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Biomedical subjects

A Zietman

Publications and source records attributed to A Zietman.

At least 19 recordsLinked to original sources
PubMed2001

The Patterns of Care Survey of radiation therapy in localized prostate cancer: similarities between the practice nationally and in minority-rich areas.

PURPOSE: Over the last two decades, the chance for the cure of localized prostate cancer by radiation has been improved by the widespread use of PSA for early detection and by a number of technical advances in treatment delivery. This study was designed to determine whether the stage of presentation and the quality of radiation treatment delivered are comparable between Caucasian and minority patients nationally and within minority-rich areas. METHODS AND MATERIALS: A random survey conducted for the Patterns of Care Study in Radiation Oncology of 80 facilities treating patients with radiation in the USA. Of these, 67 comprise the "National Survey" and 13 a "Minority-Rich" survey (>40% of treated patients are minorities). Nine hundred twenty-six men with localized prostate cancer were treated in 1994. Five hundred ninety-five were in the national and 331 in the minority-rich survey. The main outcome measures were the clinical features of Caucasian and minority men at presentation and technical characteristics of the treatment delivered to them. RESULTS: African-American men presented with more advanced disease (higher-presenting PSA and T-stage) than Caucasians in both the national and the minority-rich surveys. Hispanics also presented with later disease and could be grouped with African-American men rather than Caucasians. Overall the stage and PSA at presentation was earlier than seen in the previous Patterns of Care Study survey of 1989. The quality of treatment delivered has improved since 1989, with no distinction seen between those facilities sampled nationally and those within minority-rich areas. CONCLUSION: African-American and Hispanic men with prostate cancer present for therapy at a later stage than Caucasian men, but when they do, the treatment received is of comparable quality.

Black or African American↗
PubMed2000

Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localized prostate cancer.

CONTEXT: Multiple treatment options are available for men with prostate cancer, but therapeutic recommendations may differ depending on the type of specialist they consult. OBJECTIVE: To define and contrast the distribution of management recommendations by urologists and radiation oncologists for a spectrum of men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Mail survey sent in 1998 to a random sample of physicians in the United States, who were listed as urologists (response rate 64%, n=504) and radiation oncologists (response rate 76%, n=559) in the American Medical Association Registry of Physicians and practicing at least 20 hours per week. MAIN OUTCOME MEASURE: Questionnaire addressing beliefs and practices regarding prostate cancer management. RESULTS: Forty-three percent of radiation oncologists vs 16% of urologists would recommend routine prostate-specific antigen testing for men aged 80 years and older. For men with moderately differentiated, clinically localized cancers, and a more than 10-year life expectancy, 93% of urologists chose radical prostatectomy as the preferred treatment option, while 72% of radiation oncologists believed surgery and external beam radiotherapy were equivalent treatments. For most tumor grades and prostate-specific antigen levels, both specialty groups were significantly more likely to recommend the treatment in their specialty than the other treatment. Both groups reported giving patients similar estimates of the risks of complications due to surgery and radiation. Neither group favored watchful waiting in their treatment management except for a subset of men with life expectancies of less than 10 years and cancers with very favorable prognoses (Gleason score of 3 or 4 and prostate-specific antigen level </=5 ng/mL). CONCLUSIONS: Based on this study, while urologists and radiation oncologists do agree on a variety of issues regarding detection and treatment of prostate cancer, specialists overwhelmingly recommend the therapy that they themselves deliver. JAMA. 2000;283:3217-3222

Adult↗
PubMed1998

Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease.

