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  • Author: Mihaela Grigore x
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Open access

Mihaela Grigore, Sergiu Teleman, Didona Ungureanu and Alina Mares

Abstract

Cervical cancer is one of the leading cancers in women worldwide. The detection and diagnosis of cervical carcinoma and its precursor lesions, called cervical intraepithelial lesions (CIN), represents the main goal in order to decrease the morbidity and mortality of this disease. In the majority of cases CIN resolve spontaneously. Only a minor part of the lesions develop to high-grade lesions and eventually invasive cancer and it is important to detect those CIN with potential to progress to cervical cancer. For clinical management it is important to distinguish the cervical dysplasia with regression potential in order to avoid unnecessary treatments. Many potential biomarkers have been analyzed for the characterization of cervical cancer and pre-cancer. So far, detection of HPV has been the most promising clinical application. Several new markers have been evaluated intensively and might be used in some clinical settings, mainly p16, MCM5/CDC6 and HPV RNA, integration of HPV DNA into the host genome, chromosomal imbalances. In this article, representative examples of these markers are presented in the context of improved cervical disease detection and progression.

Open access

Ondine Lucaciu, Dan Gheban, Olga Soriţau, Mihaela Băciuţ, Radu Septimiu Câmpian and Grigore Băciuţ

Abstract

Objective: The aim of this research is to evaluate the value of the histological score based on a histological record compared to the histometry for monitoring cranial bone defect healing. Methods: We designed a case -control study with a control and a study group. For a number of 60 CD1 mice representing the study group, a bone defect in the cranial bone was surgically induced and grafted with bone grafts obtained by tissue engineering. Bone grafts were obtained using embryonic stem cells seeded on a scaffold obtained from the red deer antler, and osteogenic basal and complex medium was used as differentiation medium. For other 30 CD1 mice representing the control group, a bone defect in the cranial bone was induced and left to heal without grafts. The regeneration process was assessed after 2 and 4 months using the histological healing scoring system and histometry. Results: The healing score was statistically significantly correlated with the defect size obtained by means of histometry (p<0.001). The evaluation of the parameters comprised in the healing score shows that regeneration of the bone diastasis was the most advanced in the group sacrificed at 4 months after plasty, which employed embryonic stem cells, a complex osteogenic differentiation medium and deer antler as scaffold. Conclusion: histological method based on a histological score is a valuable quantification system of bone regeneration comparable to histometry. Clinical Relevance: This study proves that the presented histological score can help the clinician in the process of bone regeneration evaluation.

Open access

Georgiana Emilia Grigore, Iuliu C. Ivanov, Mihaela Zlei, Angela Dăscălescu, Roxana Popescu, Tudor Petreuș and Eugen Carasevici

Abstract

Traffic of tumor- and normal cells through the peripheral blood (PB) of patients with B-cell chronic lymphocytic leukemia (B-CLL) to the lymph nodes (LN) or spleen/ liver sites is governed by specific changes in surface and intracellular molecule expression. The study aims to investigate the potential association between different lymphocyte subsets, chemokine receptors or genetic alterations and specific clinical signs in a group of B-CLL patients. Forty-three patients were included in the study. The expression of CCR7, CXCR5, CXCR3, CCR4, CD3, CD4, CD8, CD27, CD28, CD45RA, CD25, CD127, CD38 was tested by multiparameter flow cytometry. Genetic alterations were determined by MLPA. We found increased frequency of CD38+ B-CLL cells directly correlated with the presence of LN>5cm. CXCR5 and CCR7 are homogenously expressed by monoclonal B-CLL cells. CCR4+ B-CLL cell frequency is found to be lower in the PB of patients presenting particular LN involvement. Heterogeneous and complex genetic alterations were found and only the presence of trisomy 12 associated with less frequent axillary LN involvement. We also report a significant increase in the frequency of total T cells and T cell subsets (effector- and central memory CD4+ T cells, regulatory T cells, follicular T helper cells, distinct functional CD8+ T cells) with the occurrence of specific clinical manifestations. Chemokine receptor expression on circulating CD4+ T cell subsets was augmented in connection to some specific LN locations. Consequently, clinical manifestations in B-CLL are linked to both, factors intrinsic to the monoclonal B cells, and external influences coming from the microenvironment.

