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S Kramer

Publications and source records attributed to S Kramer.

At least 19 recordsLinked to original sources
PubMed1992

Pediatric craniopharyngiomas: long term results of combined treatment with surgery and radiation.

From 1961 to 1981, 19 pediatric patients with craniopharyngiomas were treated with external beam radiation post surgery. Twelve underwent primary treatment while seven were treated for recurrence. Median follow-up is 21 years (range 8-28 years) with an overall 20-year survival of 62%. Twenty-six percent (5/19) developed disease recurrence following radiation. Of the multiple patient and treatment parameters analyzed, only initial disease status (i.e., primary vs recurrence), surgical extent, radiation dose, and treatment prior to routine use of CT scans (1961-1974) appeared to have major influence on patient outcome. The 20-year survival for those treated for primary disease was 78% versus 25% for those treated for recurrence. Fifty percent (3/6) of patients receiving tumor doses of < or = 5400 cGy developed recurrences versus 15% (2/13) in those receiving > 5400 cGy. Four of the five recurrences occurred in patients treated during the pre-CT era. Long term effects of treatment were analyzed. Surgical morbidity correlated strongly with extent of surgery. All patients who underwent total resection developed surgical sequelae. Radiation morbidity correlated strongly with radiation dose. The incidence of vascular or neurologic complications attributable to radiation were minimal, occurring in only two patients. Both received doses higher than that given with modern therapy. Long-term results from this series are better than those reported with surgery alone. Use of modern surgical and radiation equipment/technique along with CT/MRI imaging should yield improved treatment results both in terms of lower recurrence and lower toxicity rates.

Adolescent↗
PubMed1991

Effects of pancreastatin (24-49) on growth of normal pancreas and pancreatic cancer.

In the present study, the effects of pancreastatin on growth are evaluated in two human pancreatic cancer cell lines, in vivo and in vitro, and on athymic nude mouse pancreas. SW-1990 and MIA PaCa-2 pancreatic cancer cell lines were grown in serum-supplemented and serum-free medium in the presence of pancreastatin (10(-11)-10(-6) M), or cholecystokinin (CCK) (10(-11)-10(-8) M) or combinations thereof. Growth was evaluated by [3H]thymidine incorporation and cell counts. Pancreastatin significantly inhibited DNA synthesis in both cell lines, and cell counts in SW-1990 on days 3 and 5 but not 7. CCK-stimulated cell growth was inhibited in both cell lines and mouse pancreas by pancreastatin. Pancreastatin had no effect in the presence of fetal bovine serum. In the in vivo experiments, pancreastatin (15 micrograms/kg) did not affect growth of SW-1990 xenografts to nude mice, but inhibited CCK-stimulated growth transiently. Pancreastatin (100 micrograms/kg) transiently decreased volumes of MIA PaCa-2 xenografts to nude mice and significantly decreased weight, protein, and DNA of mouse pancreas. Fasting glucose levels of mice treated with pancreastatin 100 micrograms/kg for 35 days were significantly lower than controls. Our results demonstrate that pancreastatin not only inhibits CCK-stimulated pancreatic growth but also has inhibitory effects by itself.

Animals↗
PubMed1991

Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung.

