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Lucinda Aguirre-Cruz

Publications and source records attributed to Lucinda Aguirre-Cruz.

10 recordsLinked to original sources
PubMed2005

Clinical relevance of non-neuronal auto-antibodies in patients with anti-Hu or anti-Yo paraneoplastic diseases.

About half of the patients with paraneoplastic diseases develop an immune response against neuronal antigens expressed by both the tumor and the nervous system. In 31 patients with anti-Hu antibodies and 19 patients with anti-Yo antibodies, we searched for the presence of additional non-neuronal auto-antibodies and further studied whether the presence of such auto-antibodies was correlated with a specific oncological or neurological presentation. Positive antinuclear antibodies (ANA) were found at a titer of 1:40 or above in 48% patients with anti-Hu antibodies, and in 37% patients with anti-Yo antibodies. Anti-cytoplasmic antibodies were also detected in 42% patients with anti-Yo antibodies. No specific correlation between the presence of non-neuronal auto-antibodies and clinical characteristics of the patients could be identified. In particular, neither the type of underlying cancer, the overall survival, the tumor response to treatment, nor the neurological presentation were related to the serological status.

Aged↗
PubMed2004

CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas.

PURPOSE: The DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents, and its loss in cancer cells is associated with hypermethylation of the MGMT CpG island. Thus, methylation of MGMT has been correlated with the clinical response to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in primary gliomas. Here, we investigate whether the presence of MGMT methylation in gliomas is also a good predictor of response to another emergent alkylating agent, temozolomide. EXPERIMENTAL DESIGN: Using a methylation-specific PCR approach, we assessed the methylation status of the CpG island of MGMT in 92 glioma patients who received temozolomide as first-line chemotherapy or as treatment for relapses. RESULTS: Methylation of the MGMT promoter positively correlated with the clinical response in the glioma patients receiving temozolomide as first-line chemotherapy (n = 40). Eight of 12 patients with MGMT-methylated tumors (66.7%) had a partial or complete response, compared with 7 of 28 patients with unmethylated tumors (25.0%; P = 0.030). We also found a positive association between MGMT methylation and clinical response in those patients receiving BCNU (n = 35, P = 0.041) or procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (n = 17, P = 0.043) as first-line chemotherapy. Overall, if we analyze the clinical response of all of the first-line chemotherapy treatments with temozolomide, BCNU, and procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as a group in relation to the MGMT methylation status, MGMT hypermethylation was strongly associated with the presence of partial or complete clinical response (P < 0.001). Finally, the MGMT methylation status determined in the initial glioma tumor did not correlate with the clinical response to temozolomide when this drug was administered as treatment for relapses (P = 0.729). CONCLUSIONS: MGMT methylation predicts the clinical response of primary gliomas to first-line chemotherapy with the alkylating agent temozolomide. These results may open up possibilities for more customized treatments of human brain tumors.

Adult↗
PubMed2004

Distinct responses of xenografted gliomas to different alkylating agents are related to histology and genetic alterations.

A series of 12 human gliomas was established as xenografts in nude mice and used to evaluate the relationship between histology, genetic parameters, and response to alkylating agents. Eight were high-grade oligodendroglial tumors, and four were glioblastoma. They were characterized for their genetic alterations, including those considered as "early" alterations, namely loss of chromosome 1 +/- loss of chromosome 19q, TP53 mutation, and those considered as "late" alterations, namely loss of chromosome 10, loss of chromosome 9p, EGFR genomic amplification, PTEN mutation, CDKN2A homozygous deletion, and telomerase reactivation. Chemosensitivity of xenografts to four alkylating agents, temozolomide (42 mg/kg, days 1-5, p.o.), 1,3-bis(2-chloroethyl)-1-nitrosourea (5 mg/kg, day 1, i.p.), Ifosfamide (90 mg/kg, days 1-3, i.p.), and carboplatin (66 mg/kg, day 1, i.p.) was tested by administration of drugs to tumor-bearing mice. Although each tumor presented an individual response pattern, glioblastoma had a lower chemosensitivity than oligodendrogliomas, and temozolomide was the most effective drug. Deletion of 1p +/- 19q was associated with higher chemosensitivity, whereas late molecular alterations, particularly EGFR amplification, were associated with chemoresistance. These results suggest that the combined use of histology and molecular markers should eventually be helpful selecting the most appropriate agents for treatment of malignant oligodendrogliomas and astrocytomas.