Loss of heterozygosity (LOH) at chromosome 11q23 has been found in a variety of epithelial human neoplasms, suggesting that this region contains a tumor suppressor gene(s) important to tumorigenesis. We investigated whether LOH at 11q23 could be detected in squamous cell carcinoma of the head and neck (SCCHN), and whether loss at this site was associated with specific clinical parameters. Fifty-six matched blood and SCCHN tumor samples taken at the time of diagnosis were evaluated for LOH at three microsatellite markers at 11q23. Multiplex PCRs with [alpha-32P]dCTP labeling of the amplified DNA strands were performed. Clinical data were obtained from medical record review. LOH at 11q23 was found in 13 of 52 (25%) evaluable tumors. There was no association between LOH at 11q23 and amplification of the CCND1 (cyclin D1) oncogene or inactivation of the p53 gene, which had been determined previously. With a mean follow-up of 24 months, an association independent of tumor size or stage was found between LOH at 11q23 and recurrent disease (P = 0.04). Among subjects who received radiotherapy (RT) as a component of their treatment, LOH at 11q23 was associated with persistent or recurrent locoregional disease (P = 0.05). LOH at 11q23 occurs in a subset of SCCHN. It is associated with a higher likelihood of recurrent disease, perhaps related to resistance to RT. The specific gene(s) and mechanism(s) responsible remain to be identified. Until then, LOH at 11q23 might become a marker identifying patients likely to do poorly with conventional therapy.

Carcinoma, Squamous Cell↗
PubMed1994

Multivariate determinants of radiocurability. I: Prediction of single fraction tumor control doses.

PURPOSE: The relationship between various laboratory determinants of radiocurability considered alone and in combination, and the observed 50% tumor control dose, has been examined in rodent and xenografted human tumors. METHODS AND MATERIALS: The single fraction 50% tumor control dose (TCD50) under normal and clamp hypoxic conditions, 50% tumor cell transplant dose (Td50), and in vitro estimated tumor cell radiosensitivity parameters, were determined in each of six tumor types (four isografted murine and two xenografted human tumors). Subcutaneous transplant sites and identical or similar tumor generations were used for both the Td50 and TCD50 studies. Radiosensitivity parameters were obtained using the clonogenic assay, after allowing cells to enter the active growth phase to recover from trypsin induced alterations of cell radiosensitivity. Both control and irradiated cells were multiplicity corrected. RESULTS: No single parameter (InTd50, hypoxic fraction, or intrinsic radiosensitivity) correlated with the observed tumor control doses under aerobic or hypoxic conditions. However, when considered in combination, clonogenic fraction (estimated by Td50(-1)), and intrinsic radiosensitivity, predicted the rank-order of tumor control doses with a significant degree of accuracy, and tumor hypoxia influenced the value of the control dose. All parameters were demonstrated to be significant determinants of radiocurability, with substantial tumor to tumor variation in the relative importance of each. For the six tumor types, the combined laboratory determinants predicted 50% tumor control doses which differed from the observed TCD50s by an average of approximately 9 Gy under hypoxic conditions. CONCLUSION: The results obtained demonstrate: (a) the necessity of simultaneously considering all determinants of radiocurability if the role of a single determinant is to be assessed; (b) laboratory determinants may accurately predict tumor radiocurability.

Animals↗
PubMed1994

Malignant lymphoma of the testis, epididymis, and spermatic cord. A clinicopathologic study of 69 cases with immunophenotypic analysis.

