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E L Levine

Publications and source records attributed to E L Levine.

16 recordsLinked to original sources
PubMed2003

Influence of intrinsic radiosensitivity on the survival of breast cancer patients.

PURPOSE: The association between enhanced intrinsic radiosensitivity, measured by the level of chromosome damage induced in either the G2 or G0 phases of the cell cycle, and the risk of breast cancer has been well demonstrated. Although not originally designed for this purpose, early studies are now sufficiently mature (median follow-up 4.2 years) to enable an assessment of the impact of radiosensitivity on patient outcome. MATERIALS AND METHODS: Breast cancer patients assessed in previous studies of G2 and G0 lymphocyte chromosomal radiosensitivity between 1993 and 1997 were identified. Tumour characteristics, recurrence and survival data were obtained from clinical records and outcomes were compared between those identified as having normal and elevated radiosensitivity in the two assays. RESULTS: There was a significant association between G0 sensitivity and tumour grade (p=0.03), but otherwise there were no associations in these series between radiosensitivity in the two assays and tumour characteristics. Overall survival in this cohort of patients was high (94% at 5 years) and there was no association between the G2 or G0 assay results and outcome as measured by cancer-specific survival or local recurrence. CONCLUSIONS: Radiosensitivity, as measured by these two assays, was not a strong prognostic factor following standard radiotherapy treatment. However, the statistical power of the present study was limited and modest prognostic utility could not be discounted. Further studies designed specially to investigate outcome are needed, possibly in association with trials of altered radiotherapy fractionation.

Aged↗
PubMed2003

Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial.

BACKGROUND: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. PATIENTS AND METHODS: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m(2) twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m(2) with i.v. leucovorin 20 mg/m(2) on days 1-5, repeated every 28 days (n = 974). RESULTS: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or > or = 65 years old. CONCLUSIONS: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cancer

Administration, Oral↗
PubMed2002

Non-invasive pulsed ultrasound quantification of the resolution of basal cell carcinomas after photodynamic therapy.

The probability of local control of basal cell carcinomas (BCC) treated by photodynamic therapy (PDT) depends strongly on lesion thickness, thicker lesions often requiring two treatments. We examine the utility of 20 MHz pulsed ultrasound (US) for the non-invasive measurement of thickness and rate of regression after PDT treatment. PDT was by topically applied 20% aminolaevulinic acid, followed at 6 h by a standard 100 J/cm(2) of 630 nm light. Patients ( n=60) were selected as being difficult to treat with existing modalities for reasons of likely poor quality of healing or of cosmesis in this very largely elderly population. Ultrasound 'A' scans were made immediately before treatment, and at first and subsequent follow-ups. Parameters measured non-invasively for BCC, adjacent normal skin, and for fibroses after previous conventional therapies, were (a) thickness of skin or lesion, (b) linear density of ultrasound echoes and (c) linear density of high-amplitude echoes. Prior to treatment, median skin thickness (to the dermal/subcutaneous boundary) was 2.6 mm (range 1.2-5.7), fibroses 2.5 mm (1.4-5.6) and BCC 1.5 mm (0.5-4.4). Median linear density of echoes for normal skin, fibroses and BCC plus underlying tissue were 5.6, 5.5 and 4.5, respectively, the BCC values being significantly lower ( p=0.002). The corresponding medians for high-amplitude echoes were 1.9, 1.9 and 1.1 (skin or fibrosis versus BCC, p=0.001). Patients whose BCCs appeared clinically to be controlled at up to 220 days after a single treatment, all had values of ultrasound parameters corresponding to skin/fibrosis and were significantly different from measurements on the same site prior to treatment. Patients whose tumours appeared to be reverting to the original BCC ultrasound pattern were subsequently found to be recurring as judged clinically. Non-invasive pulsed ultrasound indicates that rates of resolution vary widely between BCC of similar initial thickness and that the probability of clearance of BCC by PDT is determined largely by the deepest, sometimes small, regions within a lesion, with the overall area being relatively unimportant.

Adult↗
PubMed2000

The use of cryopreserved lymphocytes in assessing inter-individual radiosensitivity with the micronucleus assay.

PURPOSE: The feasibility of using cryopreserved lymphocytes to detect inter-individual differences in chromosomal radiosensitivity was investigated. Typically, such studies are conducted with fresh blood samples but, in a clinical setting, when availability of samples is unpredictable, this is not always convenient. The sensitivity of 23 normal healthy donors, 11 breast cancer patients who had shown severe acute skin reactions to radiotherapy and seven ataxia telangiectasia (A-T) heterozygotes was determined. MATERIALS AND METHODS: Thawed lymphocytes were exposed to high (HDR) or low dose rate (LDR) gamma irradiation (3.5 Gy) in Go, stimulated with PHA, treated with cytochalasin-B 24 h later and then harvested at 90 h for the determination of micronucleus (MN) yields in binucleate cells. RESULTS: Each normal donor was tested one to three times. Mean MN yields were 76.1 +/- 9.3/100 cells at HDR and 44.5 +/- 5.3 at LDR, giving an LDR sparing effect of 39.6 +/- 9.3%. A relatively high proportion of tests failed to yield sufficient binucleate cells for analysis. Inter-experimental variability was also high and it was not possible to demonstrate inter-individual differences in sensitivity in spite of the use of an internal control sample from a single normal donor in each experiment. There was a small but significant increase in radiation-induced MN in the breast cancer patients compared with the normals at LDR (but not at HDR), but a complete overlap with the normal range. There was no increase in sensitivity in the A-T heterozygotes at HDR. The LDR samples failed because the LDR protocol reduced proliferation rates, and radiation-induced mitotic inhibition in this group was higher than in normals. CONCLUSIONS: In comparison with previous experience with fresh blood samples, the use of frozen lymphocytes is not as satisfactory because: (1) experimental failures are higher; (2) inter-experiment variability is higher: (3) dose-rate sparing is lower, suggesting poorer repair; and (4) the ability to discriminate between breast cancer cases and normals is probably lower.