In the context of the central role of the alveolar macrophage in host defense of the respiratory epithelial surface, and the ability of IFN-gamma to activate mononuclear phagocytes, we have evaluated strategies to use rIFN-gamma to activate human alveolar macrophages in vivo. To accomplish this, rIFN-gamma was administered to nonsmoking normals, the amounts of IFN-gamma quantified in serum and respiratory epithelial lining fluid (ELF) and the status of IFN-gamma related activation of blood monocytes and alveolar macrophages was evaluated by quantifying the expression of mRNA transcripts of IP-10, a gene induced specifically by IFN-gamma. Systemic administration (subcutaneous) of maximally tolerated amounts of rIFN-gamma (250 micrograms) was followed by detectable levels of IFN-gamma in serum but not ELF, the expression of IP-10 transcripts in blood monocytes but not alveolar macrophages, and multiple systemic adverse effects. To circumvent the inability of systemic administration to reach respiratory ELF and activate alveolar macrophages, rIFN-gamma (250-1,000 micrograms) was inhaled as an aerosol once daily for 3 d. Strikingly, while IFN-gamma was not detected in serum it was detectable in respiratory ELF in a dose-dependent fashion. Further, alveolar macrophages, but not blood monocytes, expressed IP-10 mRNA transcripts and, importantly, inhalation of aerosolized rIFN-gamma was not associated with local or systemic adverse effects. Thus, it is feasible to use rIFN-gamma to activate alveolar macrophages by targeting the cytokine directly to the lung. These data suggest a potential strategy for targeted cytokine therapy, without systemic side effects, to augment respiratory tract defenses in individuals at risk for or with lung infection.

Actins↗
PubMed1991

Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues.

Monoclonal and polyclonal antibodies recognizing human parathyroid hormone-like protein (PTHLP) have been produced using a series of recombinant and synthetic PTHLP peptides. These antibodies have been used to develop a two-site immunometric enzyme immunoassay which detects PTHLP[1-87] and PTHLP[1-141] but not PTH. The immunoassay detected PTHLP in extracts of squamous carcinomas and normal tissues at concentrations from 7-515 ng PTHLP[1-87]/mg protein. Immunoblotting of the extract which showed the highest immunoreactivity, a squamous carcinoma of the lung from a patient with hypercalcemia, revealed a major band having an apparent mol wt of 26,500 and several other higher mol wt bands. Similar polypeptides were observed by immunoblotting cell extracts from a cell line, SCaBER, which secretes immunoreactive PTHLP into its medium and also from tumors in nude mice derived from this cell line. Chaotropic agents did not alter the immunoblotting pattern, and antibodies to three different epitopes of PTHLP recognized these bands, indicating PTHLP expression in the extracts. Immunohistochemical staining of normal human tissue with these antibodies revealed several PTHLP-containing tissues and confirmed the results of the immunoassay, suggesting a paracrine role for PTHLP. Staining was observed in several neoplastic tissues including squamous cell carcinomas, lung carcinoma, bladder carcinoma, osteogenic sarcoma, and adenocarcinoma of the colon.

Adenocarcinoma↗
PubMed1991

Expression of neu protein, epidermal growth factor receptor, and transforming growth factor alpha in breast cancer. Correlation with clinicopathologic parameters.

The major objectives of this study were twofold: to determine 1) if growth factors or growth factor receptors were expressed similarly or differently in a clinically well-characterized group of breast cancer patients and 2) if these phenotypic characteristics were associated with any of the commonly used prognostic parameters. Formalin-fixed paraffin-embedded tumor tissue from 51 node-positive breast cancer patients were analyzed for the expression of neu, epidermal growth factor-receptor (EGF-R), and transforming growth factor alpha (TGF alpha) using immunoperoxidase staining. Positive membranous staining for neu was observed in 15 (29%) tumors. Over-expression of neu was observed in high-grade, estrogen-receptor-negative tumors (P less than 0.05). Epidermal growth factor receptor was expressed in 22 (43%) of the tumors analyzed and found to a greater degree in estrogen-receptor-negative and high-grade tumors (P less than 0.025). A significant correlation between neu and EGF-R expression was also noted. Tumors expressing membranous staining of neu had a greater than 70% chance of expressing EGF-R (P less than 0.01). Expression of TGF alpha was found in 68% of tumors and TGF alpha was detected in grade 1 and 2 tumor to a greater degree than EGF-R. The authors conclude that assaying tumors for these antigens may give additional phenotypic characteristics that can give further insight into the biology of breast cancer.

Adult↗
PubMed1990

Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990.

