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B Sandler

Publications and source records attributed to B Sandler.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

A computed tomography-radiation therapy treatment planning system utilizing a whole body CT scanner.

An external beam radiation therapy treatment planning system has been developed to run on the GE CT/T whole body scanner. The system interactively obtains treatment planning information directly from CT scans, including relative density conversion of user input inhomogeneity regions. The program generates beams isodose tables from input TAR-SAR data using the Cunningham model. Inhomogeneity corrections are applied using the power law TAR method at low energies and the TAR ratio method at high energies. Beam data are generated on the central axis and at off-axis locations coplanar with each CT scan, and isodose distributions are displayed on any transverse, coronal or sagittal plane. Examples of plans and initial verification results are discussed.

Computers↗
PubMedDate not supplied

The immune response of rat spleen to dietary fibers and to low doses of carcinogen: morphometric and immunohistochemical studies.

The effects of high-fiber diets on anticancer immune response are often masked by the effects of high-dose carcinogens. Using low levels of carcinogen the splenic immune response can be evaluated. Colon tumors were induced in rats with low doses of 1, 2-dimethylhydrazine, in the following experimental groups: rats fed with low fiber diet without exposure to carcinogen; rats exposed to the carcinogen and fed with low-fiber diet; rats exposed to carcinogen, and maintained on high-fiber diets, and did not develop tumors; and rats that developed tumors after exposure to carcinogen and maintenance on either low-fiber or high-fiber diets. After 24 weeks their spleens were studied immunohistochemically and morphometrically. In tumor-free rats, low doses of carcinogen caused significant response of the lymphoid system. This was manifested in the intensive blast transformation and in an increase in the number of dendritic cells and macrophages in different structures of the spleen. Dietary fibers activated these processes: the number of Ki-67 positive cells, macrophages and plasma cells increased significantly in the red pulp. A positive correlation was found between the effects of the carcinogen and proliferation of lymphocytes in the white pulp, and to lesser degree between high-fiber diets and lymphocytic abundance in the red pulp. The number of splenic apoptotic lymphocytes decreased in rats exposed to carcinogen. In tumor-bearing rats, immune insufficiency of the splenic responses was seen in the significant decrease of the areas of the mantle layer and the periarterial sheaths, as result of the decreased number of lymphocytes. Dietary fibers reduced the degree of this insufficiency. Even low doses of carcinogen cause a significant splenic immune response. This reaction has a compensatory character with macrophages, B and T cells participating. Addition of any high-fiber diet after the exposure to carcinogen activated the lymphocyte proliferation in the spleen.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Tissue-specific expression of the p53 tumor-suppressor gene in the intestine of transgenic mice exposed to DMH and p53 antibodies.

We studied the tissue-specific expression of the p53 gene in different parts of the intestine of mice treated with low doses of a carcinogen and exposed to different p53 antibodies. The human p53 promoter-CAT transgenic mice were immunized with different p53 antibodies (monoclonal - PAb 421 and DO1, and polyclonal - H-p53 and anti-soluble p53 IgG) and then exposed to low doses of dimethylhydrazine (DMH). Enzymatic CAT activity was determined in the ileum and colon 8 weeks later after the final injection of DMH. Expression of the p53 transgene in the normal ileum was twice as high as in the colon. Treatment with DMH significantly decreased the expression of the p53 transgene both in the ileum (from 18% to 100%) and in the colon (from 10% to 52%). Vaccination of mice protected at least in part such a decrease. The most effective results were found after exposure of mice to polyclonal H-p53 and to a lesser extent to anti-p53 IgG. No difference was found in the effects of antibodies on the small and large intestines. We concluded that polyclonal antibodies were more effective than monoclonal ones in protection against anti-p53 action of DMH. The observation of these effects may make it possible to explain the higher antitumor activity of polyclonal antibodies.

Animals↗
PubMedDate not supplied

Transplacental tumor-preventive effects of polyclonal antibodies generated against the soluble 53 kDa antigen on mammary tumorigenesis in offspring.

This study was designed to determine whether immunizing females with polyclonal antibodies generated against the soluble 53 kDa tumor-associated antigen (s53 TAA) has a tumor-preventive effect on their progeny and whether this effect is manifested in some biochemical characteristics. Rat females were immunized before mating with anti-s53 IgG (50 microg/rat in Freund's complete and incomplete adjuvant, three times during a month) and their 5-week-old offspring was exposed to the carcinogen (dimethylbenz(a)antracene, 10 mg/rat). Results of these experiments were studied 4 months later. Vaccination of mothers decreased the tumorigenic effects of DMBA on their offspring. Blood levels of soluble TAA were analyzed in offspring of different groups. Two TAA were isolated from the blood, with molecular masses of 64 and 53 kDa. Their concentrations differed in offspring obtained from different maternal groups. Vaccination itself resulted in a marked increase in the blood levels of TAA, not only in the mothers but also in their offspring, however, this increase was not significant in tumor-bearing animals. In offspring from non-vaccinated mothers, tumorigenesis resulted in high overexpression of s53. In offspring from vaccinated mothers, a high blood level of s53 was shown even in tumor-free animals, probably due to maternal vaccination. We conclude that maternal vaccination before pregnancy increases immunoreactivity in offspring and can reduce risk of tumors in those progeny.