Adult↗
PubMed1998

Radiation-induced micronucleus induction in lymphocytes identifies a high frequency of radiosensitive cases among breast cancer patients: a test for predisposition?

Enhanced sensitivity to the chromosome-damaging effects of ionizing radiation is a feature of many cancer-predisposing conditions. We previously showed that 42% of an unselected series of breast cancer patients and 9% of healthy control subjects showed elevated chromosomal radiosensitivity of lymphocytes irradiated in the G2 phase of the cell cycle. We suggested that, in addition to the highly penetrant genes BRCA1 and BRCA2, which confer a very high risk of breast cancer and are carried by about 5% of all breast cancer patients, there are also low-penetrance predisposing genes carried by a much higher proportion of breast cancer patients, a view supported by recent epidemiological studies. Ideally, testing for the presence of these putative genes should involve the use of simpler methods than the G2 assay, which requires metaphase analysis of chromosome damage. Here we report on the use of a simple, rapid micronucleus assay in G0 lymphocytes exposed to high dose rate (HDR) or low dose rate gamma-irradiation, with delayed mitogenic stimulation. Good assay reproducibility was obtained, particularly with the HDR protocol, which identified 31% (12 out of 39) of breast cancer patients compared with 5% (2 out of 42) of healthy controls as having elevated radiation sensitivity. In the long term, such cytogenetic assays may have the potential for selecting women for intensive screening for breast cancer.

Adult↗
PubMed1995

Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma.

Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy.

Adult↗
PubMed1995

Technical note: the efficacy of megavoltage imaging in the radical radiotherapy of non-small cell lung cancer.

Megavoltage imaging (MVI) has been used to obtain digital images of treatment fields during therapy for non-small cell lung cancer. Tumours were seen in all 33 cases studied and in three cases MVI was used to improve the set-up. It is concluded that in the setting of radical radiotherapy for non-small cell lung cancer this is an appropriate technique for the verification and correction of field position and is an aid to quality assurance.

Aged↗
PubMed1984

Attachment to and degradation of collagen substrata by adenovirus-transformed cells of varying tumorigenicity.

The interaction of adenovirus-transformed cells of different tumorigenicity with different collagen substrata has been investigated. The adenovirus type 2 (Ad2)-transformed cells are nontumorigenic in syngeneic rats while, the adenovirus type 12 (Ad12)-transformed cells induce tumors with high efficiency. Cells transformed with Ad2 preferentially attach to collagen type I and this attachment is enhanced by fibronectin. Highly tumorigenic Ad12-transformed cells attach less efficiently to collagen type I and their attachment ability is unaffected by fibronectin. These cells, however, strongly attach to type IV collagen and this attachment is considerably enhanced by laminin. Ad2-transformed cells attach less efficiently to collagen type IV and laminin has no effect on this process. The ability of adenovirus-transformed cells to degrade collagen also has been examined. The nontumorigenic cells secrete significant amounts of collagenolytic activity directed against type I collagen into the medium, but very little type IV collagenolytic activity is secreted. The highly tumorigenic cells secrete collagenolytic activity directed against both collagen types I and IV. In addition, their secreted type IV collagenolytic activity is significantly higher than that of the nontumorigenic cells. These results suggest that laminin mediated attachment to and degradation of type IV collagen may play a significant role in determining the tumorigenic and invasive potential of adenovirus-transformed cells.

Adenoviridae↗
PubMedDate not supplied

Permanent total parenteral nutrition: psychological and social responses of the early stages.

Permanent Total Parenteral Nutrition (TPN) is a life-saving but complicated procedure which has profound effects upon the lives of patients and their families, but there is a dearth of information on the the psychosocial consequences of this unique form of therapy. The authors worked with 19 consecutive TPN patients in hospital and after discharge and observed their reactions. It was found that the earliest stages were the most difficult, with anxiety, depression, fear, and negative body image predictable and universal experiences. Major adjustment problems centered around the loss of the basic function, eating. This artificial form of feeding forced multiple alterations in the patients' life styles. Their ability to cope with this intrusive procedure was related to the level of restitution of physical health, ego strength, and the family and hospital support systems. If, in addition to being a life-sustaining procedure, TPN is to restore the psychological stability of patients, all team members must be aware of the psychosocial factors involved.

Adaptation, Psychological↗