The Use of Mechlorethamine, Cyclophosphamide, And Uracil Mustard in Neoplastic Disease: A Cooperative Study

Gold, G. Lennard; Shnider, Bruce I.; Salvin, G A B Leonard; Schneiderman, Marvin A.; Colsky, Jacob; Owens, Albert H.; Krant, Melvin J.; Miller, Sherwood P.; Frei, Emil; Hall, Thomas C.; Spurr, Charles L.; McIntyre, O. Ross; Hoogstraten, Barth; Holland, James F.

doi:10.1177/009127007001000206

Cited by 14 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechlorethamine ( Figure 4A ) is a frequently prescribed drug used to treat Hodgkin lymphoma and several other cancers ( Gold et al 1970 ). Mechlorethamine is an alkylating agent and inhibits DNA replication via the formation of interstrand crosslinks ( Millard et al 1990 ; Rink and Hopkins 1995 ).…”

Section: Resultsmentioning

confidence: 99%

Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants

Ojini

Gammie

2015

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

Resistance to cancer therapy is a major obstacle in the long-term treatment of cancer. A greater understanding of drug resistance mechanisms will ultimately lead to the development of effective therapeutic strategies to prevent resistance from occurring. Here, we exploit the mutator phenotype of mismatch repair defective yeast cells combined with whole genome sequencing to identify drug resistance mutations in key pathways involved in the development of chemoresistance. The utility of this approach was demonstrated via the identification of the known CAN1 and TOP1 resistance targets for two compounds, canavanine and camptothecin, respectively. We have also experimentally validated the plasma membrane transporter HNM1 as the primary drug resistance target of mechlorethamine. Furthermore, the sequencing of mitoxantrone-resistant strains identified inactivating mutations within IPT1, a gene encoding inositolphosphotransferase, an enzyme involved in sphingolipid biosynthesis. In the case of bactobolin, a promising anticancer drug, the endocytosis pathway was identified as the drug resistance target responsible for conferring resistance. Finally, we show that that rapamycin, an mTOR inhibitor previously shown to alter the fitness of the ipt1 mutant, can effectively prevent the formation of mitoxantrone resistance. The rapid and robust nature of these techniques, using Saccharomyces cerevisiae as a model organism, should accelerate the identification of drug resistance targets and guide the development of novel therapeutic combination strategies to prevent the development of chemoresistance in various cancers.

show abstract

Section: Resultsmentioning

confidence: 99%

Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants

Ojini

Gammie

2015

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…Finally, previous work of the CALGB indicated that the duration of drug therapy in malignant disorders influenced the quality and duration of response [9] . This observation raised a reasonable question as to whether the same was true for the non-Hodlymphomas.…”

Section: Background Of the Studymentioning

confidence: 93%

“…unequivocally active against NHL were alkylating agents [9] , vinca alkaloids [6], and corticosteroids [lo]. The CALGB study immediately preceding this one (No.6703) sug.…”

Section: Background Of the Studymentioning

confidence: 99%

Combination chemotherapy for non‐Hodgkin lymphomas: A ten year follow‐up study

Hayes

Pajak

Rege

et al. 1979

Med. Pediatr. Oncol.

Self Cite

View full text Add to dashboard Cite

In 1968 the Cancer and Acute Leukemia Group B (CALGB) demonstrated optimal control of disseminated non-Hodgkin lymphomas (NHL) with vincristine-prednisone induction followed by cyclophosphamide maintenance. A study was then begun to determine whether four drugs in combination or sequence could achieve greater control. NHL patients at each participating CALGB institution were randomly assigned to one of three regimens:I) Cyclic vincristine-streptonigrin alternating every 2 weeks with cyclophosphamide-prednisone up to 155 days; II) Sequential treatment with the same 4 drugs taken singly up to 182 days; and III) Vincristine-prednisone induction for 6 weeks followed by cyclophosphamide maintenance. Results are now reported after a 10 year follow-up period. The 203 evaluable patients are those on whom Rappaport histopathologic classification was available. Frequency of complete-response did not differ significantly among the three regimens: I) 38%; II) 30%; and III) 45%. Remission durations were significantly longer among patients receiving maintenance therapy. After ten years, two patients from Regimen I, one from Regimen II, and five from Regimen III remain alive and well. It was concluded that neither of the four-drug regimens conferred a significant advantage in terms of response rate or survival time over the standard treatment.

show abstract

“…Survival was best with regimens 2 and 3. 1 During the ensuing years, the vinca alkaloids were recognized as active drugs in the therapy of Hodgkin's disease, and it became important to study the relative value of this group of drugs and the details of their opti¬ mal use, such as whether remission induced by a drug should be followed by maintenance therapy.…”

mentioning

confidence: 99%

Chemotherapy of Hodgkin's Disease in Studies by Acute Leukemia Group B

Nissen¹

1973

Arch Intern Med

View full text Add to dashboard Cite

The Use of Mechlorethamine, Cyclophosphamide, And Uracil Mustard in Neoplastic Disease: A Cooperative Study

Cited by 14 publications

References 9 publications

Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants

Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants

Combination chemotherapy for non‐Hodgkin lymphomas: A ten year follow‐up study

Chemotherapy of Hodgkin's Disease in Studies by Acute Leukemia Group B

Contact Info

Product

Resources

About