Animals↗
PubMed2004

Analysis of the bHLH transcription factors Olig1 and Olig2 in brain tumors.

In the absence of specific markers, the histological diagnosis of oligodendroglial tumors is based on subjective qualitative criteria and remains controversial. Recently, two bHLH transcription factors involved in oligodendroglial specification, Olig1 and Olig2 have been proposed as potential markers of oligodendrogliomas. Expression of Olig1/2 was analyzed by in situ hybridization on 78 samples including 47 glial, 29 non-glial tumors, and two non-tumoral brain tissues. Both genes had a similar pattern of expression. Olig1 and Olig2 were expressed in 26/30 (87%) and 28/30 (93%) of oligodendroglial tumors respectively but in only 9% of glioblastomas (1/11). Olig genes were also expressed in the low-grade fibrillary astrocytomas (4/4) and anaplastic astrocytomas (2/2). No expression was found in non-glial tumors, except for one primary cerebral lymphoma. Double staining with PLP, NFH, GFAP showed that olig genes were expressed by mature, non-tumoral oligodendrocytes, but not by normal astrocytes or neurones. This study indicates that Olig1/2 expression clearly distinguishes pure Olig-negative glioblastomas from a wide spectrum of Olig-positive tumors including traditional oligodendrogliomas and oligoastrocytomas, glioblastomas with an oligodendroglial component (GBMO), and WHO grade 2 and 3 astrocytomas. Because Olig genes have a crucial role in oligodendroglial determination, our data could be of help in defining the real spectrum of oligodendroglial tumors.

Astrocytes↗
PubMed2004

Loss of 14q chromosome in oligodendroglial and astrocytic tumors.

Loss of chromosome 14q has been investigated in 142 gliomas. Loss of heterozygosity (LOH) at one or more microsatellite has been found in 8/30 grade II (27%) and 2/21 grade III (10%) oligodendrogliomas, 3/9 grade II (33%) and 5/15 grade III (33%) oligoastrocytomas, 0/9 grade II (0%) and 1/7 grade III (14%) astrocytomas, 11/51 glioblastomas (22%). Two minimal regions were identified on 14q21.2-14q24.3 (between D14S288 and D14S74) and 14q31.3-14q32.1 (between D14S74 and D14S65). Loss of 14q was not correlated to survival, histological grading and subtype or other genetic alterations, except for 1p deletions. Taken together, these data suggest that LOH14q is an early alteration involving 20% of glioma.

Astrocytoma↗
PubMed2004

Prognostic value of allelic losses and telomerase activity in meningiomas.

OBJECT: The goal of this study was to examine allelic losses and telomerase activity in meningiomas to determine whether they could be used to predict disease recurrence. METHODS: To identify predictive markers of recurrence, a cohort of high-grade (24 World Health Organization [WHO] Grade II and six WHO Grade III) and low-grade (21 WHO Grade I) meningiomas was investigated for losses of heterozygosity (LOHs) on chromosomes 1p, 9p, 10q, 14q, and 22q, a deletion of CDKN2A, and telomerase activity. Results of molecular analyses were compared with radiological and histological findings and progression-free survival (PFS). Losses of heterozygosity on chromosomes 22q, 1p, and 10q, as well as telomerase activity were related to the WHO histological grades of the lesions (p < 0.01, p < 10(-5), p < 10(-4), and p = 0.002, respectively). In the absence of an LOH on 22q, the other alterations were found infrequently. Overall, the number of molecular alterations was closely related to the histological grades of the lesions (p < 10(-6)). An LOH on 22q occurred much more frequently in convexity or falx (33 [87%] of 38 lesions) than in skull base or spinal meningiomas (four [31%] of 13 lesions) (p < 0.001). The histological grade; Simpson grade; an LOH on chromosome 1p, 9p, or 10q; and telomerase activity were correlated with a shorter PFS time (p < 10(-4), p = 0.02, p = 0.000365, p = 0.022, p = 0.00027, and p = 0.000512, respectively). CONCLUSIONS: On the basis of these data the authors suggest that LOH analysis and a telomerase activity assay could be useful to determine molecular predictors of outcome in patients with meningiomas.

