thioguanine-anhydrous and Prostatic-Neoplasms

thioguanine-anhydrous has been researched along with Prostatic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for thioguanine-anhydrous and Prostatic-Neoplasms

Article	Year
Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenosine phosphorylase, an exploitable tumor target. Molecular cancer therapeutics, 2012, Volume: 11, Issue:3 Castrate-resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumor sequencing program, a patient tumor was analyzed using Illumina genome sequencing and a matched renal capsule tumor xenograft was generated. Both tumor and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2, and ARF genes. It is rare for this deletion to occur in primary prostate tumors, yet approximately 10% express decreased levels of methylthioadenosine phosphorylase (MTAP) mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it seems that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient-derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers as deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumors at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology. Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Chromosome Deletion; Chromosomes, Human, Pair 9; Cyclin-Dependent Kinase Inhibitor p16; Deoxyadenosines; Humans; Male; Mice; Mice, Inbred NOD; Mice, SCID; Neuroendocrine Tumors; Prostatic Neoplasms; Purine-Nucleoside Phosphorylase; Sequence Analysis, DNA; Thioguanine; Thionucleosides; Treatment Outcome; Urethral Neoplasms; Xenograft Model Antitumor Assays	2012
Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives. European journal of medicinal chemistry, 2007, Volume: 42, Issue:3 A series of arylidenehydrazides (3a-3i) were synthesized from [6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The structures of new compounds were determined by analytical and spectral (IR, (1)H NMR, (13)C NMR, EIMS) methods. The synthesized compounds (3a-3i) were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. Compounds 3a-3c, 3h and 3i which passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Compounds 3c demonstrated the most marked effects on a prostate cancer cell line (PC-3, log(10)GI(50) value<-8.00). Topics: Antineoplastic Agents; Drug Screening Assays, Antitumor; Humans; Imidazoles; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Prostatic Neoplasms; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Thiazoles	2007

Article

Year

Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenosine phosphorylase, an exploitable tumor target.

Molecular cancer therapeutics, 2012, Volume: 11, Issue:3

Castrate-resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumor sequencing program, a patient tumor was analyzed using Illumina genome sequencing and a matched renal capsule tumor xenograft was generated. Both tumor and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2, and ARF genes. It is rare for this deletion to occur in primary prostate tumors, yet approximately 10% express decreased levels of methylthioadenosine phosphorylase (MTAP) mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it seems that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient-derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers as deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumors at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Chromosome Deletion; Chromosomes, Human, Pair 9; Cyclin-Dependent Kinase Inhibitor p16; Deoxyadenosines; Humans; Male; Mice; Mice, Inbred NOD; Mice, SCID; Neuroendocrine Tumors; Prostatic Neoplasms; Purine-Nucleoside Phosphorylase; Sequence Analysis, DNA; Thioguanine; Thionucleosides; Treatment Outcome; Urethral Neoplasms; Xenograft Model Antitumor Assays

2012

Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives.

European journal of medicinal chemistry, 2007, Volume: 42, Issue:3

A series of arylidenehydrazides (3a-3i) were synthesized from [6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The structures of new compounds were determined by analytical and spectral (IR, (1)H NMR, (13)C NMR, EIMS) methods. The synthesized compounds (3a-3i) were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. Compounds 3a-3c, 3h and 3i which passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Compounds 3c demonstrated the most marked effects on a prostate cancer cell line (PC-3, log(10)GI(50) value<-8.00).

Topics: Antineoplastic Agents; Drug Screening Assays, Antitumor; Humans; Imidazoles; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Prostatic Neoplasms; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Thiazoles

2007