3q27 Aberrations in a Childhood Ovary Teratoma With Associated Malignant Germ Cell Component

Cytogenetic Studies of childhood ovary tumors have been poorly described. in the present article, the cytogenetic findings of an ovarian teratoma with malignant germ cell (yolk-sac) component occurring in an 8-year-old female are detailed. GTG-banding showed a karyotype of 46,XX, t(3;20)(q27;q13.3) [4]/46,XX, del3q27 [3]/46,XX [30]. Previous Studies have demonstrated common sites of loss of heterozygosity at 3q27-q28 region in different types of cancer, suggesting the presence of tumor Suppressor genes within this region. Pediatr Blood Cancer 2009;52:398-401. (C) 2008 Wiley-Liss, Inc.

HLA-G polymorphism and transitional cell carcinoma of the bladder in a Brazilian population

The morphologic appearance and clinical behavior of the human urinary bladder papillary transitional cell carcinoma (TCC) probably result from a complex interaction between carcinogenic insults and host resistance during the patient`s life. While the main recognized risk factors are of environmental origin (e.g. smoking), relatively little information exists about the susceptibility to TCC development. The human leukocyte antigen G (HLA-G) molecule plays an important role in immune response regulation and has been implicated in the inhibition of the cytolytic function of natural killer and cytotoxic T cells. Several lines of evidence indicate that HLA-G polymorphisms influence the expression level and production of different HLA-G isoforms. The aim of this study was to explore a possible influence of the HLA-G polymorphism on the susceptibility to urinary bladder TCC development and progression in smokers and nonsmokers Brazilian subjects. The HLA-G locus was found to be associated with susceptibility to TCC development and progression. The G*0104 allelic group (specially the G*010404 allele) and the G*0103 allele were associated with a tobacco-dependent influence on TCC development. The G*0104 group was associated with progression to high-grade tumors, irrespective of smoking habit, while the G*0103 allele was associated to high-grade tumor only in smoking patients. Our results are an evidence that the HLA-G locus itself, or as part of an extended haplotype encompassing this chromosome region (particularly the HLA-A given the high linkage disequilibrium observed between them in this data series), may be associated with TCC susceptibility and tumor progression, suggesting a tobacco-dependent influence of these polymorphisms.

Water excitation MPRAGE: An alternative sequence for postcontrast imaging of the abdomen in noncooperative patients at 1.5 Tesla and 3.0 Tesla MRI

Purpose: To evaluate the diagnostic image quality of post-gadolinium water excitation-magnetization-prepared rapid gradient-echo (WE-MPRAGE) sequence in abdominal examinations of noncooperative patients at 1.5 Tesla (T) and 3.0T MRI. Materials and Methods: Eighty-nine consecutive patients (48 males and 41 females; mean age +/- standard deviation, 54.6 +/- 16.6 years) who had MRI examinations including postgadolinium WE-MPRAGE were included in the study. Of 89 patients, 33 underwent noncooperative protocol at 1.5T. 10 under-went noncooperative protocol at 3.0T, and 46 underwent cooperative protocol at 3.0T. Postgadolinium WE-MPRAGE, MPRAGE, and three-dimensional gradient-echo sequences of these three different groups were qualitatively evaluated for image quality, extent of artifacts, lesion conspicuity, and homogeneity of fat-attenuation by two reviewers retrospectively, independently, and blindly. The results were compared using Wilcoxon signed rank and Mann-Whitney U tests. Kappa statistics were used to measure the extent of agreement between the reviewers. Results: The average scores indicated that the images were diagnostic for WE-MPRAGE at 1.5T and 3.0T in noncooperative patients. WE-MPRAGE achieved homogenous fat-attenuation in 31/33 (94%) of noncooperative patients at 1.5T and 10/10 (100%) of noncooperative patients at 3.0T. WE-MPRAGE at 3.0T had better results for image quality, extent of artifacts, lesion conspicuity and homogeneity of fat-attenuation compared with WE-MPRAGE at 1.5T. in noncooperative patients (P = 0.0008, 0.0006, 0.0024, and 0.0042: respectively). Kappa statistics varied between 0.76 and 1.00, representing good to excellent agreement. Conclusion: WE-MPRAGE may be used as a T1-weighted postgadolinium fat-attenuated sequence in noncooperative patients, particularly at 3.0T MRI.

Ovarian recovery after stem cell transplantation

Autologous or allogeneic SCT with conventional conditioning (chemotherapy with or without irradiation) has emergedas an effective and potentially curative therapy in patients with hematologic malignancies and in other selected solid tumors; however, several patients experience significant early and delayed side effects, including long-term endocrine imbalance and infertility. In spite of several reproductive recovery and pregnancy reports published in the oncology literature, review of medical literature reveals a paucity of comparable information in the SCT field. We report here four cases of ovarian recovery in patients who received hormonal replacement therapy after diagnosis of primary ovarian failure due to high-dose chemotherapy and SCT.

