Abstract: Nucleic acid starting material composed of a collection of single stranded nucleic acid molecules is anchored and processed by a direction random printing method to produce a mixture of shorter random size DNA molecules well-suited for achieving substantially uniform global PCR amplification. The processing and global amplification method disclosed is especially useful in conjunction with subtractive hybridization procedures applied, for example, to the study of differential gene expression.

Abstract: The identification and sequencing of the BRCA2 gene is disclosed as well as the amino acid sequence of the corresponding BRCA2 polypeptides. BRCA2 alleles including those with mutations in the BRCA2 gene which are associated with a predisposition to develop cancer, especially breast and ovarian cancer are also disclosed. The present invention further relates to polypeptides encoded by the above nucleic acid. The present invention further relates to uses of much BRCA2 nucleic acid and BRCA2 polypeptides, in particular in the diagnostic, prognostic or therapeutic treatment of cancer.

Abstract: Novel compositions and methods are described for stimulating a patient's immune system to tumor cells which bear a gp72 tumor-associated antigen and thereby eliciting a tumoricidal effect. Anti-idiotypic human monoclonal antibodies and idiotopic regions thereof to primary antibodies which bind selectively to an antigenic determinant of gp72 are provided to mediate the humoral and cellular components of the patient's immune system. The immunogenic agents find use both in vivo and in vitro.

Abstract: O.sup.6 -hetarylalkyl- or naphthylalkylguanine derivatives of the formula ##STR1## wherein Y is H, ribosyl, deoxyribosyl, or R"XCHR',wherein X is O or S, R" and R"' are alkyl, or substituted derivatives thereof,R' is H, or alkyl or hydroxyalkylR is(i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocylic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hereto atom chosen from O, N, or S, or a substituted derivative thereof; or(ii) naphthyl or a substituted derivative thereofand pharmaceutically acceptable salts thereof, exhibit the ability to deplete O.sup.6 -alkylguanine-DNA alkyltransferase (ATase) activity.A process for preparation of the compounds is described. The compounds have utility in combination with alkylating agents in the chemotherapeutic treatment of tumour cells.

Abstract: There are disclosed herein 2-phenylbenzazole compounds having a 3'-substituent and a 4'-NR.sup.2 R.sup.6 substituent in the phenyl group where R.sup.5 and R.sup.6 are each hydrogen or alkyl, or where the $'-NR.sup.5 R.sup.6 substituent is N-acyl (or N-benzoyl). There are also disclosed 2-phenylbenzazole compounds in the form of 4'-N sulphamate salts. Such compounds exhibit significant selective cytotoxic activity in respect of tumor cells and provide potentially useful chemotherapeutic agents for selective treatment of a range of cancers.

Abstract: The invention provides a two component system for use in association with one another comprising:(a) a vector capable of expressing an enzyme at the surface of a cell; and(b) a prodrug which can be converted into an active drug by said enzyme, useful in the treatment of tumours.

Abstract: The invention provides pharmaceutical formulations for Immunizing against papillomavirus tumors or lesions. Formulations may be selected from the group consisting of: (i) a formulation which comprises a papillomavirus (PV) L2 protein or fragment thereof that is effective to provide a protective effect to lessen the occurrence and severity of lesions or tumors caused by PV infection and an aluminum compound; (ii) a formulation which comprises a bovine papillomavirus (BPV) L2 protein or said fragment thereof and an aluminum compound: (iii) a formulation which comprises a BPV4 L2 protein or said fragment thereof and an aluminum compound; (iv) a formulation which comprises a BPV-4 protein or said fragment thereof and an adjuvant; (v) a formulation which comprises a BPV-4 L2 protein or said fragment thereof and an adjuvant; and (vi) a formulation which comprises a BPV4 protein or said fragment thereof and an aluminum compound.

Abstract: The invention provides a two component system for gene-directed enzyme prodrug therapy which comprises: (a) a vector which encodes a carboxypeptidase which is expressed within a cell; and (b) a prodrug which can be converted into an active drug by said carboxypeptidase, useful in the treatment of tumours.

Abstract: The invention provides compounds of formula (I) and (II) wherein X and Y are independently chlorine, bromine, iodine, a mesyl group CH.sub.3 SO.sub.3 or a tosyl group OSO.sub.2 phenyl (wherein phenyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C.sub.1-4 alkyl, halogen, cyano or nitro; R.sup.1 and R.sup.2 are independently 1 to 4 optional substituents; Z.sup.1 and Z.sup.2 are each independently --O-- or --NH--; R.sup.3 is hydrogen, t-butyl or allyl; Z.sup.3 is a hydrocarbyl group such as carboxyethyl, optionally containing heteroatoms, and physiologically acceptable derivatives thereof. The compounds can be converted in situ into nitrogen mustard agents by the actions of enzymes such as carboxypeptidase or nitroreductase and are useful for the treatment of cancer.

