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At least 91 records · Page 5Linked to original sources
PubMed1989

Phase II study of N-methylformamide, spirogermanium, and 4-demethoxydaunorubicin in the treatment of non-small cell lung cancer (EST 3583): an Eastern Cooperative Oncology Group study.

One hundred forty-four patients with non-small cell lung cancer, the majority (72%) of whom had received previous chemotherapy, were evaluable in this randomized phase II study of N-methylformamide (N-MF), spirogermanium, and 4-demethoxydaunorubicin. There were two partial responses, one each with spirogermanium and 4-demethoxydaunorubicin. There were eight life-threatening complications (mostly hematologic) and two lethal complications (N-MF, hematologic; 4-demethoxydaunorubicin, gastrointestinal). The overall survival ranged from 9 days to 533 days with a median of 17.6 weeks. The following factors were associated with poor survival: Poor initial performance status, prior weight loss, presence of liver or subcutaneous metastases.

Aged↗
PubMed1973

Alteration of the relative stability of dA-dT and dG-dC base pairs in DNA.

Several small alkylammonium ions can eliminate, or even reverse, the usual dependence of the DNA transition temperature on base composition. For example, in 3 M tetramethylammonium chloride, or 2.4 M tetraethylammonium chloride, DNAs of different base compositions all melt at a common temperature, and with a greatly decreased breadth of transition reflecting only the sequence-independent components of melting cooperativity. At still higher concentrations of such additives, dG.dC-rich DNAs melt at lower temperatures than dA.dT-rich molecules. Circular dichroism spectra show that these additives alter the structure of the DNA double helix very little at room temperature. This differential (base-specific) effect on helix stability is investigated with several small additives related to the tetraalkylammonium ions. Additives larger than tetraethylammonium ion have little differential effect on helix stability. Preferential binding of ions to dA.dT base pairs, requiring fit into a "groove" of DNA, is consistent with these data and with equilibrium binding studies. These differential effects can be distinguished from general destabilizing effects, which are independent of specific features of macromolecular conformation or chemistry. Possible experimental uses of this ability to alter the base-composition-dependent components of the stability of the DNA helix are discussed, as well as the insight this phenomenon provides into the molecular basis for the differential stability of dA.dT and dG.dC base pairs.

Animals↗
PubMed1987

Preliminary study on the suppression of experimental autoimmune encephalomyelitis in the Lewis rat with spirogermanium.

Spirogermanium (SG) is an azaspirane compound that incorporates the element germanium into a heterocyclic ring structure. It is currently being tested in phase II clinical trials as an anti-neoplastic agent and, in experimental animals, has suppressed adjuvant arthritis. In this study, SG suppressed experimental autoimmune encephalomyelitis in the Lewis rat. Suppression was a dose-dependent phenomenon and doses of 28 mg/kg and 40 mg/kg given intraperitoneally five through 14 days postinoculation gave significant protection. Perivascular inflammation in the central nervous system was also suppressed in animals receiving effective doses. Although these doses were well tolerated, cytoplasmic lamellar-bodies were found in the central nervous system of all SG-treated animals. Also, animals treated with SG developed diarrhea and weight loss, although histologic study of the gastrointestinal tract revealed no lesions.

Animals↗
PubMed1988

Effect of spirogermanium and radiation therapy on the 9L rat brain tumor model.

Spirogermanium (SPG) was investigated in the 9L rat brain tumor model in vivo and in vitro. Used at a single ip dose of 50 or 60 mg/kg or at 5 daily doses of 10 mg/kg, SPG was ineffective in prolonging survival of rats burdened with the intracerebrally implanted tumor, i.e., the median survival time (MST) was the same as that for the controls. Only a schedule of 3 X 20 mg SPG/kg every other day improved the MST compared with controls. Single-dose (20-Gy) radiation therapy (RT, cesium-137 whole-head irradiation) did prolong survival. However, when single-dose SPG was combined with RT (1 hr or 1 day before, or 1 hr after RT), the survival response was worse than after RT alone. When the daily SPG was combined with daily RT (5 doses of 6 Gy), survival was no better than after daily RT alone. In vitro, SPG produces a concentration-dependent, exponential decrease in cell survival as measured by colony formation assay. When combined with radiation, there is an additive effect on cell lethality. Aside from the possibility that SPG does not penetrate the rat brain tumor itself, we have no explanation why SPG shows some activity against human brain tumors and is cytotoxic against 9L cells in vitro, yet is both ineffective by itself and fails to potentiate RT in the 9L rat brain tumor model.

Animals↗
PubMed1986

Roles of adroxazine, a new heterocyclic hormone of the adrenals, and leucogenenol, a thymothyroid hormone, in the formation of blood cells.

Treatment of normal rats with the thymothyroid hormone leucogenenol accelerates the rate at which the 'functional' cells, neutrophils, red blood cells and lymphocytes, develop in the bone marrow from their corresponding committed precursor cells. Following the initial treatment of normal rats with leucogenenol, there is a temporary elevation in the bone marrow of the relative concentrations of myeloblasts, rubriblasts and lymphoblasts. It has now been found that bilaterally adrenalectomized rats have a different response from normal rats to treatment with leucogenenol. Although treatment of bilaterally adrenalectomized rats with leucogenenol accelerates the rate of development of their functional cells, the initial injection of leucogenenol is followed by a temporary decrease in the relative concentrations of myeloblasts, rubriblasts and lymphoblasts in their bone marrow. Additionally, adrenalectomized rats treated concurrently with tritiated thymidine and leucogenenol show a significant lower percentage of labeled cells in their bone marrow than do correspondingly treated normal rats. These results indicate that adrenalectomized rats have a lower than normal concentration of stem cells in their bone marrow that can be committed to become functional cells. Treatment with adroxazine, a new recently isolated heterocyclic hormone of the adrenals, causes adrenalectomized rats to respond as normal rats to the injection of leucogenenol. There is a temporary elevation of myeloblasts, rubriblasts and lymphoblasts in their bone marrow as well as a normal increase in the percentage of cells that are labeled following concurrent treatment with tritiated thymidine and leucogenenol. It may be concluded that treatment with adroxazine increases the rate of replication of uncommitted bone marrow stem cells while treatment with leucogenenol increases the rate at which committed cells develop into their respective functional cells. A scheme is presented to show the suggested roles that leucogenenol and adroxazine play in regulating the formation of blood cells.

Adrenal Glands↗