Autologous stem cell transplantation for early type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is the result of the autoimmune response against pancreatic insulin producing cells. This autoimmune response begins months or even years before the first presentation of signs and symptoms of hyperglycemia and at the time of clinical diagnosis near 30% of -cell mass still remains. In daily clinical practice, the main therapeutic option for T1DM is multiple subcutaneous insulin injections that are shown to promote tight glucose control and reduce much of diabetic chronic complications, especially microvascular complications. Another important aspect related to long-term complications of diabetes is that patients with initially larger -cell mass suffer less microvascular complications and less hypoglycemic events than those patients with small -cell mass. In face of this, -cell preservation is another important target in the management of type 1 diabetes and its related complications. For many years, various immunomodulatory regimens were tested aiming at blocking autoimmunity against -cell mass and at promoting -cell preservation, mainly in secondary prevention trials. In this review, we summarize some of the most important studies involving -cell preservation by immunomodulation and discuss our preliminary data on autologous nonmyeloablative hematopoietic stem cell transplantation in newly-diagnosed T1DM.

High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia

In the present study, we analyzed AURKA and AURKB gene expression in 70 acute myeloid leukemia (AML) patients. There was no difference between leukemic samples and bone marrow mononuclear cells (BMMCs, n = 8) or CD34(+) progenitors (n = 10) from healthy donors. High white blood cells (WBC) counts were observed in the AURKA(+) and AURKB(+) groups, but no significant differences regarding age, gender, platelet counts or frequency of FLT3-ITD mutations. AURKA, but not AURKB, expression was independently associated with high WBC counts (OR: 3.15, 95% CI 1.07-9.24, p = 0.03). Moreover, the majority of cases that overexpressed AURKA and AURKB presented unfavorable cytogenetic abnormalities (p < 0.001). In conclusion, we described a significant association between overexpression of AURKA/B and cytogenetics findings in AML, which may be relevant to new therapeutic approaches, based on Aurora kinase inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

Abnormal cell-cycle expression of the proteins p27, mdm2 and cathepsin B in oral squamous-cell carcinoma infected with human papillomavirus

Since the role of human papillomavirus (HPV) infection in oral carcinogenesis is still unclear, the purpose of this study was to verify the association between the expression of p27, mdm2 and cathepsin B and by HPV-related oral lesions. Fifty-five oral biopsies were studied and HPV detection and typing (6/11, 16, 18, 31 and 33) were performed using polymerase chain reaction techniques. The distribution p27, mdm2 and cathepsin B was determined by immunohistochemistry. Twenty-one (38%) out of the 55 oral lesions tested positive for HPV, of which 6(33%) were HPV 6/11, 1 (5%) was HPV 16,14 (72%) were HPV 18 and none was HPV 33/31. Among the 55 biopsies, immunopostivity for p27, mdm2 and cathepsin B was observed in 17 (30.9%), 37 (67.2%) and 37 (67.2%), respectively. Among 21 HPV-positive oral lesions, immunopostivity of mdm2, p27 and cathepsin B was found, respectively, in 6 (33%) out of 18 benign lesions (BL), 4(22%) out of 18 potential malignant epithelial lesions (PMEL) and 11(57.9%) out of 19 malignant lesions (ML). High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B. (C) 2009 Elsevier GmbH. All rights reserved.

Kallmann syndrome and mirror movements: White matter quantitative evaluation with magnetic resonance imaging

Kallmann syndrome (KS), characterized by the association of hypogonadotropic hypogonadism and anosmia, may present many other phenotypic abnormalities, including neurologic features as involuntary movements, called mirror movements (MM). MM etiology probably involves a complex mechanism comprising corticospinal tract abnormal development associated with deficient contralateral motor cortex inhibitory system. In this study, in order to address previous hypotheses concerning MM etiology, we identified and quantified white matter (WM) alterations in 21 KS patients, comparing subjects with and without MM and 16 control subjects, using magnetization transfer ratio (MTR) and T2 relaxometry (R2). Magnetization transfer and 12 double-echo images were acquired in a 1.5 T system. MTR and R2 were calculated pixel by pixel to initially create individual maps, and then, group average maps, co-registered with MNI305 stereotaxic coordinate system. After analysis of selected regions of interest, we demonstrated areas with higher 12 relaxation time and lower MTR values in KS patients, with and without MM, differently involving corticospinal tract projection, frontal lobes and corpus callosum. Higher MTR was observed only in pyramidal decussation when compared in both groups of patients with controls. In conclusion, we demonstrated that patients with KS have altered WM areas, presenting in a different manner in patients with and without MM. These data suggest axonal loss or disorganization involving abnormal pyramidal tracts and other associative/connective areas, relating to the presence or absence of MM. We also found a different pattern of alteration in pyramidal decussation, which can represent the primary area of neuronal disarrangement. (C) 2010 Elsevier B.V. All rights reserved.

BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Oral squamous Cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, all important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also it significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence oil BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC. but not in benign oral lesions.