No abstract available

[en] 3-Hydroxypropionitrile was subjected to a base-catalyzed exchange reaction in D₂O which provided 2,2-dideuterio-3-deuteroxypropionitrile (DOCH₂CD₂CN) in 70% yield. Reduction of the nitrile with LiAID₄ gave 3-amino-2,2,3,3-tetradeuteriopropan-1-ol (HOCH₂CD₂CD₂NH₂) in a crude yield of 71%. Reaction of this intermediate with N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl₂P(O)N(CH₂CH₂Cl)₂] followed by the combination of those chromatography fractions which contained only pure material gave cyclophosphamide-4,4,5,5-d₄ as a white oil in 13% yield. A portion of this oil was converted to the monohydrate by the addition of water (1.1 equivalents) and crystallization from ether/petroleum ether (62% yield). For the hydrate, MS analyses gave an average mole percent enrichment (with average deviation over 5 determinations) of 89.1 ± 0.5% d₄. (author)

[en] A facile synthesis of the title compounds is described. The key intermediate in the synthesis, 6-demethyl-7,7-(ethylenedioxy)-6-(phenylselenenyl)mitosane (4) was synthesized in five steps from mitomycin A. Treatment of 4 with [¹⁴C]methyl iodide in the presence of K₂CO₃ afforded the [¹⁴C]-labelled mitosane (5). The removal of the phenylselenenyl group of 5 and subsequent treatment of the resultant mitosane with ammonia led to the desired [¹⁴C]mitomycin C (MMC) with specific activity of 50 mCi/mmol. Similarly, [³H]-labelled MMC with highly specific activity of 78.4 Ci/mmol was obtained. (author)

[en] We study the influence of cyclophosphamide, a chemotherapeutic drug used in neoplastic treatments, on the biodistribution, in mouse, of some ^99mTc-labelled compounds used to get scintigraphic images. The cyclophosphamide was administered intravenously in female BALB/cJ mouse, in two distinct doses with an interval of 48 hours. Then, the radiopharmaceutical (150 k Hq) was administered by the same via one hour later. These animals were sacrificed, their organs were isolated and the activity was counted in a well counter. The percentage of activity in the organs was calculated by four methods: dividing the activity in each organ by the sum of activities in all organs, dividing the activity in each organ by the total activity injected in animal, dividing the result obtained in method by the mass of the specific organ. The results were compared with a set of animals not treated with the chemo therapeutical (control). (author). 87 refs., 5 figs., 39 tabs

[en] Twenty patients with radiation sickness was administered 150 mg of Miradol daily, and the effects were observed in all of them. 13 patients showed significant effects in 3 days after the administration. Patients with chemotherapy or concurrent diseases showed poor effects and had a tendency to delay the onset of the effects. (Nishio, M.)

No abstract available

[en] In cancer cells, anticancer reagents often trigger nuclear accumulation of YB-1, which participates in the progression of cancer malignancy. YB-1 has a non-canonical nuclear localization signal (YB-NLS). Here we found that four nucleocytoplasmic-shuttling RNA-binding proteins and p53 interact specifically with the YB-NLS and co-accumulate with YB-1 in the nucleus of actinomycin D-treated cells. To elucidate the roles of these YB-NLS-binding proteins, we performed a dominant-negative experiment in which a large excess of YB-NLS interacts with the YB-NLS-binding proteins, and showed inhibitory effects on actinomycin D-induced nuclear transport of endogenous YB-1 and subsequent MDR1 gene expression. Furthermore, the YB-NLS-expressing cells were also found to show increased drug sensitivity. Our results suggest that these YB-NLS-associating proteins are key factors for nuclear translocation/accumulation of YB-1 in cancer cells. - Highlights: • Four nucleocytoplasmic-shuttling proteins and p53 associate with YB-NLS. • They showed nuclear co-accumulation with YB-1 in actinomycin D-treated cells. • Overexpression of YB-NLS was carried out to take YB-NLS-binding proteins from YB-1. • YB-NLS inhibited actinomycin D-induced nuclear localization of endogenous YB-1. • YB-NLS suppressed actinomycin D-induced expression of MDR1.

[en] Electrochemotherapy (ECT), a medical treatment widely used in human patients for tumor treatment, increases bleomycin toxicity by 1000 fold in the treated area with an objective response rate of around 80%. Despite its high response rate, there are still 20% of cases in which the patients are not responding. This could be ascribed to the fact that bleomycin, when administered systemically, is not reaching the whole tumor mass properly because of the characteristics of tumor vascularization, in which case local administration could cover areas that are unreachable by systemic administration. We propose combined bleomycin administration, both systemic and local, using companion animals as models. We selected 22 canine patients which failed to achieve a complete response after an ECT treatment session. Eleven underwent another standard ECT session (control group), while 11 received a combined local and systemic administration of bleomycin in the second treatment session. According to the WHO criteria, the response rates in the combined administration group were: complete response (CR) 54% (6), partial response (PR) 36% (4), stable disease (SD) 10% (1). In the control group, these were: CR 0% (0), PR 19% (2), SD 63% (7), progressive disease (PD) 18% (2). In the combined group 91% objective responses (CR+PR) were obtained. In the control group 19% objective responses were obtained. The difference in the response rate between the treatment groups was significant (p < 0.01). Combined local and systemic bleomycin administration was effective in previously to ECT non responding canine patients. The results indicate that this approach could be useful and effective in specific population of patients and reduce the number of treatment sessions needed to obtain an objective response

No abstract available

[en] Published data on mutations induced by ionizing radiation and 6 monofunctional alkylating agents, namely EMS, MMS, ENNG, MNNG, ENU and MNU, in different cell lines (Chinese hamster ovary, Chinese hamster lung V79, mouse lymphoma L5178 and human cells) were analysed so that radiation-equivalent chemical (REC) values could be calculated. REC values thus obtained for a given alkylating agent with different cell lines fall within a narrow range suggesting its validation in cultured mammalian cell systems including human. (orig.)