The formation of variants with a reversion of properties of transformed cells. 3. Reversion of the structure of the cell surface membrane

The cell surface structure of variants from polyoma-transformed cells grown in animals and then cultured in vitro, which show a reversion of in vitro properties of transformation without losing the ability to synthesize the polyoma-specific nuclear tumor (T) antigen, has been studied by using the carbohydrate-binding protein concanavalin A (Con. A) which interacts with sites on the cell surface membrane. Transformed cells are agglutinated by this protein. Normal cells, whose sites for Con. A are mainly in a cryptic form, are agglutinated only after they have been treated with trypsin. It has been shown that some variants showed a partial, and others a complete, loss of agglutinability by Con. A, and that the agglutinability of these variants was restored by treatment with trypsin. Compared to the parental transformed cells, all the variants showed the same decrease in cloning efficiency in fluid medium and soft agar, and in saturation density. The results indicate that the surface structure of transformed cells can completely revert to the structure found in normal cells, as measured by reversion to the cryptic form of sites for Con. A; that the synthesis of T antigen, presumably due to integrated virus DNA, is by itself not sufficient to prevent this reversion; that variants with this reversion in cells grown in vitro can have a high degree of tumorigenicity in animals; and that a threshold for the number of exposed surface sites for Con. A has to be exceeded before the cells express the in vitro properties of transformation.     

A possible role for IVIg in the treatment of soft tissue sarcoma: a clinical case and an experimental model

A patient with a malignant peripheral nerve sheath tumor (MPNST) was treated with IVIg for multiple sclerosis. Her MPNST course was remarkably longer and more indolent than expected; she achieved a disease-free interval (DFI) of 30 months. Seven other patients, who were not treated by IVIg, had a relatively aggressive course (median DFI 3 months). These results led us to examine the effect of IVIg on the growth of sarcoma in vitro and in vivo in an experimental model of MCA-bearing mice. When added to MCA-105 sarcoma cell cultures, IVIg produced a dose-dependent inhibitory effect on [(3)H]-thymidine incorporation. The maximal inhibitory effect was at a concentration of 50 mg/ml IVIg. Cell cycle analysis revealed a hypodiploid peak at the lower fluorescence values which appeared in the samples treated with IVIg. These results demonstrate that the anti-proliferative activity results from an apoptotic effect of IVIg on the tumor cells. In a second set of experiments, we evaluated the capability of IVIg, when administered orally or subcutaneously, to inhibit the growth of MCA-105 sarcoma lung metastases. A decrease in the mean lung weight was observed in the mice that were treated by s.c. or oral administration, the latter being more effective. A possible role for IVIg in the treatment of MPNST and other soft tissue sarcomas is suggested.     

Is forequarter amputation justified for palliation of intractable cancer symptoms?

BACKGROUND: Limb-sparing surgery has replaced the radical surgical approach for treating limb sarcomas in most cases. Amputation has been advocated as a palliative procedure for symptomatic locally advanced disease that has already failed to respond to radiation therapy, chemotherapy and limited surgery. METHODS: Twelve patients with advanced malignant tumors involving the shoulder girdle or the proximal humerus underwent forequarter amputation (FQA) for palliative purposes. The tumor-related local problems were severe pain, limb dysfunction, tumor fungation, bleeding (requiring emergency FQA in one case) and infection. The preoperative Karnofsky performance status (KPS) in our series ranged from 30 to 70%. RESULTS: No perioperative mortality was observed. The morbidity was well tolerated by the patients. The KPS improved in most of the patients, and was assessed as 90-100% in 9 of the 12 patients. Overall, quality of life was reported to be at least moderately improved by 2 out of 3 patients. Survival was measured in months (3-24 months), but ultimately had no meaning since the procedure was palliative. Lung metastases were the dominant cause of death in our patients. CONCLUSIONS: The results of FQA in our series point to its feasibility and the gain in quality of life and performance status in severely ill patients with advanced malignancies. Local symptoms and signs were controlled, and quality of life was restored.     

Effects of percutaneous transluminal coronary angioplasty on cardiopulmonary responses during exercise

AIM: The aim of this study was to examine by means of percutaneous transluminal coronary angioplasty (PTCA) whether dilating blocked coronary arteries in patients with coronary heart disease will improve relevant attributes measured during cardiopulmonary exercise testing (CPET). METHODS: Fourteen myocardial ischemia patients (13 male, 1 female; age range: 42-72 years), who were referred for cardiac catheterization, participated in the study. Eight patients underwent PTCA (experimental group) and 6 did not (control group). All subjects performed CPET about 2 weeks before and 3 weeks after cardiac catheterization. RESULTS: The results of electrocardiogram (ECG) analysis reveal a very low predictive accuracy (36%) for identifying coronary heart disease and/or anatomical changes caused by the PTCA. However, selected CPET parameters in the experimental group only showed significant post-PTCA changes from baseline. Peak oxygen uptake (VO(2)) increased from 17.49 to 20.75 mL x kg(1) x min(1), ventilatory anaerobic threshold from 12.15 to 14.39 mL x kg(1) x min(1), peak oxygen pulse (O(2)pulse) from 11.76 to 13.27 mL x beat(1), and O(2)pulse slope from 7.05 to 9.25, slope category. No significant inter- or intra-group differences were found in peak exercise heart rate, respiratory exchange ratio, subjective rating of perceived exertion, or systolic and diastolic blood pressure. CONCLUSIONS: This study suggests that selected CPET parameters seem to be highly sensitive to changes in cardiac function caused by the PTCA, significantly more than with conventional stress ECG. These findings merit further investigation.     

