(1/194) Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients.
18-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has previously been used successfully to image primary and metastatic breast cancer. In this pilot study, 19 breast cancer patients with symptoms/signs referrable to the brachial plexus were evaluated with 18FDG-PET. In 11 cases computerized tomography (CT) scanning was also performed. Of the 19 patients referred for PET study, 14 had abnormal uptake of 18FDG in the region of the symptomatic plexus. Four patients had normal PET studies and one had increased FDG uptake in the chest wall that accounted for her axillary pain. CT scans were performed in 9 of the 14 patients who had positive brachial plexus PET studies; six of these were either normal or showed no clear evidence of recurrent disease, while three CTs demonstrated clear brachial plexus involvement. Of two of the four patients with normal PET studies, one has had complete resolution of symptoms untreated while the other was found to have cervical disc herniation on magnetic resonance imaging (MRI) scan. The remaining two patients almost certainly had radiation-induced plexopathy and had normal CT, MRI and PET study. These data suggest that 18FDG-PET scanning is a useful tool in evaluation of patients with suspected metastatic plexopathy, particularly if other imaging studies are normal. It may also be useful in distinguishing between radiation-induced and metastatic plexopathy. (+info)
(2/194) TaqMan PCR-based gene dosage assay for predictive testing in individuals from a cancer family with INK4 locus haploinsufficiency.
BACKGROUND: A genetic syndrome of cutaneous malignant melanoma and nervous system tumors recently has been characterized and shown to be linked to the INK4 locus in the 9p21 region. Hemizygosity at adjacent physically mapped microsatellite markers indicated deletion of p16, p19, and p15 clustered tumor suppressors. Because individuals from this family could benefit from predictive testing in terms of cancer prevention, we developed a direct test without need to analyze parental DNAs to comply with the rules of individual consent and secrecy. METHODS: We developed an assay using TaqManTM real-time quantitative PCR, with p15 as the test sequence and albumin (ALB) as the reference gene. The normalized ratio of p15/ALB is expected to yield a value of approximately 1 in individuals without the deletion, whereas a ratio of approximately 0.5, indicating p15 haploinsufficiency, is expected in predisposed individuals. RESULTS: All patients harboring the previously defined at-risk haplotype were correctly identified using this approach. In six individuals with deletions, the p15/ALB ratios were 0.472-0.556 (SD, 0.013-0.078). In the five individuals without deletions, the ratios were 0.919-1.019 (SD, 0.006-0.075). CONCLUSIONS: This is the first report of a high-throughput, automatable gene dosage assay successfully applied to the identification of a germ-line deletion. This approach, not limited by marker informativeness or the need for harvesting live cells, can be applied to any condition with haploinsufficiency and extended to the characterization of most abnormalities of the ploidy. (+info)
(3/194) Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited-disease small-cell lung cancer: prolonged intrathoracic tumor control and high central nervous system relapse rate. Groupe d'Oncologie-Pneumologie Clinique de l'Universite Catholique de Louvain, Brussels and Liege, Belgium.
BACKGROUND: The role of chemotherapy dose-intensification in small-cell lung cancer (SCLC) remains unclear. This phase I-II study evaluates feasibility and outcome of combination chemotherapy at moderately elevated doses with concomitant thoracic radiotherapy in limited-disease SCLC. PATIENTS AND METHODS: Moderately elevated doses of ifosfamide-epirubicin (cycles 1 and 3) and of carboplatin-etoposide (cycles 2 and 4) were given with G-CSF and peripheral blood stem-cell (PBSC) support. Thoracic radiotherapy (40 Gy) was given once daily during the first five days of each cycle. RESULTS: Overall toxicity was acceptable; most common side-effects were myelosuppression and asthenia. All 35 eligible patients responded (23 CR, 12 PR). Median time to progression was 15 months: median overall survival was 24.6 months. Only 6 of 25 relapsing patients (24%) presented with a locoregional recurrence while 12 of 25 (48%) relapsed in the central nervous system (CNS). CONCLUSIONS: This regimen is a feasible dose-intensification with an acceptable toxicity profile. Its efficacy was demonstrated by a 100% response rate, an excellent local tumor control rate and a median survival of 24.6 months. In the absence of PCI, CNS relapse is a major problem if adequate local control is achieved. (+info)
(4/194) Site-specific epithelial-mesenchymal interactions in digestive neuroendocrine tumors. An experimental in vivo and in vitro study.