The effect of a synthetic analogue of CCK (Thr4,Nle7CCK-9) on growth of SW-1990 human pancreatic cancer was examined in two experimental models. Nude mice bearing SW-1990 pancreatic cancer xenografts were injected with CCK (5, 15, or 25 micrograms/kg) or vehicle twice daily for 20 days. Animals were then sacrificed and tumor volume, weight, protein, and deoxyribonucleic acid (DNA) content were evaluated. SW-1990 cells were grown in vitro and the effects of CCK, secretin, vasoactive intestinal peptide (VIP), and proglumide (a CCK-receptor antagonist) on cell number and DNA synthesis were determined. The highest dose of CCK, 25 micrograms/kg, significantly increased tumor weight, protein content, and DNA content (P less than 0.005). In vitro, CCK caused significant increases in cell counts of up to 47% at six days and 66% at 12 days compared to control. Graded concentrations of CCK had a biphasic effect on DNA synthesis with significant increases of up to 65% (P less than 0.005). CCK-induced cell proliferation was inhibited by proglumide. Secretin slightly increased cancer cell growth, although not as potently as CCK, VIP or secretin in combination with CCK did not show potentiation. These results indicate that growth of some human pancreatic cancers may be influenced by gastrointestinal peptides, of which CCK is the most potent.

Adenocarcinoma↗
PubMed1990

Effects of a high-fat diet and L364,718 on growth of human pancreas cancer.

The effects of a high-fat diet and the CCK-receptor antagonist, L364,718, were examined on growth of human pancreas cell line SW-1990 xenografted to nude mice. Sixty animals were fed either low-fat (4.3%) or high-fat (20.25%) diet. Fifteen mice in each diet group were treated with L364,718 (2 mg/kg) subcutaneously twice daily for 23 days. On day 24 the animals were sacrificed. Tumor and animal pancreases were dissected and evaluated for weight, protein, and DNA content. When comparing within each diet group, L364,718 significantly decreased tumor volume, weight, protein, and DNA content compared to untreated mice (P less than 0.005). Tumor volume and protein content were significantly larger in untreated animals on the high-fat diet (P less than 0.05) compared to the low-fat diet. Mouse pancreatic weight, protein, and DNA content per kilogram of animal weight were all significantly lower (P less than 0.005) in mice on the low-fat diet treated with L364,718. Pancreatic DNA content was also decreased in both groups of animals on the high-fat diet compared to untreated mice on the low-fat diet. These findings suggest that diets high in unsaturated fat promote the growth of human pancreatic cancer. Since both tumor and pancreas growth are inhibited by the specific CCK-antagonist, L364,718, it is possible that endogenous CCK promotes the growth.

Animals↗
PubMed1990

Neuroblastoma and parental occupation.

A matched case-control study of neuroblastoma investigated parental occupational risk factors. Cases diagnosed in 1970-1979 were identified through tumor registries in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone exchange. Parents of 104 matched pairs were interviewed by telephone. In contrast to results of a previous study, no significant associations were noted for paternal employment in a job cluster of occupations in electricity, electronics, insulation, utility, and printing; in jobs with electromagnetic field exposure; or in jobs as workers in electronics. Six cases and one control, however, had a father or mother who worked in electrical or electronic products assembly.

Case-Control Studies↗
PubMed1990

The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone.

In a prospective randomized trial designed to study the effectiveness of adjuvant chemotherapy following standard surgical treatment and radiation therapy, 233 eligible patients with medulloblastoma were treated by members of the Children's Cancer Study Group and the Radiation Therapy Oncology Group. Eligible patients were randomly assigned to receive radiation therapy with or without adjuvant chemotherapy consisting of 1-(2-chloroethyl)-3-cyclohexyl-nitrosourea (CCNU), vincristine, and prednisone. The estimated 5-year event-free survival probability was 59% for patients treated with radiation therapy and chemotherapy and 50% for patients treated with radiation therapy alone, a difference which is not statistically significant. The 5-year survival probability was 65% for both groups. Although the treatment difference was not statistically significant when all patients were combined, in the small number of patients with more extensive tumors, event-free survival was better in the group receiving chemotherapy (48% vs. 0%, p = 0.006). In these latter patients the survival time is also significantly prolonged. Extent of disease (as measured by the M staging criteria described by Chang) and age at diagnosis were significantly associated with outcome; advanced disease and young age had a worse prognosis. The extent of tumor resection was not an independent prognostic factor. It is concluded that chemotherapy does not benefit patients with low-stage medulloblastoma, but may benefit those with more advanced stages of disease.