The effect of calcium intake and physical activity on bone quantitative ultrasound measurements in children: a pilot study

Environmental factors, such as nutritional status, physical activity, and drug therapy, can affect bone mineralization. Our objective was to evaluate the relationship between nutritional status, physical activity, and bone mineralization as assessed by multisite quantitative ultrasound technology in children. The study group comprised 67 children, aged 6–17 years (mean, 9.4), attending a primary care clinic. Data on calcium intake and physical activity were collected using a detailed questionnaire. Speed of sound measurements were performed at the distal 1/3 radius and the midshaft tibia using Sunlight Omnisense apparatus. The reported mean calcium intake was 1105 mg/day. There was a significant difference in Z-scores at the radius and tibia between the low-and high-calcium-intake groups (P = 0.004, P = 0.035, respectively). A similar difference was found between the low-and normal-physical-activity groups (P = 0.015, P = 0.036, respectively). In this pilot study, a positive association was found between calcium intake, physical activity, and bone status, as assessed by the quantitative ultrasound technique.     

Adjuvant treatment of high-risk stage II breast cancer with doxorubicin followed by high-dose chemotherapy and autologous stem-cell transplantation: a single-institution experience with 132 consecutive patients

Several studies have shown conflicting results with the use of intensive consolidation chemotherapy for breast cancer. The aim of the present study was to investigate the efficacy, feasibility and toxicity of high-dose chemotherapy with stem cell support in patients with high-risk stage II breast cancer. From February 1994 to November 1998, 132 consecutive patients with multinode positive breast cancer were entered to the study. In total, 86 patients had >or=10 positive axillary lymph nodes, and 46 had 4-9 positive axillary lymph nodes with at least two additional predetermined risk factors at diagnosis. All patients were offered adjuvant chemotherapy (doxorubicin, 75 mg/m(2) x 4) followed by high-dose chemotherapy (cyclophosphamide 6000 mg/m(2), carboplatin 800 mg/m(2) and thio-tepa 500 mg/m(2)) and autologous stem cell support with growth factor. In all, 131 patients also received local radiation therapy and tamoxifen based on receptor status. After a median follow-up of 51 months (range 27-87), the disease-free and overall survival rates were 72 and 81%, respectively. There was no difference in the outcome for high-risk patients with > or < than 10 positive axillary lymph nodes. On Cox regression analysis only progesterone receptor status was predictive of disease-free, but not overall survival. There were no treatment-related deaths; grades III-IV toxicity was relatively low. This combined approach of doxorubicin followed by high-dose chemotherapy and stem-cell support, followed by locoregional radiotherapy, was safe and seems to be effective in patients with multinode positive stage II breast cancer. In previous trials of adjuvant high-dose therapy in this patient population, treatment-related morbidity and mortality markedly influenced the outcome. For this high-risk patient population, further testing of intensive chemotherapy regimens with a lower toxicity profile is warranted.     

Clinical improvement and shrinkage of uterine fibroids after thermal ablation by magnetic resonance-guided focused ultrasound surgery.

OBJECTIVE: Hysterectomy or myomectomy are the accepted treatments for symptomatic uterine fibroids. Heat ablation of uterine fibroids has been shown to be an effective alternative treatment. The aim of this study was to determine the clinical efficacy of non-invasive thermal ablation by transcutaneous magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) for the treatment of symptomatic uterine fibroids. METHODS: In this prospective study, MRgFUS ablation of uterine fibroids was performed in 35 symptomatic women scheduled for hysterectomy. Clinical symptoms, patient satisfaction and uterine size were determined at 1 month and 6 months after the procedure. RESULTS: This outpatient procedure was very well tolerated by all women. Sixty-nine percent (24/35) of the treated patients reported either significant or partial improvement in symptoms. Treated fibroids decreased in volume by 12% and 15% at 1 and 6 months, respectively. Minor transient side-effects were observed in two women. Six women underwent hysterectomy during the follow-up period. CONCLUSION: This study demonstrates the clinical efficacy of MRgFUS ablation of uterine fibroids. This novel, non-invasive surgical approach may offer an alternative therapy for women with uterine fibroids.     

Detecting nanoparticles in tissue using an optical iterative technique

Determining the physical penetration depth of nanoparticles (NPs) into tissues is a challenge that many researchers have been facing in recent years. This paper presents a new noninvasive method for detecting NPs in tissue using an optical iterative technique based on the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient (µ_s''), of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. Presented in this paper are the results of a tissue simulation which indicate a linear ratio between the STD and the scattering components. A linear ratio was also observed in the tissue-like phantoms and in ex vivo experiments with and without NPs (Gold nanorods and nano Methylene Blue). The proposed technique is the first step towards determining the physical penetration depth of NPs.OCIS codes: (160.4236) Nanomaterials, (120.5820) Scattering measurements, (190.4710) Optical nonlinearities in organic materials