Little is known about the functional interactions between digestive neuroendocrine tumor cells and their stromal microenvironment. The focus of our study is whether mesenchymal cells modulate peptide expression, cell proliferation, and invasiveness in digestive neuroendocrine tumor cells. We designed an experimental in vivo and in vitro study using the mouse enteroendocrine cell line STC-1. In vivo, STC-1 cells were injected subcutaneously in 18 immunosuppressed newborn rats. At day 21, all animals presented poorly differentiated neuroendocrine tumors with lung metastases. Subcutaneous tumors were usually limited by a capsule containing basement membrane components and myofibroblasts that presented a low mitotic index. Lung tumors were devoid of capsule and poor in myofibroblasts, and their mitotic index was high. The profile of peptide expression in STC-1 tumors was different from that of cultured STC-1 cells. In vitro, STC-1 cells were cultured with fibroblasts of different origins, including dermis, lung, digestive tract, and liver. Based on their origin, myofibroblasts differentially modulated hormone synthesis, proliferation, spreading, and adhesion of STC-1 cells. In conclusion, our results show that site-specific functional interactions between mesenchymal and neuroendocrine cells may contribute to modulating the behavior of digestive neuroendocrine tumors, depending on their growth site. (+info)
(5/194) Morphologic characterization of spontaneous nervous system tumors in mice and rats.
Spontaneous rodent nervous system tumors, in comparison to those of man, are less well differentiated. Among the central nervous system (CNS) tumors, the "embryonic" forms (medulloblastoma, pineoblastoma) occur both in rodents and humans, whereas the human "adult" forms (gliomas, ependymomas, meningiomas) have fewer counterparts in rodents. In general, the incidence of spontaneous CNS tumors is higher in rats (>1%) than in mice (>0.001%). A characteristic rat CNS tumor is the granular cell tumor. Usually it is associated with the meninges, and most meningeal tumors in rats seem to be totally or at least partly composed of granular cells, which have eosinophilic granular cytoplasm, are periodic acid-Schiff reaction (PAS)-positive, and contain lysosomes. Such tumors are frequently found on the cerebellar surface or at the brain basis. Rat astrocytomas are diffuse, frequently multifocal, and they invade perivascular spaces and meninges. The neoplastic cells with round to oval nuclei and indistinct cytoplasm grow around preexisting neurons, producing satellitosis. In large tumors, there are necrotic areas surrounded by palisading cells. Extensive damage of brain tissue is associated with the presence of scavenger cells that react positively with histiocytic/macrophage markers. The neoplastic astrocytes do not stain positively for glial fibrillary acidic protein; they probably represent an immature phenotype. In contrast to neoplastic oligodendroglia, they bind the lectin RCA-1. Astrocytomas are frequently located in the brain stem, especially the basal ganglia. Rat oligodendroglial tumors are well circumscribed and frequently grow in the walls of brain ventricles. Their cells have water-clear cytoplasm and round, dark-staining nuclei. Atypical vascular endothelial proliferation occurs, especially at the tumor periphery. Occasionally in the oligodendrogliomas, primitive glial elements with large nuclei occur in the form of cell groups that form rows and circles. Primitive neuroectodermal tumors of rats, such as pineal tumors or medulloblastomas, appear to have features similar to those found in man. In mice, the meningeal tumors are mostly devoid of granular cells and the astrocytomas are similar to those occurring in rats, whereas spontaneous oligodendrogliomas are observed extremely rarely. Tumorlike lesions, such as lipomatous hamartomas or epidermoid cysts, are occasionally encountered in the mouse CNS. It is suggested that we classify rodent CNS lesions as "low grade" and "high grade" rather than as "benign" and "malignant." The size of CNS tumors is generally related to their malignancy. Tumors of the peripheral nervous system are schwannomas and neurofibromas or neurofibrosarcomas consisting of Schwann cells, fibroblasts, and perineural cells. Well-differentiated schwannomas are characterized by S-100 positivity and the presence of basement membrane. They show either Antoni A pattern with fusiform palisading cells or Antoni B pattern, which is sparsely cellular and has a clear matrix. The rat develops specific forms of schwannomas in the areas of the submandibular salivary gland, the external ear, the orbit, and the endocardium. Spontaneous ganglioneuromas occur in the rat adrenal medulla or thyroid gland. Compared to experimentally induced neoplasms, the spontaneous tumors of the rodent nervous system are poor and impractical models of human disease, although they may serve as general indicators of the carcinogenic potential of tested chemicals. (+info)
(6/194) Evaluation of ENU-induced gliomas in rats: nomenclature, immunochemistry, and malignancy.