Adult↗
PubMed2003

Oligodendrogliomas: an update on basic and clinical research.

Oligodendrogliomas have been the focus of considerable interest over the past decade, ever since they were recognized as chemosensitive tumors. They were once believed to represent less than 5% of gliomas, but by using expanded criteria, they may well represent up to one third. In fact, morphologic criteria are vague and highly subjective and the histologic diagnosis, therefore, remains highly controversial and unsatisfactory. New oligodendrocytic lineage markers, such as OLIG1/2 gene, will probably help to define the real spectrum of oligodendroglial tumors, which may include a wide variety of tumors with very different prognoses. Recently, genetic markers, and particularly loss of 1p and 19q chromosomes, have been shown to predict both prognosis and response to treatment. There is little doubt that these emerging techniques will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.

Animals↗
PubMed2003

Shared oligodendrocyte lineage gene expression in gliomas and oligodendrocyte progenitor cells.

OBJECT: Gliomas (astrocytic and oligodendroglial) are the most frequently occurring primary neoplasms in the central nervous system (CNS). Histological classification, which can be performed to distinguish astrocytomas from oligodendrogliomas, is essentially based on pathological features and has great prognostic and therapeutic value but lacks reproducibility. Specific markers of cell lineage, especially those f or oligodendrogliomas, are still lacking. The oligodendrocyte lineage (OLIG) genes, transcriptional factors of the basic helix-loop-helix family, have been recently identified in oligodendrocyte progenitor cells (OPCs) in the CNS of developing and adult rodents. Data from a few studies have shown in a small series of brain tumors that OLIG genes characterize oligodendrogliomas. To search for a differential expression of the OLIG genes in subgroups of brain tumors, the authors investigated OLIG1 and OLIG2 gene expression. METHODS: Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the authors analyzed a series of 89 tumors (71 astrocytic and oligodendroglial tumors, eight ependymomas, three medulloblastomas, four meningiomas, and three schwannomas) and normal human brain tissue samples. It was demonstrated that OLIG gene expression was largely limited to glial tumors, that is, astrocytomas and oligodendrogliomas. A very low level was detected in ependymomas, whereas other tumors lacked OLIG gene expression altogether. Surprisingly, OLIG1 and OLIG2 expressionwas not limited to oligodendroglial tumors, but was observed in astrocytic lesions as well, independent of tumor grade. Interestingly, these genes were expressed at the highest level in pilocytic astrocytomas according to semiquantitative RT-PCR results, which were confirmed on dot blot analysis. In situ hybridization showed that the OLIG2 gene was expressed by tumor cells in pilocytic astrocytomas as well as those in oligodendrogliomas. CONCLUSIONS: The OLIG genes are additional markers shared by all gliomas andOPCs. These markers may help to classify gliomas, to improve understanding of their histogenesis, and to identify new therapeutic targets.

Astrocytoma↗
PubMed2002

Analysis of loss of chromosome 10q, DMBT1 homozygous deletions, and PTEN mutations in oligodendrogliomas.

OBJECT: Chromosomal deletions of 10q and candidate genes such as PTEN and DMBT1 have been thoroughly investigated in glioblastomas but few data specifically address oligodendrogliomas. METHODS: In this study, 39 pure oligodendrogliomas were investigated for loss of heterozygosity (LOH) on 10q, PTEN mutations, and DMBT1 homozygous deletions. The LOH on 10q was found in 19 (48%) of 39 oligodendrogliomas and was closely related to anaplasia (p = 0.02), shorter time to progression (p = 0.0005), and poorer survival (p = 0.035). The DMBT1 homozygous deletions were found in 10 (26%) of 39 oligodendrogliomas but only one PTEN mutation was detected. The LOH on 10q is a strong predictor of survival and could be a valuable prognostic marker in oligodendrogliomas. CONCLUSIONS: Frequent inactivation of DMBT1 contrasting with rare mutations of PTEN may indicate that DMBT1 is preferentially involved in oligodendrogliomas. Nevertheless, the absence of a correlation with survival makes the role of DMBT1 in tumorigenesis still questionable and warrants further investigation.

Agglutinins↗