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Diagnosis and treatment of cancer

a cancer and cancer technology, applied in the field of cancer diagnosis and treatment, can solve the problems of inability to fit the sigmoid curve to the data, two extremes of this curve were unknown or undetermined, and the pharmacological properties of the vgs current in the rat mat-lylu cell were not consistent with those reported

Inactive Publication Date: 2006-07-27
IMPERIAL INNOVATIONS LTD
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  • Abstract
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Benefits of technology

[0004] Carcinoma of the prostate has become a most significant disease in many countries and it is the most commonly diagnosed malignancy in men in the western world, its occurrence increasing significantly with age. Over the last 20 years the mortality rates have doubled and it is now the second commonest cause of male cancer deaths in the Western world (Wingo et al (1995) Cancer J. Clin. 45, 8-30; Mortality Statistics: Cause England and Wales. OPCS DH2 19, 1993, Her Majesty's Stationery Office). The prevalence of prostate cancer has increased by 28% in the last decade and this disease now accounts for 12% of the total cancers of men in England and Wales (Cancer Statistics: Registrations England and Wales. OPCS MBI No 22, 1994, Her Majesty's Stationery Office; Foster et al (1999) Br. J. Urol. 83, 171-194). By the year 2018 it is expected to be the biggest killer with 50% of the male population suffering from it (80% by age 80 years). Recent evidence suggests that prostate cancer is also increasing amongst younger men as well (Br J Cancer (1999) 79, 13-17). These increases and the recent deaths of many public figures from prostatic cancer have served to highlight the need to do something about this cancer. It has been suggested that the wider availability of screening may limit mortality from prostate cancer.
[0179] In addition to using carbodiimides for the direct formation of peptide bonds, EDC also can be used to prepare active esters such as N-hydroxysuccinimide (NHS) ester. The NHS ester, which binds only to amino groups, then can be used to induce the formation of an amide bond with the single amino group of the doxorubicin. The use of EDC and NHS in combination is commonly used for conjugation in order to increase yield of conjugate formation (Bauminger & Wilchek, supra, 1980).

Problems solved by technology

However, the pharmacological properties of the VGS currents in the rat MAT-LyLu cells were not consistent with those reported for this VGSCα.
However, the two extremes of this curve were unknown or undetermined for the SQT-PCR data (i.e. the initial mass of cDNA at zero cycles was unknown, and the final product mass at the end of the PCR undetermined).
Thus, a sigmoid curve could not be fitted to the data.
The specific PCRs for PN1, hNe—Na, RB2, HB2, hNa6 and HB3 produced multiple VGSCα products, due to alternative splicing, making determination of the VGSCαs' levels of expression more difficult.
However, unlike such methods, degenerate screens also yield quantitative information.
The utility of PCR for quantitative analysis is limited by the loss of quantitation at a certain stage of amplification beyond which the reaction ceases to amplify exponentially and eventually reaches a plateau (Morrison, C.
Second, as regards prostate cancer itself, a serious limitation in the current management methods is that the available markers for the metastatic phenotype (such as prostate specific antigen) are not reliable (59, 60).
Thus, clinically important cancers cannot readily be distinguished from those which are clinically unimportant and do not require aggressive treatment (which is associated with high patient morbidity).

Method used

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  • Diagnosis and treatment of cancer
  • Diagnosis and treatment of cancer
  • Diagnosis and treatment of cancer

Examples

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example 3

Voltage-Gated Na+ Channel Expression Correlates with Pathological Progression in Human Prostate Cancer

[0379] Previous electrophysiological studies have shown that functional voltage gated Na+ channels (VGSCs) are expressed selectively by highly metastatic cell lines of rat (MAT-LyLu) and human (PC-3) prostate cancer. Furthermore, blockage of these channels with tetrodotoxin significantly reduced the cells' invasion in vitro (Grimes et al. (1995) FEBS Letts. 369, 290-294; Laniado et al (1997) Am. J. Pathol. 150 1213-1221. Direct, positive correlation between invasiveness and Na+ channel protein expression by several different rat and human prostate cancer cell lines was subsequently demonstrated by Smith et al. (1998) FEBS Lens. 423,19-24. However, it is not known whether VGSC expression occurs in human prostate cancer in vivo, and if so, whether the levels of expression relate to the metastatic profile of the constituent malignant epithelial cells.

[0380] Immunohistochemical locali...

example 4

Regulation of VGSC Function in Prostate Cancer Cell Lines

[0382] VGSC functional expression in rodent MAT-LyLu cells was investigated. Epidermal growth factor (EGF) upregulates VGSC functional expression. As shown in FIG. 9, exogenous EGF potentiates the functional VGSC expression. This effect is blocked by co-application of EGF receptor kinase inhibitor (AG1478; Calbiochem, San Diego, Calif., USA). Application of EGF receptor antibody (Oncogene, Cambridge, Mass., USA) also reduces the basal VGSC current implying that the phenomenon occurs endogenously.

[0383] Other growth factors (for example nerve growth factor) and hormones (including androgens) may have similar effects.

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Abstract

A method of diagnosing cancer in a human patient comprising the steps of (i) obtaining a sample containing nucleic acid and / or protein from the patient; and (ii) determining whether the sample contains a level of hNeNa voltage-gated Na+ channel nucleic acid or protein associated with cancer. A method of treating cancer comprising the step of administering to the patient an agent which selectively prevents the function of hNe—Na voltage-gated Na+ channel. A genetic construct comprising a nucleic acid encoding a molecule capable of preventing the function of hNeNa voltage-gated Na+ channel expressed in a cell. The methods and compositions are particularly suited to prostate cancer.

Description

[0001] The present invention relates to methods of determining whether a patient has cancer and whether the cancer is likely to metastasise; and it relates to methods of treating cancer, particularly prostate cancer. [0002] Cancer is a serious disease and a major killer. Although there have been advances in the diagnosis and treatment of certain cancers in recent years, there is still a need for improvements in diagnosis and treatment. [0003] Cancer is a genetic disease and in most cases involves mutations in one or more genes. There are believed to be around 60,000 genes in the human genome but only a handful of these genes have been shown to be involved in cancer. Although it is surmised that many more genes than have been presently identified will be found to be involved in cancer, progress in this area has remained slow despite the availability of molecular analytical techniques. This may be due to the varied structure and function of genes which have been identified to date whi...

Claims

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Application Information

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IPC IPC(8): C12Q1/68G01N33/574G01N33/50A61K31/7115A61K38/00A61K38/43A61K45/00A61K48/00A61P35/00C07K14/47C07K19/00C12N1/15C12N1/19C12N1/21C12N5/10C12N15/09C12N15/113C12Q1/6886G01N33/15G01N33/566
CPCA61K38/00C12N15/113C12Q1/6886C12Q2600/158G01N33/574C12Q2600/136A61P35/00
Inventor ALI DJAMGOZ, MUSTAFADISS, JAMESFRASER, SCOTT
Owner IMPERIAL INNOVATIONS LTD
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