We studied 69 cases of malignant lymphoma of the testis, epididymis, and spermatic cord, including 64 cases in which the tumor involved these sites at presentation and five cases in which lymphoma relapsed in the testis. The patients without prior lymphoma were 16 to 91 (mean, 56) years old. Fifty-two patients had diffuse large-cell lymphomas [seven large cleaved cell (two with follicular areas), 27 large noncleaved, two multilobated, six not otherwise specified (NOS), 10 immunoblastic]; six, small noncleaved cell; two, diffuse mixed small and large cell; one, diffuse small cleaved; one, follicular mixed small cleaved and large cell; and two, high grade, unclassified in the Working Formulation. Twenty-nine cases (55%) were stage I; five (9%), stage II; one (2%), stage III, and 18 (34%), stage IV. Forty patients (73%) achieved a complete remission; 23 had a relapse of tumor at 4 to 274 months (median, 13) and five were salvaged. At last follow-up, 20 (36%) patients were free of disease, six (11%) were alive with disease, and 29 (53%) had died of lymphoma. Features associated with longer disease-free actuarial survival (DFS) included stage I disease (p = 0.0001) and sclerosis (p = 0.0001). Among patients with stage I lymphoma, those with right-sided tumors (p = 0.005) or tumors with sclerosis (p = 0.0017) had longer DFS. Lymphomas with extensive sclerosis were all stage I (p = 0.0057). Four of five patients with secondary testicular lymphoma had extranodal primary sites. They ranged from 13 to 66 years (median, 35). Testicular relapses occurred 13-37 months after initial diagnosis. Three had diffuse large, noncleaved cell type; one, lymphoblastic and one, diffuse mixed small and large cell. Immunophenotyping showed B lineage in 33 cases and T lineage in one case. Most testicular lymphomas are B-lineage large-cell lymphomas, which frequently involve other extranodal sites at presentation and at relapse, and which often have an aggressive clinical course.

Adolescent↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.

Animals↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the brain of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993) that the take rate of human xenografts in the s.c. tissue of severe combined immunodeficient (SCID) mice is significantly higher than that of nude mice. Earlier, this laboratory reported that the transplantability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of human and murine tumors in comparison with s.c. tissue in SCID mice; (b) the relative i.c. transplantability in SCID mice in comparison to nude mice; and (c) the influence of whole-body irradiation on i.c. transplantability of SCID and nude mice. The assay based on the number of cells required to transplant tumors into 50% of recipients (TD50) was used to describe the transplantability assays. Five human and four murine tumor cell lines were used. Concurrent TD50 assays were performed i.c. in whole-body irradiated and nonirradiated SCID and nude mice. Serial 2-10-fold dilutions of cells were injected in a 10-microliters volume into the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50S were significantly lower than the s.c. TD50S by a factor of 1.7-1580. The average enhancement ratio (s.c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No significant difference was found between the i.c. TD50S in SCID and in nude mice, contrary to the significant difference in s.c. TD50S between both strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID mice. In conclusion, despite the significantly lower s.c. TD50S of human xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immunoreactivities between nude and SCID mice in s.c. transplantability; however, for i.c. transplantability, nude mice behaved equally as well as SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immunoreactivity, although the immunoreactivity is significantly lower than that of nude mice.

Animals↗
PubMed1990

Lack of efficacy of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma for the detection of malignant tumors.

Water-suppressed proton nuclear magnetic resonance (NMR) spectroscopy of plasma has been proposed by Fossel et al. (N Engl J Med 1986; 315:1369-76) as a technique for detecting malignant tumors. In their analysis, plasma samples from patients with cancer were clearly distinguished from those of normal subjects by measuring and averaging the methyl and methylene line widths of plasma lipoproteins in NMR spectrums. To evaluate this diagnostic procedure further, we collected and analyzed by NMR spectroscopy 145 samples of plasma from patients who served as controls, most of whom were undergoing orthopedic or cardiac surgery (n = 66); patients with a variety of untreated malignant tumors (n = 25) or treated malignant tumors (n = 18); and patients with hyperplastic or "premalignant" diseases, such as benign prostatic hyperplasia and ulcerative colitis (n = 36). All the samples were coded, and NMR spectroscopy was performed without knowledge of the patients' clinical status. There were no significant differences in the NMR line widths among the four study groups (P greater than 0.05 for all pairwise comparisons). The specificity and sensitivity of this method for distinguishing the control patients (mean line width [+/- SD], 44.0 +/- 7.4 Hz) from those with untreated cancer (43.8 +/- 6.9 Hz) were poor, with a false positive rate of 52 percent (34 of 66) and a false negative rate of 56 percent (14 of 25). Inverse correlations of line widths with age (P less than 0.01) and with the plasma triglyceride level (P less than 0.001) were detected. We conclude that NMR spectroscopy of plasma is not an accurate test for the detection of malignant tumors.