Abstract: The present invention provides compounds of formula (I) and (II) which may be used as anticancer drugs.

Abstract: A prodrug of the formula (I): ##STR1## where R.sup.1 is a group such that the compound R.sup.1 NH.sub.2 represents actinomycin D, doxorubicin, mitomycin C, or a nitrogen mustard of the formula (IV): ##STR2## a prodrug of the formula (II): ##STR3## where R.sup.2 is a group such that the compound R.sup.2 OH is a phenolic nitrogen mustard; and processes whereby the prodrugs shown above are made in which a prodrug precursor compound is reacted with 4-nitrobenzyl chloroformate under anhydrous conditions.

Abstract: Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalyzed reactions.

Abstract: A system is disclosed which comprises: (i) a viral vector comprising a nucleotide sequence encoding a nitroreductase, which nitroreductase is capable of converting a prodrug into a cytotoxic drug; and (ii) a prodrug capable of being converted into a cytotoxic drug by the nitroreductase encoded by the vector. The disclosed invention also includes methods for killing cancerous and/or non-cancerous cells using the system described above. Included in the invention are methods for killing cells in vitro by introducing a vector encoding a nitroreductase into the cells, and then by providing a prodrug to the cells growing in vitro. Also included are methods in which cancerous and/or non-cancerous cells are killed in vivo in an animal or human by administering the vector and prodrug directly to cells of the animal or human.

Abstract: The present invention provides certain 6-hetarylalkyloxy pyrimidine derivatives of formula II ##STR1## wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a substituted derivative thereof,R.sup.2 is selected from H, C.sub.1 -C.sub.5 alkyl, halogen or NH.sub.2,R.sup.4 and R.sup.5 which are the same or different are selected fromH, NH.sub.2 or NO.sub.n where n=1 or 2, or R.sup.4 and R.sup.5 together with the pyrimidine ring form a 5-or 6-membered ring structure containing one or more heterocyclic atoms, and pharmaceutically acceptable salts thereof, exhibit the ability to deplete O.sup.6 -alkylguanine-DNA alkyltransferase (ATase) activity.

Abstract: The invention provides an antibody specific for carcinoembryonic antigen (CEA) which has a dissociation constant (Kd; of less than 5.0 nM for said antigen. The antibody is generally a single chain Fv (scFv) antibody. The antibody was initially obtained by screening a bacteriophage library for phage expressing high affinity CEA antibody. The antibody is useful for diagnosis and therapeutic treatment of colorectal tumors.

Abstract: There are disclosed herein benzazole compounds, exemplified by 2-(4-aminophenyl)benzothiazole and analogues or salts thereof, which exhibit very significant selective cytotoxic activity in respect of tumor cells, especially breast cancer cells, and which provide potentially useful chemotherapeutic agents for treatment of breast cancer.

Abstract: The present invention provides compounds of the formula (I) wherein each R.sup.1, which may be the same or different, is hydrogen, C.sub.1-4 alkyl, or an electron withdrawing group selected from the group consisting of CF.sub.3 CH.sub.2 or CH.sub.2 C.tbd.CH, R.sup.2 is hydrogen, C.sub.1-4 alkyl, or an electron withdrawing group selected from the group consisting of CF.sub.3 CH.sub.2 or CH.sub.2 C.tbd.CH. The compounds are analogs of trimelamol which have comparable activity but enhanced stability, and are useful as anticancer agents, particularly against ovarian cancer.

Abstract: The invention provides a compound which is a 3-fluorobenzamide of the formula (A) ##STR1## wherein R-NH is the residue of an .alpha.-amino acid R-NH.sub.2 or oligopeptide R-NH.sub.2, and M is a nitrogen mustard group of the formula ##STR2## wherein Y and L, which may be the same or different in a molecule, are leaving groups; or a pharmaceutically acceptable salt thereof. The compounds are useful as prodrugs for treating cancer.

Abstract: A prodrug of the formula (I): ##STR1## where R.sup.1 is a group such that the compound R--NH.sub.2 represents actinomycin D, doxorubicin, mitomycin C, or a nitrogen mustard of the formula (IV): ##STR2## a prodrug of the formula (II): ##STR3## where R.sup.1 is a group such that the compound R.sup.2 OH is a phenolic nitrogen mustard; and processes whereby the prodrugs shown above are made in which a prodrug precursor compound is reacted with 4-nitrobenzyl chloroformate under anhydrous conditions.

Abstract: A prodrug of the general formula FTLi-(PRT)m, where m is an integer from 1 to 5; FTLi is a ras inhibitor such as a farnesyltransferase inhibitor compound, such as Ia, Ib, Ic; and PRT represents m protecting groups or a precursor thereof, such as compound XVI, which are capable of being cleaved from the ras inhibitor by the action of a enzyme.