Adolescent↗
PubMed1989

Parental occupation and Wilms' tumor: results of a case-control study.

Parental occupational exposures for Wilms' tumor were investigated in a pair-matched case-control study. The timing of the exposures in relation to the child's conception and birth was studied, as were the two forms of Wilms' tumor: genetic (prezygotic origin) and nongenetic (postzygotic origin). Cases who were under 15 yr of age at diagnosis during 1970 to 1983 were identified through the registries of three main hospitals treating childhood cancer in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among blacks, results are reported only for the 88 white matched pairs whose parents participated in telephone interviews. Children whose fathers held jobs in a job cluster that consisted mostly of machinists and welders were at significantly increased risk. The increase was highest for preconception exposure (odds ratio = 5.3, P = 0.006). The effect of preconception exposure was higher for the 26 genetic cases than for the 42 nongenetic cases. The other 20 cases were excluded from the subgroup analyses for various reasons. Further analyses did not elucidate an exposure common to machinists and welders that might explain the findings.

Adult↗
PubMed1989

Surgical quality control in head and neck cancer. Study 73-03 of the Radiation Therapy Oncology Group.

The measurement of quality of medical care has always been a topic of concern to physicians and other health care professionals. During an age of increasing competitiveness in the health care environment, the ability to assess accurately the quality of the care delivered has become increasingly important. The head and neck surgeons within the Radiation Therapy Oncology Group have examined this problem and have developed an evaluation tool that was then applied retrospectively in an attempt to evaluate the quality of surgery performed in a randomized study. The analysis of the results suggested that the retrospective approach to surgical quality control is fraught with hazards and is unlikely to fulfill the goals set for it.

Clinical Trials as Topic↗
PubMed1989

Patient age as a factor in radiotherapy. Data from the patterns of care study.

We studied the effect of patient age on treatment decisions related to radiation therapy using data obtained through the Patterns of Care Study. Definitive treatment given for breast cancer (191 patients) and palliative therapy given for a variety of symptoms (784 patients) were investigated using data collected from 49 facilities selected on a random basis to reflect fairly the national practice of radiotherapy. Elderly (aged 70 or older) patients accounted for 28.6% of the palliatively treated patients and 19.5% of the definitively treated breast patients. No correlation was found between patient age and the dose or number of days used in palliative therapy. Older patients were more likely to have the "boost" dose of radiation to the tumor bed delivered through external rather than implant techniques. While statistically significant, this difference is not felt to be clinically important. We conclude that once a patient is selected for a course of radiation therapy, age per se, is not a basis for prejudicial treatment.

Adult↗
PubMed1989

Synthesis of a gene encoding parathyroid hormone-like protein-(1-141): purification and biological characterization of the expressed protein.