Animals↗
PubMedDate not supplied

Transplacental effects of a 15% olive-oil diet on chemically-induced tumorigenesis in offspring.

We evaluated whether feeding pregnant female rats a diet high in olive-oil, that showed a tumor-preventive effect in adults, has a similar preventive effect on chemically-induced cancer in offspring (i.e. mammary glands and colon cancer in rats). The control group was fed the same 7% corn-oil diet as their mothers. Experimental group I was fed a 7% corn-oil diet while their mothers received a 15% olive-oil diet. Experimental group II was fed the same 15% olive-oil diet as their mothers. Female offspring were twice administered 7,12-dimethylbenz(a)antracene (DMBA) in doses of 10 mg/rat. Male offspring were injected 6 times with 1, 2-dimethylhydrazine (DMH) in doses of 20 mg/kg body weight. Effect of DMBA was manifested in a high rate of tumorigenesis: the number of tumor-bearing rats in control offspring reached 52.0%. This effect increased to 60.6% among offspring of experimental group II and to 67.7% in offspring of experimental group I. The mean tumor size increased significantly in control offspring. Following administration of DMH number of tumor-bearing rats was similar in all groups of offspring: 36.7%, 40.7% and 42.8%. Tumor types differed: the majority of tumors in the control group were benign polyps and adenomas (72.1%) and the number of adenocarcinomas was low (27.9%). The number of malignant tumors increased to 37.5% in offspring of experimental group II and to 45.5% in offspring of experimental group I. In control group offspring, a distinct tendency to increased body weight and a significant increase in spleen weight were seen. The findings indicate that feeding mothers a diet high in fat concentrations, even those with known tumor preventive significance in adults, lose this cancer-inhibiting role in offspring.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

The role of blood levels of soluble 53 kDa protein and CEA in monitoring colon cancer patients.

BACKGROUND: The usefulness of determining blood levels of the soluble p53 antigen and CEA was evaluated with respect to the monitoring colon cancer patients. METHODS: HPLC (high performance liquid chromatography) was used to measure serum levels of the soluble 53 kDa protein (s53) after its partial isolation on gel fiberglass affinity chromatography columns. RESULTS: The blood of cancer patients before tumor removal contained a high amount of s53 protein which did not change significantly over several subsequent months (4.5 and 4.7 mg/ml, respectively). The average serum level of CEA was relatively low but with extremely high deviations (48 +/- 128 ng/ml). In patients with recurrent cancer and metastases, the serum concentrations of the s53 protein and CEA remained at high levels and their changes during the period studied were not significant (3.9 +/- 3.5 and 6.1 +/- 2.9 for s53; 56.5 +/- 148.5 and 209.9 +/- 867.3 for CEA). Disease progression was accompanied by slight increase in the serum levels of the s53 protein (3.5 +/- 2.2 and 7.6 +/- 4.6) or CEA (143.3 +/- 98.5 and 244.9 +/- 873.8). Despite the absence of statistically significant changes in the serum levels of the s53 protein in different groups of patients, on an individual basis such changes could be detected and could be of diagnostic value. CONCLUSIONS: Findings suggest that HPLC determinations of blood levels of the s53 protein can be a useful means of monitoring cancer patients only if tumor removal is complete and the patient exhibits a subsequent sharp decrease in the p53 protein serum level. In such cases, a following increase in the serum level of the p53 protein reflects the initiation of a new neoplastic formation which can then be detected a few months earlier than by any other available method. However, if the patient's immune system reacts weakly to the operation and the blood concentration of the s53 protein remains high, neither CEA nor s53 levels can be used for monitoring purposes.

Biomarkers, Tumor↗
PubMedDate not supplied

Vaccination with polyclonal non-tumor-specific IgG has no therapeutic effects on tumorigenic activity of hepatoma cells grafted to rats: experimental and biochemical studies.

BACKGROUND: We studied whether non-tumor-specific polyclonal IgG possesses antitumor effects on hepatoma tumor cells grafted to rats. METHODS: Hepatoma cells (5 x 10(5)-10(6)) were injected subcutaneously into 6-week-old rats. Some of the rats were vaccinated 2 months later with non-tumor-specific anti-R sheep IgG. Experimental results were checked after additional 2 months. RESULTS: The tumorigenic effect of grafted hepatoma cells was very high, manifesting itself in the rapid development of subcutaneous tumors in injected rats. Vaccination did not significantly change the number of tumors, their size or spleen weight. A biochemical study showed the main expression of two soluble proteins in high amounts in response to tumorigenesis, with molecular masses of 64 and 53 kDa. HPLC determination revealed that only the blood level of the soluble 53 kDa protein increased significantly with vaccination. CONCLUSIONS: Vaccination of rats with non-tumor-specific IgG had no tumor-therapeutic effects, despite the concomitant increase in the blood level of the soluble tumor-associated 53 kDa protein. Reaction of this protein should be considered non specific reflecting the host's reaction to stress.

