Metallothionein in isolated pancreatic islets of mice: induction by zinc and streptozotocin, a naturally occurring diabetogen.

Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn.kg-1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn.kg-1 or a single high dose of STZ (100 or 200 mg.kg-1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg.kg-1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3 x 40 respectively 5 x 40 mg STZ.kg-1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i.p. injection with Zn or STZ, in particular after repeated low doses of STZ.

Granulocyte colony-stimulating factor (G-CSF) treatment in a neutropenic leukemia patient with diffuse interstitial pulmonary infiltrates.

Adult respiratory distress syndrome (ARDS) in patients suffering from acute leukemia usually occurs during chemotherapy-induced neutropenia. In addition, intensified chemotherapy with high-dose cytosine arabinoside and mediastinal irradiation may contribute to the development of ARDS. This complication is usually refractory to conservative treatment with antibiotics, steroids, and mechanical ventilation. In this report, we describe a 25-year-old patient with acute lymphoblastic leukemia who developed ARDS during the phase of chemotherapy-induced neutropenia. Subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) at doses of 300-600 micrograms/day led to a prompt increase of peripheral granulocyte counts. With resolution of neutropenia, respiratory function gradually improved, and mechanical ventilatory support was stopped after 2 weeks. From this observation we surmise that the application of G-CSF may be an effective therapeutic approach for preventing the fatal outcome of ARDS in leukemia patients with bone marrow aplasia.

Remission rates following preoperative chemotherapy and radiation therapy in patients with breast cancer.

PURPOSE: To evaluate remission and breast-conservation rates after preoperative chemotherapy or chemo-radiotherapy (CT-RT). PATIENTS AND METHODS: Seventy-three patients with 74 biopsy-proven invasive breast cancers prospectively entered the protocol. Eighteen patients were treated by neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (chemotherapy group). Fifty-five patients with 56 tumors were treated with combined neoadjuvant chemo-radiotherapy, followed by surgery (chemo-radiotherapy group). Most patients of both treatment groups received 4 cycles of EC chemotherapy. In some patients with large tumors 3 cycles of CMF were added. Chemotherapy was followed by hormonal treatment with tamoxifen or LHRH agonists in case of positive hormone-receptor status. Preoperative radiotherapy was administered using 2 Gy fractions up to a total dose of 50 Gy, followed by a tumor boost of 6 to 11 Gy. The median overall treatment time was 41 days (range: 35 to 55 days). The median time interval between end of neoadjuvant therapy and surgery was 11 weeks (range: 10 to 22 weeks) and 27 weeks (range: 11 to 41 weeks) for the chemotherapy- and chemo-radiotherapy group. The median time interval between end of chemotherapy and the beginning of irradiation ranged between 2 and 8 weeks (median 4 weeks) in the chemo-radiotherapy group. RESULTS: Side-effects due to chemo- or radiotherapy were moderate and reversible. In the chemotherapy group 17/18 patients (94%) achieved a partial (pPR) and 1/18 patients (6%) a complete histopathological response (pCR). In the chemo-radiotherapy group 32/56 (57%) showed a pPR and 24/56 (43%) a pCR. The difference in complete remission is significant (Fisher's Exact Test: p = 0.004). In 45/74 cases (61%) the breast was preserved, immediate breast reconstructions with rectus myocutaneous flaps (TRAM) after mastectomy were performed in 8/74 cases (11%) and modified radical mastectomies without reconstruction were required in 21/74 cases (28%). The breast conservation rates were similar in both treatment groups. CONCLUSIONS: Even though the small number of patients in the present protocol does not permit definite conclusions, the results of combined modality treatment seem promising with regard to tumor remission within the treated breast and as a tool for breast conservation in advanced stage disease. On the basis of these encouraging data a prospective Phase-III study has been initiated.

Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia.

Conventional-dose Ara-C (200 mg/m2 d 1-5) combined with idarubicin (12 mg/m2 d 1-3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60-75) with AML according to the FAB criteria (M1 n = 3, M2 n = 10, M4 n = 6, M5 n = 2, M6 n = 2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.