ISSN:
0730-2312
Schlagwort(e):
Chemoprevention
;
cervical intraepithelial neoplasia
;
fluorescence spectroscopy
;
squamous intraepithelial lesion
;
Life and Medical Sciences
;
Cell & Developmental Biology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
Notizen:
The cervix is an ideal organ for chemoprevetion studies and the study of squamous carcinogenesis. In chemoprevention trial design, four factors are important: high-risk cohorts must be identified; suitable agents must be selected; study designs should include Phase I, II and III; and studies should include the use of surrogate endpoint biomarkers. High-risk cohorts can be selected for Phase I, II and III trial in the cervix, for example, patients with high grade lesion such as cervical interaepithelial neoplasia (CIN) grade 3 and carcinoma in situ (CIS). A Phase III trial might also include patients with lesions infected with ocogenic HPV types. The cervix is accessible and can be safely followed with Papanicolaou (Pap) smears and colposcopy. Suitable agents include those likely to work in squamous lesions, including retinoids, difluoromethylornithine β-carotene, and others. In Phase I chemopreventive studies, does are de-escalated rather than escalated, determining toxicity and optimal dose schedule. Phase II studies looking at effectiveness need placebo control groups since regression of high-risk lesions is possible. Phase III studies, now multicenteric, should be carefully designed and include wide patient representation in order to evaluate the risk-benefit ratio of therpy, focusing on cancer incidence reduction. Surrogate endpoint biomarkers include quantitative histopathology, biologic measures of histopathologic markers include nuclear grading (i.e., shape, area, optical density, texture), nuclear pleomerphism, ploidy, and nucleolar size and position. Biomarkers under study at the present time in the cervix include proliferation markers (PCNA), regulation markers (EGFR, ras, myc, p53, retinoic acid receptors, ODC, spermidine/spermine ratios), differentiation markers (involucrin, cornifin, keratins), and markers of genetic instability (chromosome polysomy). Fluorescent spectroscopy uses light to probe the biochemical properties of tissue. This technique provides an automated diagnosis in real time with comparable sensitivity and specificity to colposcopy and can be used to monitor lesions in chemoprevention trials. Recruitment designs for cervix studies need to include a large referral population and patients with sufficiently large lesions. Clinicians involved in such studies need to stress contraception and smoking cessation, deal with language barriers, and provide compensation for child care and parking to patients in order to increase compliance.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/jcb.240590914
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