Microtubule depolymerization in Uromyces appendiculatus by three new antineoplastic drugs: combretastatin A-4, dolastatin 10 and halichondrin B

1998 ◽  
Vol 102 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Robert W. Roberson ◽  
Bruce Tucker ◽  
George R. Pettit
Keyword(s):  
Uromyces Appendiculatus ◽  
Antineoplastic Drugs ◽  
Microtubule Depolymerization ◽  
Halichondrin B ◽  
Dolastatin 10

Phase II study of eribulin mesylate (E7389) halichondrin b analog in patients with refractory breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1034-1034 ◽  
Author(s):  
J. L. Blum ◽  
B. Pruitt ◽  
C. J. Fabian ◽  
R. R. Rivera ◽  
D. E. Shuster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Microtubule Depolymerization ◽  
Prior Chemotherapy ◽  
Halichondrin B ◽  
Group 2 ◽  
Grade 3 ◽  
Cycle Group ◽  
Group 1

1034 Background: Eribulin is a structurally simplified analog of halichondrin B, which inhibits microtubule dynamics via a novel mechanism characterized by suppression of microtubule growth, lack of effect on microtubule depolymerization, and sequestration of tubulin into nonfunctional aggregates. This study was designed to assess the activity and tolerance of eribulin in chemotherapy refractory patients with advanced breast cancer. Methods: Eribulin was evaluated in a single-arm Phase II trial in female patients with refractory breast cancer, ECOG performance status of 0–1, measurable disease, and neuropathy ≤ Grade 2. Patients received ≥ 1 prior chemotherapy regimen, including an anthracycline and a taxane. Eribulin was administered as a 2–5 min IV bolus of 1.4 mg/m2 on Days 1, 8, and 15 of a 28-Day cycle (Group 1). The schedule was modified to Days 1 and 8 of a 21-Day cycle (Group 2), because of dose delays. The primary efficacy endpoint was ORR according to RECIST criteria based upon independent review (IR) of tumor assessment. Results: Of 104 patients enrolled, 103 received eribulin treatment: 70 in Group 1, 33 in Group 2. Median age was 55 yrs (range 32–84). Patients had received a median of 4 prior chemotherapy regimens (range 1–11). Sixty-one percent of tumors were ER+, 14% Her2/neu 3+, and 29% were triple (ER, PR, Her-2) negative. The incidence of dose interruption, delay, or omission during Cycle 1 was 63% (Group 1) and 18% (Group 2). The most common drug related toxicities were neutropenia (75%, Grades 3: 31%, Grade 4: 30%, febrile neutropenia: 3.9%), fatigue (52%, Grade 3: 2.9%, no Grade 4), alopecia (Grade 1/2: 41%), nausea (37%, Grade 3: 1%, no Grade 4), and anemia (36%, Grade 3: 1%, no Grade 4). Peripheral neuropathy occurred in 34% of patients (Grade 3: 3.9%, no Grade 4). Best overall response rate (all PR) by IR was 14.5% and 15.2% in Groups 1 and 2, respectively; the combined ORR was 14.7% (95 % CI: 9–23%). Median PFS was 85 days, and the 6 mo PFS rate was 31%. Conclusions: Eribulin given as a 2–5 min IV infusion on Days 1, 8 of a 21-Day cycle or Days 1, 8, 15 of a 28-Day cycle exhibited a 15% PR rate by IR and a low incidence of Grade 3 neuropathy in this heavily chemotherapy pretreated population. The most common toxicity was neutropenia. The 21-Day schedule had an acceptable toxicity profile. No significant financial relationships to disclose.

PHI-55: (NCI#7427): A phase I study of halichondrin B analog (E7389) in combination with cisplatin (CDDP) in advanced solid tumors: A CCC, NCI/CTEP-sponsored trial (grant U01 CA 062505).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2564-2564 ◽  
Author(s):  
Marianna Koczywas ◽  
Heinz-Josef Lenz ◽  
Joanne E. Mortimer ◽  
Anthony B. El-Khoueiry ◽  
Paul Henry Frankel ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Median Number ◽  
Treatment Schedule ◽  
Advanced Solid Tumors ◽  
Microtubule Depolymerization ◽  
Eligibility Criteria ◽  
Halichondrin B ◽  
Number Of Cycles ◽  
Dose Modifications ◽  
Tumor Types