False Negative Reactions↗
PubMed1990

Radiation response of xenografts of a human squamous cell carcinoma and a glioblastoma multiforme: a progress report.

Human cell lines derived from squamous cell carcinomas of the pharynx (FaDu and HSCC6) and glioblastoma multiforme (U87, A2, A7, MMC-1, MMC-2) have been studied in vitro as monolayers in exponential (all 7 cell lines) or plateau phase (FaDu and U87), and as 1 mm diameter spheroids in vitro (FaDu and U87) and as 6 mm diameter xenografts growing in the legs of athymic NCr(nu/nu) nude mice (FaDu, HSCC6, U87, A7 cells). For SF2s and D values, there was broad overlap of values between SCC and glioma cell lines. In contrast, the D0 values were higher for U87, A2, A7, and MCC-1 than the two SCC cell lines, while the extrapolation numbers were greater for the two SCC lines than any of the glial tumor lines (these differences were not regularly significant). Complete dose response assays for local control of FaDu, HSCC6, U87, and A7 xenografts have been performed under conditions of normal blood flow and clamp hypoxia for tumors growing in mice which had received 6 Gy WBI at 24 hr before transplantation. Under the latter circumstances, irradiations have been performed on FaDu and U87 as single doses or as 2, 4, or 8 equal doses; for the fractionated irradiation, treatments were given on a BID basis with 4 hr between the treatments on any 1 day. For irradiation of 1 mm diameter spheroids, radiation was administered as single doses under conditions of equilibration with AIR. The TCD50 for the FaDu was significantly higher and the dose response curve steeper for tumors growing in immune suppressed (6 Gy WBI 24 hr prior to transplantation) than in control nude mice. Tumors, exponential or plateau phase cells, and spheroids derived from U87 were significantly and substantially more resistant under all conditions and fractionation schedules than for FaDu. Thus, the in vitro results do not indicate a clearly greater resistance by the glioma cell lines, while the more limited TCD50 data (single dose and 8 fractions irradiation) show more resistance in vivo by the glial tumors. We noted that the TCD50 values for U87 and A7 glial tumors overlap those for spontaneous tumors of the C3H mouse but are higher than the human squamous cell carcinoma xenografts in the nude mice. Substantial additional data from xenografts are needed to determine if the higher TCD50 values for GBMs, especially for fractionated irradiation, is a regular finding and is of sufficient magnitude to be pursued by studies to explain the observed differences.

Animals↗
PubMed1990

Fractionation sensitivity and immunological status in radiation treated murine sarcomas.

The fractionation sensitivity of a strongly immunogenic murine fibrosarcoma (FSa1) was tested in highly immunosuppressed (18 Gy whole body irradiation, 10 fractions, 4 days and bone marrow salvage) and control mice (C3Hf/Sed). Radiation was delivered to extremity-transplanted tumors after reaching a volume of 250 mm3. Two, 4 and 10 fractions were used, delivering the radiation treatments to uniformly hypoxic tumors (by extremity clamping). Doses needed to attain a 10 day tumor-growth delay (TGD) over the volume range 250 mm3 to 1000 mm3, and doses necessary to reach a tumor-control probability of 50% (TCD50), were calculated for the three fractionation schedules. Immunosuppression influenced the TCD50 values profoundly: 56.2, 71.5, and 101.4 Gy in control mice versus 76.6, 104.2, and 141.1 Gy in immunosuppressed mice for 2, 4, and 10 fractions, respectively. The alpha/beta ratios estimated by reciprocal-dose analysis using the TGD and TCD50 assays were not significantly different, nor were the alpha/beta ratios of tumors grown in immunosuppressed mice (TGD 5.7 Gy; TCD50 5.3 Gy) as compared with tumors in control recipients (TGD 3.5 Gy; TCD50 4.9 Gy). In addition, direct analysis was used with the fractionated TCD50 data from control and immunosuppressed animals to calculate a immunity-related-cell-kill factor. For 250 mm3 tumors a 1.29 [0.99 . . . 1.59, 95% confidence interval] log10-kill factor was obtained.

