ABSTRACT
Several derivatives of 2,5-diaziridinyl-3-phenyl-1,4-benzoquinone have been synthesized and their cytotoxicities in six different human cancer cell lines (H460, H596, HT29, BE, K562 and A2780) have been determined. It was observed that certain phenol-ester derivatives were significantly more cytotoxic in all of the cell lines investigated. These esters were shown to be cleaved by esterases to form a stable meta-phenol and an unstable para-phenol. The meta-phenol was also highly cytotoxic. Several of these compounds were studied in detail using DNA cross-linking, clonogenic, apoptosis and flow cytometry assays. It is proposed that although the phenol-esters and the phenols can efficiently cross-link DNA, this mechanism alone is not sufficient to explain the toxicities of these compounds.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzoquinones/chemical synthesis , Benzoquinones/pharmacology , Esters/chemical synthesis , Esters/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Clone Cells/drug effects , Cross-Linking Reagents , Electrophoresis , Esterases/chemistry , Flow Cytometry , Humans , Indicators and Reagents , Molecular Conformation , NAD(P)H Dehydrogenase (Quinone)/metabolism , Stereoisomerism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Image-guided core biopsy (IGCB) of nonpalpable mammographic abnormalities has gained attention as an alternative to needle-localized breast biopsy (NLB). This study evaluated IGCB in the diagnostic workup of patients with nonpalpable mammographic lesions suspicious for cancer. Eighty-six patients who underwent IGCB were compared to 85 patients who underwent NLB for the diagnosis of mammographic lesions suspicious for cancer. The incidence of positive margins was less in patients who subsequently underwent needle-localized resection in the IGCB group than in the NLB group (29 and 65%; P < 0.0001). The volume of excision was greater for patients in the IGCB group than for the NLB group (106 cm3 and 52 cm3; P < 0.0001). Patients in the IGCB group averaged 1.1 operative procedures compared with patients in the NLB group, who required an average of 1.9 operative procedures. The mean charge for an IGCB was $1011 compared to $2975 for a NLB. Subset analysis of 32 spiculated masses from the IGCB group and 21 from the NLB group showed similar advantages of IGCB over NLB. The preoperative use of IGCB for mammographically suspicious lesions can reduce the incidence of positive surgical margins and the number of surgical procedures required. The use of IGCB allows for a more efficient diagnostic workup and less expense to the patient.
Subject(s)
Biopsy, Needle/methods , Breast Neoplasms/diagnosis , Diagnostic Imaging , Adult , Aged , Aged, 80 and over , Biopsy/economics , Biopsy/methods , Biopsy, Needle/economics , Female , Humans , Mammography , Middle Aged , Palpation , Retrospective StudiesSubject(s)
Aerospace Medicine , Pneumothorax/therapy , Adult , Chest Tubes , Drainage , Emergencies , Female , HumansABSTRACT
Analysis of 320 cancers found in a screened population between August 1985 and May 1990 revealed 77 cancers that were "missed" at screening mammography. The missed lesions consisted of cancers incorrectly diagnosed after mammography (false-negative results) but visible in retrospect (n = 19); cancers correctly diagnosed after mammography but visible in retrospect on an earlier mammogram (n = 47); and cancers that went undetected by the first of two readers (n = 11). Missed lesions were categorized according to type of miss, reason for the miss, breast density, lesion features, and lesion location. The missed lesion were compared with 121 cancers that were correctly diagnosed at screening mammography. The missed cancers occurred in women with denser breasts (P = .046), were less likely to demonstrate malignant microcalcifications, and were more likely to demonstrate a developing opacity as an indication of cancer (P = .005). An understanding of the characteristics of missed lesions may be a valuable aid in increasing the sensitivity of screening mammography.