2564 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of the marine sponge natural product Halichondrin B, which inhibits microtubule dynamics via a novel mechanism characterized by suppression of microtubule growth, lack of effect on microtubule depolymerization, and sequestration of tubulin into nonfunctional aggregates. Methods: The goals of this trial were to determine the DLT, the MTD, and PK of E7389 (administered on days 1, 8 and 15 every 28 days) in combination with CDDP (administered on day 1 every 28 days) in patients (pts) with advanced solid tumors. The protocol was amended after dose level 4 (E7389 1.4 mg/m2, CDDP 60 mg/m2) when it was not feasible to administer E7389 on day 15 due to neutropenia; the treatment schedule was changed to E7389 days 1 and 8 and CDDP day 1 every 21 days. Eligibility criteria included normal organ function and < 2 prior chemotherapy regimens. Results: To date, 36 pts have been treated (E7389 0.7-1.4 mg/m2 and CDDP 60-75 mg/m2). Median age 61 years; 19 males; the most common tumor types were lung (8), pancreatic (5), head and neck (6). 36% ECOG 0, 56% ECOG 1, 8% ECOG 2; Median number of cycles was 3 (1 – 8). There were 3 pts with DLT’s on the 28-day cycle: gr 4 febrile neutropenia (1.0/60); gr 3 anorexia/fatigue/hypokalemia (1.2/60); and gr 3 stomatitis/fatigue (1.4/60). There were 3 pts with DLTs treated on the 21-day schedule: gr 3 hypokalemia/hyponatremia (1.4/60); gr 4 mucositis (1.4/60); and gr 3 hypokalemia (1.2/75). With 2 DLTs out of 6 pts at E7389 1.4 mg/m2 and CDDP 60 mg/m2, E7389 was reduced, CDDP was escalated, and the MTD was determined to be E7389 1.2 mg/m2 and CDDP 75 mg/m2(1 patient out of 6 with a DLT). At the MTD, protocol defined dose modifications or delays were required in 2 of the 6 patients by cycle 2. Notably, all DLTs were observed in patients exposed to at least 2 prior lines of chemotherapy. Two pts had an unconfirmed PR (pancreatic, breast) and 2 had a PR (esophagus, transitional bladder). Conclusions: On a 21 day schedule,E7389 in combination with CDDP appears well tolerated and showed preliminary activity. The MTD was determined to be E7389 1.2 mg/m2 and CDDP 75 mg/m2. Clinical trial information: 00400829.

Effects of cisplatin treatment on the rat neurohypophysis

1986 ◽  
Vol 44 ◽  
pp. 122-123
Author(s):  
J.M. Fadool ◽  
P.J. Boyer ◽  
S.K. Aggarwal
Keyword(s):  
Side Effects ◽  
Urine Output ◽  
Morphological Changes ◽  
Limiting Factor ◽  
Antineoplastic Drugs

Cisplatin (CDDP) is currently one of the most valuable antineoplastic drugs available. However, it has severe toxic side effects of which nephrotoxicity is the major dose limiting factor in its use. It induces morphological changes in the kidney with hampered urine output. The present study is an effort to determine the influence of the drug on the neurohypophysis for any antidiuretic effects on the kidney.

Growth factors and the primary cilium in BALB/c 3T3 cells

1987 ◽  
Vol 45 ◽  
pp. 830-831
Author(s):  
R. W. Tucker ◽  
N. S. More ◽  
S. Jayaraman
Keyword(s):  
Growth Factors ◽  
Primary Cilium ◽  
Cultured Cells ◽  
Morphological Changes ◽  
Calcium Ionophore ◽  
Growth Stimulation ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
3T3 Cells ◽  
Microtubule Depolymerization

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.

scholarly journals Fungicidal Efficacy of Drying Plant Oils in Green Beans against Bean Rust (Uromyces appendiculatus)

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Vera Breiing ◽  
Jennifer Hillmer ◽  
Christina Schmidt ◽  
Michael Petry ◽  
Brigitte Behrends ◽  
...  
Keyword(s):  
Unsaturated Fatty Acids ◽  
Plant Protection ◽  
Linseed Oil ◽  
Uromyces Appendiculatus ◽  
Plant Oils ◽  
Bean Rust ◽  
Green Beans ◽  
Plant Oil ◽  
Water Emulsion ◽  
Tung Oil

As biorationals, plant oils offer numerous advantages such as being natural products, with low ecotoxicological side effects, and high biodegradability. In particular, drying glyceride plant oils, which are rich in unsaturated fatty acids, might be promising candidates for a more sustainable approach in the discussion about plant protection and the environment. Based on this, we tested the protective and curative efficacy of an oil-in-water-emulsion preparation using drying plant oils (linseed oil, tung oil) and a semi-drying plant oil (rapeseed oil) separately and in different mixtures. Plant oils were tested in greenhouse experiments (in vivo) on green beans (Phaseolus vulgaris L.) against bean rust (Uromyces appendiculatus). We observed that a 2% oil concentration showed no or very low phytotoxic effects on green beans. Both tested drying oils showed a protective control ranging from 53–100% for linseed oil and 32–100% for tung oil. Longer time intervals of 6 days before inoculation (6dbi) were less effective than shorter intervals of 2dbi. Curative efficacies were lower with a maximum of 51% for both oils when applied 4 days past inoculation (4dpi) with the fungus. Furthermore, the results showed no systemic effects. These results underline the potential of drying plant oils as biorationals in sustainable plant protection strategies.

Sign in / Sign up

Export Citation Format

Share Document