Rats developed mixed gliomas, oligodendrogliomas, and a few astrocytomas in response to transplacental ethylnitrosourea. The neoplastic cell composition of mixed gliomas must be defined; this study required a 20-80% admixture of neoplastic astrocytes and oligodendroglia for the diagnosis of mixed glioma. A battery of immunoantibodies, including Leu-7, S-100, and vimentin, were helpful in classifying rat gliomas, and the histologic features of each tumor type are described. Other brain tumor characteristics that may decide the outcome of carcinogenicity studies include incidence, multiplicity, latency, fatality, size, and malignancy. The size of tumors was determined by measuring their 3-dimensional volumes. Brain tumor volume was found to be highly correlated with malignancy and fatality. Systematic evaluation of the malignancy of brain tumors is an important but often overlooked adjunct method of measuring the effectiveness of a carcinogen. A system to estimate malignancy, one that grades 9 tumor characteristics and weights, each according to clinical outcome, was developed. It was found that mixed gliomas grew larger, had a shorter latency, and were significantly more malignant than were other gliomas. (+info)
(7/194) Tumors of the nervous system in carcinogenic hazard identification.
In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents and mixtures for which there is sufficient evidence of carcinogenicity in experimental animals, usually rats and mice, as if they presented a carcinogenic risk to humans. Prediction of cancer sites in humans from bioassay data in rodents is much less certain, however, regardless of organ or tissue. For tumors of the nervous system, there is practically no basis for judging the validity of such predictions, as only ionizing radiation is known to cause tumors of the central nervous system (CNS) in humans. Brain tumors are relatively uncommon findings in bioassays and are rare in untreated rodents, even in rats, which appear to be the most susceptible species. However, CNS tumors have been readily induced in rodents by systemic exposures to some chemicals, notably N-nitrosoalkylureas and other alkylating agents and certain alkyl hydrazine derivatives. CNS tumors in rodents have played a significant role in carcinogenic hazard evaluations of several other chemicals, including acrylonitrile, ethylene oxide, and acrylamide, and have been implicated as part of the tumor spectrum induced by vinyl chloride and certain inorganic lead compounds. In some of these evaluations, it is not certain that all tumors diagnosed as primary brain tumors were correctly identified. Diagnostic difficulties have been presented by undifferentiated small-cell tumors that may invade the brain, including carcinomas of the nasal cavity and undifferentiated schwannomas arising in cranial nerve ganglia, and by the difficulty of reliably distinguishing between focal reactive gliosis and early glial neoplasms. The most striking experimental finding regarding the induction by chemicals of tumors of the nervous system is the dramatically greater susceptibility of the fetal and neonatal nervous system to some carcinogens, as compared with the susceptibility of the nervous system in adults of the same species. (+info)
(8/194) Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene.
High-frequent microsatellite instability (MSI-H) was detected in two of the 80 gliomas examined, whlie the other 78 gliomas showed microsatellite stable (MSS) phenotype. Both of the two MSI-H tumors were glioblastomas which developed in teenage patients. One of the patient was diagnosed as having Turcot's syndrome and had a germline mutation in the hMLH1 gene. Loss of expression due to promoter methylation was selectively observed in the wild type allele of the hMLH1 gene in the tumor of this patient. The other patient had neither a family history nor a past personal history of malignancy. Although no mutation in the mismatch repair genes was detected in the tumor of this patient, the level of expression of the hMLH1 gene was markedly decreased and the promoter sequence of the gene was highly methylated. In the tumor of this patient, the PTEN1 gene, one of the genes carrying microsatellite sequences in their coding regions, was altered by a slippage mutation within five adenine repeat sequences. These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI. (+info)