Open access

Adela Cristina Lazar, Mihaela Hedesiu, Aranka Ilea, Grigore Baciut, Mariana Pacurar and Radu-Septimiu Campian

Abstract

Purpose: The present study aims radiological aspects of the occurrence of osteonecrosis of the jaw age groups both in receiving i.v bisphosphonates tratment Imaging assessment of bisphosphonates therapy-induced osteonecrosis of the jaw it is important to differentiate neoplastic invasion, osteomyelitis, osteoradionecrosis induced by radiation or bone related pathology of general diseases.

Material and method: We conducted a retrospective clinical study including 22 patients (8 men and 14 women) with various stages of osteonecrosis of the jaw.

Results: Radiological examinations using CBCT are required in all therapeutic approach of osteonecrosis of jaw cases providing accurate informations of position, dimension and the link with anatomical structures.Our study showed that the prevalence of osteonecrosis of mandibular growth is higher in women than in men and the risk of osteonecrosis of the jaw in appearance is depending on age factor witch occurs more often between age 52-59 and 73-80 years old.

Conclusion: The multitude of complications due to treatment with bisphosphonates bind to an early and specialized therapeutic approach. Radiological examinations is a first choice in the detection and early diagnosis of osteonecrosis of the jaw, patients requiring a permanent supervision by the physician and dentist.

Open access

Iuliu C. Ivanov, Daniela Jitam, Georgiana E. Grigore, Mihaela Zlei, Anca V. Ivanov, Silvia Dumitraş, Eugen Carasevici and Ingritli C. Miron

Abstract

Background. A high occurrence of translocation t(4;11)(q21;q23) was reported in infant acute lymphoblastic leukemia (ALL) leading to the fusion of the mixed lineage leukemia (MLL) gene on chromosome 11 and the AF4 gene on chromosome 4. More than 50 distinct MLL-AF4 types of fusion have been previously identified, none of those reported matching the peculiarities found in an infant ALL case to be reported below. Materials and methods. Molecular tests were performed for the detection of TEL-AML1, BCR-ABL(p190), E2A-PBX1, and MLL-AF4 in the peripheral blood sample of a 21 days new-born boy suspected of ALL. An unexpected MLL-AF4 fragment was identified, further purified, and later analyzed by sequencing. Flow cytometry analyses were carried out at diagnosis and relapse on a FACSCanto-II cytometer (Becton-Dickinson). Results. The patient was found to be positive for the MLL-AF4 transcript, with an uncommonly long-sized product and a previously undescribed sequence (in-frame fusion between exon 12 of MLL and exon 4 of the AF4 gene). The immunophenotypic analyses also showed a particular development: while at diagnosis a dominant malignant clone displaying a B lymphoid precursor phenotype was described, at relapse a malignant monocytoid population predominantly expanded. The presence of MLL-AF4 e12-e4 transcript was still manifest at relapse, without other transcript characteristic for myeloid lineage. Conclusions. To our knowledge, this is the first report of a MLL-AF4 rearrangement revealing this complex transcript with new breakpoints in MLL. Its early detection may predict an immunophenotypic switch and may assist the clinicians in designing optimized therapies.

Open access

Georgiana E. Grigore, Angela Dascalescu, Mihaela Zlei, Iuliu C. Ivanov, Catalin Danaila, Tudor Petreus and Eugen Carasevici

Abstract

Background/aim: T lymphocytes are important players of the immune response. B-CLL is characterized by several immune defects. Our study aims to characterize the distinct maturational and functional T/NK cell subsets within B-cell chronic lymphocytic leukemia disease Rai stages. Patients and methods: Peripheral blood mononuclear cells from 43 patients enrolled in the study (16 females and 27 males, aged 68±10, 8 Rai 0, 22 Rai 1/2 and 13 Rai 3/4) were analyzed by multiparameter flow cytometry. Distinct subsets within the CD4+ (naive, central memory, effector/peripheral memory, regulatory-Tregs, follicular-TFH, CXCR3+ and/or CCR4+), CD8+ (naive+memory, effector, senescent) and NK (CD57+ and/or CD94+) were identified and compared between disease Rai stages. Results: Total numbers of T lymphocytes increase with disease stage. Both CD4+ and CD8+ T cells are elevated in absolute counts. The majority of CD4+ T cells are antigen-experienced, with increased Tregs, TFH and CXCR3+ (Th1-associated profile) T cell counts. The CD8+ T cells expansion is due mostly to the senescent CD57+ subset. No significant difference within NK subsets was observed among different disease stages. Conclusions: B-CLL behaviour seems to be associated with increased numbers of TFH and Tregs. The therapeutic modulation of T cell response in B-CLL patients may play an important role in the disease behaviour and may be a key event compensating for the immunodeficiency occurring mostly in advanced stages of the disease.