Animals↗
PubMed1990

Failure of 1H nuclear magnetic resonance spectroscopy of blood plasma to detect malignancy.

Water-suppressed proton nuclear magnetic resonance (NMR) of plasma was proposed as a technique for detecting malignant tumors. In that analysis, bloods drawn from cancer patients at the Beth Israel Hospital (BIH; Boston, MA), were easily distinguished from normal subjects by measuring and averaging the proton NMR methyl and methylene line widths of plasma lipoproteins. We collected blood at the Massachusetts General Hospital (MGH), including from normal controls, patients with untreated and treated malignant tumors, and patients with nontumor diseases. The plasma NMR analyses were carried out blind. The code was not broken until all patient charts and pathology records were reviewed, plasma analyses were completed, and patients had been divided into appropriate clinical groups. Analysis of these data showed no differences between the means of the study groups (false-positive and false-negative frequencies 46% and 57%, respectively). An inverse correlation of methyl/methylene line widths with age (P less than .01), and a correlation with nitrate-requiring cardiovascular disease (P less than .05) was, however, evident. This test cannot be validly used to detect malignancy.

Adult↗
PubMed1989

Comparative morphometric study of tumor vasculature in human squamous cell carcinomas and their xenotransplants in athymic nude mice.

When human tumor xenotransplants into nude mice are used as experimental models, it is important to know whether their microvascular anatomy is rather host or tumor specific. Therefore a morphometric comparison of the vascular network in human squamous cell carcinomas and their xenotransplants was carried out. Biopsies were taken from surgical specimens of three squamous cell carcinomas of the oral cavity. Part of the material was processed for histology and the rest was cut into 1-mm3 cubes and transplanted s.c. into the lateral thorax of athymic nude mice [NCr/Sed(nu/nu)]. The microvascular architecture of original tumors and of three first, one second, and one late generation xenografts was compared. Capillaries were identified in original human tumors by anti-factor VIII staining and in xenografts with antilaminin staining. The median distances between interphase tumor cells and blood vessels were determined and were found to be much longer in original human tumors than in xenografts, ranging from 81 microns to 99 microns and 53 microns to 65 microns, respectively. However, the characteristic qualitative histology of tumors appeared to be preserved in xenotransplants. Analysis of the topographic distribution of mitotic figures revealed that in both original tumors and xenotransplants proliferation of tumor cells was concentrated around blood vessels. Again, vascular distances in original tumors were significantly longer than in xenotransplants. In addition, xenotransplants into nude mice from a long passaged cell line from a human pharyngeal squamous cell carcinoma, FaDu, was investigated. FaDu showed a rare-fication of the capillary network with increasing tumor volume, but a constant median distance of mitotic figures from blood vessels. In conclusion, the pattern of spatial distribution of proliferating tumor cells as well as differentiation characteristics appear to be retained in xenograft tumors, but the density of the vascular system is host specific. This has to be taken into account when physiological parameters of blood supply are studied in xenotransplanted tumors.

Animals↗
PubMed1989

The growth and cell kinetics of a secondary tumor after radiation or surgical treatment of the primary tumor.

Early transplants of a spontaneous mouse fibrosarcoma (FSa II) were used to investigate whether radiation or surgical treatment of a tumor in the leg altered the growth or cell kinetics of a second tumor in the axilla. The volume doubling times and in vivo Bromodeoxyuridine labeling indices of the axillary tumors were the same in the control group and in the groups which received 70 Gy to the leg tumor or normal leg. After surgical removal of the leg tumor, there was small reduction in the time to reach 1500 mm3 (4.0 vs 4.6 days) and an increase in Bromo-deoxyuridine labeling index at Day 3 (18% to 24%) in the axillary tumors. In all groups, there was a fall in labeling index with time reflecting increasing tumor size.

Animals↗