19 research outputs found
ANTILYMPHOCYTE ANTIBODIES (ALA) AND HUMAN IMMUNODEFICIENCY VIRUS (HIV) INDUCED INFECTION - CLINICAL AND PATHOGENIC STUDY
Tetraflagellochloris Mauritanica gen. et sp. nov. (Chlorophyceae), a New Flagellated Alga From the Mauritanian Desert: Morphology, Ultrastructure, and Phylogenetic Framing
Morphological, ultrastructural, and molecularsequence
data were used to assess the phylogenetic
position of a tetraflagellate green alga isolated from soil
samples of a saline dry basin near Fâderick, Mauritania.
This alga can grow as individual cells or form noncoenobial
colonies of up to 12 individuals. It has a
parietal chloroplast with an embedded pyrenoid covered
by a starch sheath and traversed by single parallel
thylakoids, and an eyespot located in a parietal position
opposite to the flagellar insertion. Lipid vacuoles are
present in the cytoplasm. Microspectroscopy indicated
the presence of chlorophylls a and b, with lutein as the
major carotenoid in the chloroplast, while the eyespot
spectrum has a shape typical of green-algal eyespots. The
cell has four flagella, two of them long and two
considerably shorter. Sequence data from the 18S rRNA
gene and ITS2 were obtained and compared with
published sequences for green algae. Results from
morphological and ultrastructural examinations and
sequence analysis support the placement of this alga in
the Chlorophyceae, as Tetraflagellochloris mauritanica
L. Barsanti et A. Barsanti, gen. et sp. nov
Novel targeting of phospho-cMET overcomes drug resistance and induces anti-tumor activity in multiple myeloma
PURPOSE:
The aim of the study was to verify the hypothesis that the cMet oncogene is implicated in chemio- and novel drug resistance in multiple myeloma.
EXPERIMENTAL DESIGN:
We have evaluated the expression levels of cMET/phospho-cMET (p-cMET) and the activity of the novel selective p-cMET inhibitor (SU11274) in multiple myeloma cells, either sensitive (RPMI-8226 and MM.1S) or resistant (R5 and MM.1R) to anti-multiple myeloma drugs, in primary plasma cells and in multiple myeloma xenograft models.
RESULTS:
We found that resistant R5 and MM.1R cells presented with higher cMET phosphorylation, thus leading to constitutive activation of cMET-dependent signaling pathways. R5 cells exhibited a higher susceptibility to the SU11274 inhibitory effects on viability, proliferation, chemotaxis, adhesion, and to its apoptogenic effects. SU11274 was able to revert drug resistance in R5 cells. R5 but not RPMI-8226 cells displayed cMET-dependent activation of mitogen-activated protein kinase pathway. The cMET and p-cMET expression was higher on plasma cells from patients with multiple myeloma at relapse or on drug resistance than on those from patients at diagnosis, complete/partial remission, or from patients with monoclonal gammopathy of unknown significance. Viability, chemotaxis, adhesion to fibronectin or paired bone marrow stromal cells of plasma cells from relapsed or resistant patients was markedly inhibited by SU11274. Importantly, SU11274 showed higher therapeutic activity in R5- than in RPMI-8226-induced plasmocytomas. In R5 tumors, it caused apoptosis and necrosis and reverted bortezomib resistance.
CONCLUSION:
Our findings suggest that the cMET pathway is constitutively activated in relapsed and resistant multiple myeloma where it may also be responsible for induction of drug resistance, thus providing the preclinical rationale for targeting cMET in patients with relapsed/refractory multiple myeloma
Recurrent adult-type fibrosarcoma of the frontal bone in a child
Primary, adult-type bone fibrosarcoma is an uncommon, malignant spindle-cell tumor of fibroblastic origin, rarely affecting children. Most frequently diagnosed among bone malignancies in the past, improved diagnostic techniques and further restrictive classification criteria have currently made the diagnosis of fibrosarcoma very unusual.We hereby report the case of a 7-year-old child with a right frontal swelling mass. A computed tomography scan showed an osteolytic lesion of the right frontal bone, involving the diploe and the outer table of the skull. An en bloc surgical excision, followed by a thorough immunohistological evaluation, led to the diagnosis of fibroblastic proliferation, with low cellularity and minimal atypias. The patient had four recurrences during the 4-year follow-up. With an increasing histological grade at recurrences, a diagnosis of adult-type fibrosarcoma was made.To the best of the authorsâ knowledge, this is the first reported case of an adult-type fibrosarcoma arising in the frontal bone of a child
Halting pro-survival autophagy by TGFÎČ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients
Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR).
The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9 %) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity