cells in each section. By comparison, 32 biopsies of uninvolved brain used for comparison were largely ClTx-negative, with only a few isolated reactive astrocytes showing some ClTx binding. However, as with gliomas, the vast majority of PNETs examined showed specific ClTx binding (31 of 34). These include medulloblastomas (4 of 4), neuroblastomas (6 of 7), ganglioneuromas (4 of 4), melanomas (7 of 7), adrenal pheochromocytomas (5 of 6), primitive PNET (1), small cell lung carcinoma (2 of 3), and Ewing's sarcoma (2 of 2). Under identical staining conditions, normal tissues from brain, skin, kidney, and lung were consistently negative for ClTx. These results suggest that chlorotoxin is a reliable and specific histopathological marker for tumors of neuroectodermal origin and that chlorotoxin derivatives with cytolytic activity may have therapeutic potential for these cancers.
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PMID:Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. 1211 67

We report a tumor in an 80-year-old man that was difficult to distinguish from other tumors, i.e., small cell carcinoma of the lung, PNET/Ewing tumor, malignant lymphoma, or malignant melanoma (amelanotic), and which was finally identified as cutaneous neuroendocrine carcinoma using immunohistochemical and ultrastructural methods. Autopsy did not show any tumors in the lungs, excluding the possibility of small cell carcinoma of the lung. Immunohistochemistry tests gave negative results for LCA, UCHL-1, CD3, and CD20, thereby excluding malignant lymphoma, and the negative results for S-100 protein and HMB-45 ruled out malignant melanoma. The possibility of PNET/Ewing sarcoma was also excluded because of negativity for CD99. In addition, the ultramicrostructure showed intercellular junctional complexes and neuroendocrine granules, indicating that the tumor had characteristics of both epithelial and neuroendocrine tissues. We therefore diagnosed the primary carcinoma of the skin as cutaneous neuroendocrine carcinoma.
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PMID:Immunohistochemical and ultrastructural investigation on cutaneous neuroendocrine carcinoma: report of a case and review of the literature. 1699 28

Ewing's sarcoma/primitive neuroectodermal tumor (PNET) has been the subject of recent reports describing morphologic variants (adamantinoma-like, large cell, spindle cell, sclerosing, clear cell, and vascular-like) of the most classic form, as well as cases displaying unusual morphologic differentiation and atypical immunohistochemical features. We report a case of an uncommon lung tumor in a 20-year-old female, morphologically and molecularly consistent with an Ewing's sarcoma/PNET tumor with foci of squamous differentiation, and peculiar expression of vimentin, high-molecular-weight keratins, p63, synaptophysin, and chromogranin. This case raises a challenging differential diagnostic problem with therapeutic implications: Should the patient be treated following the protocols for Ewing's sarcoma/PNET tumors or as for lung carcinoma with neuroendocrine features? The patient we report here was treated with neoadjuvant chemotherapy for Ewing's sarcoma/PNET according to Euro Ewing 99 study protocol followed by surgery and has no evidence of disease 15 months after the initial diagnosis. This highlights the importance of achieving the correct diagnosis of these atypical tumors using all clinical, morphological, and ancillary methods available to allow for their correct and timely treatment.
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PMID:PNET with neuroendocrine differentiation of the lung: Report of an unusual entity. 2414 Oct 23

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.
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PMID:Emerging therapies for pancreas neuroendocrine cancers. 2584 79

This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning.
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PMID:Brain and spinal tumour. 2593 56

Primitive neuroectodermal tumors (PNETs) are highly malignant small round blue cell tumors of neuroectodermal origin belonging to either central nervous system, autonomic nervous system or peripheral Askin's or Ewing's group of neoplasms. The latter generally arise in soft tissues of trunk or axial skeleton in children and early adolescents. However in adults this entity is very uncommon. Of all peripheral entities, primary PNET of lungs without chest wall or pleural involvement in adults are extremely rare and have been scarcely reported in world literature as single case reports. We hereby report a series of three interesting cases of adult PNET of lung diagnosed and treated in our institute. The chief presenting complaints of these patients were of chest pain, cough and dyspnea. The cases were diagnosed on the basis of imaging and biopsy which confirmed these lesions to be of PNET histology, confirmed by immunopositivity for neuron specific enolase (NSE), synaptophysin, chromogranin, CD 99 and vimentin on immunohistochemistry (IHC). All three were deemed unresectable in view of infiltration of nearby vital organs and high chances of morbidity. They were treated with upfront chemotherapy followed by conformal radiotherapy (RT) to the residual disease to which they showed significant response both clinically and radiologically. Presently these patients are on regular follow-up for over 6 months without any evidence of progression of disease or distant metastasis.
Transl Lung Cancer Res 2016 Jun
PMID:Primitive neuroectodermal tumor of lungs in adults: a rare series of three cases treated with upfront chemo-radiation. 2741 16

Primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms of embryonal origin manifesting in children and adolescents, rarely seen in adults. Carcinoma lung with hemorrhagic metastasis to the brain is very common, but primary lung PNET with hemorrhagic brain metastasis is extremely uncommon. We hereby report a 29-year-old female diagnosed as PNET lung was treated with vincristine, adriamycin, and cyclophosphamide alternating with ifosfamide plus etoposide followed by radiotherapy (RT). After 9 months, she developed hemorrhagic brain metastasis from PNET lung confirmed from tissue immunohistology postcraniotomy. Received palliative whole brain RT followed by oral pazopanib resulting in significant improvement in performance status. A thorough review of literature reveals that our case may be the second case of primary lung PNET with hemorrhagic brain metastasis and also the first to be exhibited oral pazopanib resulting in a significant therapeutic effect to be reported in world literature till date.
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PMID:Primitive Neuroectodermal Tumor of Lung in Adult with Hemorrhagic Brain Metastasis: An Extremely Rare Case Scenario. 2846 46


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