cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro

We studied the effects of cis-retinoic acid (cisRA) on the clonogenic growth of samples of leukemic cells from 35 patients with acute nonlymphocytic leukemia (ANLL). We observed significant inhibition of leukemic colony growth in 17 samples by 10(-7) to 10(-6)M cisRA. However, we found that retinoid exposure resulted in striking stimulation of clonal growth in ten samples at the same drug concentrations. With the exception of cases with promyelocytic features, there was no morphologic or functional evidence that cisRA induced the leukemic blasts to differentiate. Both inhibition and stimulation were dose-dependent and observable at pharmacologically achievable levels of cisRA. Leukemic cells with monocytic features more frequently demonstrated a stimulatory response than did those without monocytic features. Depletion of T lymphocytes and monocytes did not alter the type of growth response. Assays for cellular retinoic acid- binding protein (CRABP) were performed on five samples (two with inhibitory growth responses, two with stimulatory responses, and one with no growth) and failed to reveal detectable levels of CRABP in any case. The addition of cisRA to liquid suspensions of leukemic cells produced no significant change in the number of viable cells. We conclude that the effects of cisRA on leukemic colony growth are not cytotoxic and not mediated by T lymphocytes, monocytes, or CRABP. More importantly, cisRA appears to enhance the growth of certain human leukemia cells in vitro. Taking into account the increasing use of retinoids in clinical trials for patients with leukemia, the latter findings may represent a significant cautionary note.     

Proton magnetic resonance spectroscopy in the brain: report of AAPM MR Task Group #9

AAPM Magnetic Resonance Task Group #9 on proton magnetic resonance spectroscopy (MRS) in the brain was formed to provide a reference document for acquiring and processing proton (1H) MRS acquired from brain tissue. MRS is becoming a common adjunct to magnetic resonance imaging (MRI), especially for the differential diagnosis of tumors in the brain. Even though MR imaging is an offshoot of MR spectroscopy, clinical medical physicists familiar with MRI may not be familiar with many of the common practical issues regarding MRS. Numerous research laboratories perform in vivo MRS on other magnetic nuclei, such as 31P, 13C, and 19F. However, most commercial MR scanners are generally only capable of spectroscopy using the signals from protons. Therefore this paper is of limited scope, giving an overview of technical issues that are important to clinical proton MRS, discussing some common clinical MRS problems, and suggesting how they might be resolved. Some fundamental issues covered in this paper are common to many forms of magnetic resonance spectroscopy and are written as an introduction for the reader to these methods. These topics include shimming, eddy currents, spatial localization, solvent saturation, and post-processing methods. The document also provides an extensive review of the literature to guide the practicing medical physicist to resources that may be useful for dealing with issues not covered in the current article.     

Leïomyosarcome de la prostate: Neoplasie rare

The prostatic leïomyosarcoma is a very uncommon tumor of the adult. It is often diagnosed to an advanced stage, because of the clinical and radiological non specificity. Its prognosis is very dark.The objective of our study is to illustrate the important role of the imagering, represented by the CT and especially the MRI in the balance of extension and the post-therapeutic follow-up of this tumor.We report a 49 years old patient's observation, allowed for unrests mictionnels evolving since 6 months in a context of change of the general state. To the clinical exam, the prostate was increased of volume and nodular. A radiological balance made of US, CT and abdomino-pelvic MRI has been achieved. It showed an heterogeneous prostate, infiltrating the grease of neighborhood and the ureteral meats, with important bilateral urétéro-hydronephrosis of uphill. One also noted the presence of suspected hepatic nodules. A trans-perineal prostatic biopsy has been achieved, concluded to a prostatic leïomyosarcoma. Because of the bad general state and the importance of the local extension and from afar of the prostatic tumor, a trans-ureteral resection has been achieved, associated to a chemotherapy. The evolving have been marked by the patient's death after his second cure of chemotherapy.The CT and especially the MRI had a primordial role in the balance of local extension and from afar of the prostatic léïomyosarcoma and the only means to affirm the diagnosis is the histology completed by an immuno-histochimical study. Their therapeutic handling is not codified at the present time and their prognosis remained very dark.     

Detection of cytarabine resistance in patients with acute myelogenous leukemia using flow cytometry

Cytarabine (Ara-C) is currently used in the treatment of adult acute myeloid leukemia (AML). To predict the results of induction chemotherapy, it could be useful to detect leukemic cells that are resistant to Ara-C in patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM), we have developed a cell resistance index to Ara-C (RI). The technique has been applied to 121 bone marrow (BM) samples from patients with de novo AML treated by a regimen containing Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete remission (CR), and 24 patients did not and were considered drug-resistant (DR). The BM cells collected at diagnosis were cultured for 48 hours and underwent BrdUrd/DNA analysis. Among 25 patients with no or very low proliferative activity (<3% of cells in S-phase), the proportion of DR patients (nine of 25) was significantly higher than in a second group of 96 patients with detectable proliferative activity (15 of 96) (P < .025). Within this second group, there was a first group of nine patients with high RI values, which included only DR patients; a second group of 63 patients with low RI values, which included 62 CR patients; and a third group of 24 patients with intermediate RI values, which included 19 CR and five DR patients. In view of this series, our results show that it is possible to detect a majority of DR patients treated by Ara-C.