Animals↗
PubMedDate not supplied

Response of the spleen of Balb/c and p53-transgenic mice to low doses of carcinogen and to polyclonal antibodies generated against the soluble 53 kDa protein.

BACKGROUND: We have previously reported that p53-transgenic mice are highly sensitive to low doses of a carcinogen and to vaccination with soluble 53 kDa antibodies, compared to normal mice. The splenic manifestation of this strain dependent hypersensitivity was investigated immunohistochemically and morphometrically. METHODS: The spleen was obtained from Balb/c and human p53 promoter-CAT transgenic mice. Mice had either been treated with the carcinogen dimethylhydrazine (DMH), vaccinated before DMH treatment with polyclonal IgG generated against the soluble 53 kDa protein, or left untreated. RESULTS: Significant differences in the splenic structures were found between the strains compared, including the area occupied by the white and red pulps, the periarterial lymphoid sheath (PALS) and the marginal zone, and in the number of lymphoblasts and lymphocytes. Exposure to DMH stimulated the immune response, but in transgenic mice the number of B and T lymphocytes and especially helper T lymphocytes was significantly lower than in Balb/c mice. Vaccination followed by DMH injections did not improve the insufficiency of the immune response in transgenic mice. In transgenic mice, the number of B lymphocytes in follicles was almost half and the total number of cells in PALS and the number of T lymphocytes were only 71% and 60% respectively in BALB/c mice. In the marginal zone, macrophages proliferated as lymphocytes decreased. CONCLUSIONS: Insufficiency of the immune system after exposure to a carcinogen is more pronounced in transgenic mice, and is mainly related to the B-cell system. It may stem from defects in B lymphocytes or from inherent differences in their maturation and regulation. The increase in the number of macrophages, dendritic cells and neutrophils illustrates the compensatory processes that can remedy this developing immune insufficiency.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Vaccination with soluble low-molecular weight tumor-associated proteins suppresses chemically-induced mammary tumorigenesis in rats.

This study attempted to elucidate whether the soluble tumour-associated proteins (TAA) of 66 kDa and 51 kDa molecular weight could suppress chemically induced mammary tumorigenesis. An intragastric dose of dimethylbenzanthracene (DMBA) was administered to rats and some were simultaneously immunised with the TAA. A single dose of DMBA resulted in 38% of the rats developing mammary tumours. However, simultaneous vaccination with the TAA preparation was significantly tumour-suppressive: mortality declined from 50% to 0% (p < 0.05); survival was extended from 9.4 weeks to 13.0 (p < 0.05), and 83% of the animals remained tumour free, compared to 13% of the control animals (p < 0.05). In 33% of the immunised animals the malignant tumours regressed completely. Such vaccination was also effective, although to a lesser extent, when the carcinogen dose was doubled. Then, 33% of the immunised and 22% of the control animals remained tumour-free, the latent period of malignant transformation was extended from 10.0 to 11.7 weeks, the initial tumour-free period lasted 9.3 weeks instead of 8.3 weeks and 10% survived compared to 50% of the controls. Vaccination with the soluble low molecular-weight TAA had distinct tumour-suppressive effects on mammary gland tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Controlled ovarian hyperstimulation for the new reproductive technologies.

The aim of controlled ovarian hyperstimulation (COH) is to induce multiple morphologically and functionally adequate follicles with the aim of harvesting multiple fertilizable oocytes. We compared several treatment regimens with different FSH/LH ratios: group I was the basic 2 human menopausal gonadotropins (2hMG) protocol in which 2 ampules of hMG were administered starting on day 3 of the cycle; group II was the basic 2hMG in which 2 ampules of "pure" follicle stimulating hormone (p-FSH) were added on day 3 and 4; group III was the 2 FSH protocol in which 2 ampules of p-FSH were administered beginning on day 3; finally, group IV was the 4FSH: 4 ampules of p-FSH on day 3 and 4 followed by 2 ampules of p-FSH daily. The reference regimen was the 2hMG. Except for the higher rate of immature oocytes in 2FSH and 2hMG protocols, the number of preovulatory oocytes and fertilization rate were similar in all protocols. No differences occurred in the pregnancy outcome. The low dose Lupron (LDL) stimulation was an experimental protocol applied to two groups of women who had previously failed COH. Eight women who had a premature luteinization and 8 women who showed a low response agreed to participate in the protocol. Ten micrograms of the GnRH agonist leuprolide acetate (Lupron) were injected subcutaneously every 6 hours starting on cycle day 2 and menotropin stimulation was begun on day 3-5, according to individual patient response. The LDL protocol was successful in determining a favourable estradiol pattern and fertilizable oocytes.

Drug Administration Schedule↗