PTH-like proteins (PTHLP), which are associated with humoral hypercalcemia of malignancy, have recently been purified. Isolation of their corresponding cDNAs has revealed that they are derived from a single gene. In this report a synthetic gene encoding PTHLP-(1-141), a 141-amino acid protein corresponding to the most abundant PTHLP cDNA detected in human tumors, was expressed in bacteria and purified to homogeneity. Recombinant (r) PTHLP-(1-141) migrates with an aberrantly high mol wt on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, presumably as a result of its unusually basic pI. rPTHLP-(1-141), like PTH, induced hypercalcemia in rats, caused release of 45Ca from fetal rat bones, and stimulated the synthesis of cAMP by rat osteosarcoma cells and canine renal membrane preparations. A comparison of the abilities of rPTHLP-(1-141) and bovine PTH-(1-34) to stimulate cAMP synthesis indicated rPTHLP-(1-141) to be 5-fold more potent in the osteosarcoma assay, while nearly 30-fold less active in the renal membrane adenylate cyclase assay. Although 100-fold less potent than bovine PTH-(1-34) in promoting bone resorption, rPTHLP-(1-141) was a potent calcemic factor in vivo, inducing a rise in serum calcium from 10.4 to 14.5 mg/dl when infused into rats at 1.3 micrograms/h. These results support previous assumptions that PTHLP is the humoral factor responsible for humoral hypercalcemia of malignancy. In addition, they suggest substantial differences between PTHLP and PTH in the regulation of calcium homeostasis.

Animals↗
PubMed1988

Practice patterns of palliative care for the United States 1984-1985.

This study reports the national averages for patterns of palliative radiation therapy observed in the United States for patients treated in 1984-1985 and compares those patterns to the pertinent literature. The data were collected in 1984-1985 by the Patterns of Care Study Survey of Palliative Care conducted in 49 institutions selected to provide valid national averages for the practice patterns reported. Data were collected from 784 patient records selected from five "strata" of practice. Demographic data and process data were tabulated and national averages were calculated from the data. Four metastatic sites were selected, weight bearing bones (401), non-weight bearing bones (102), brain metastasis (224), and lung-mediastinum (57). The median patient age was 63 years, equally divided by sex. In 52% of patients this was the first metastasis. Common Karnofsky performance scores ranged from 40 to 80%. Lung, breast, and prostate were the most common primaries. Two-thirds of the patients were treated by linear accelerators, one-third by cobalt. The median number of fractions was 10, median dose 3000 cGy, median fraction size 300 cGy, and median treatment duration 15 days. The goal of treatment was relief of pain (98%) and return of function (30%) for weight bearing bones, for brain metastasis it was preservation of function (68%), pain relief (33%), and relief of compression (25%). All sites showed TDF values that ranged from 33-85, and a TDF of approximately 65 was most common for weight bearing bones and brain metastasis with no consistent pattern of TDF selection for the other sites. Compliance by strata of practice with work-up criteria was excellent with isolated poor compliance seen in several strata.

Age Factors↗
PubMed1987

Purification of bovine protoporphyrinogen oxidase: immunological cross-reactivity and structural relationship to ferrochelatase.

Protoporphyrinogen oxidase, the penultimate enzyme in the haem biosynthetic pathway has been purified to apparent homogeneity from bovine liver mitochondria, by a published method (Dailey, H.A. and Fleming, J.E., (1983)), with an additional ion-exchange chromatography step, using a Mono Q column on an FPLC-system. This gave a product with a 68% yield and 870-fold purification. Protoporphyrinogen oxidase (EC 1.3.3.4) has an apparent Mr of 57,000 and the Km for protoporphyrinogen IX was 16.6 microM. Activity of the isolated enzyme was increased by 66% in the presence of oleic acid, and evidence was obtained for a FAD prosthetic group. Ferrochelatase (EC 4.99.1.1) was purified and antibodies were raised in rabbits against ferrochelatase and protoporphyrinogen oxidase, respectively. Anti-protoporphyrinogen oxidase IgG showed marked cross-reactivity with ferrochelatase and anti-ferrochelatase IgG cross-reacted with protoporphyrinogen oxidase. In addition, radiolabelled peptides of both enzymes, generated by chymotrypsin, demonstrated common peptides when analysed by two-dimensional chromatography.

Animals↗
PubMed1987

Antisecretory activity of misoprostol, its racemates, stereoisomers and metabolites in isolated parietal cells.

Inhibition of histamine-stimulated acid secretion by misoprostol was compared to its racemates, stereoisomers and metabolites in isolated canine parietal cell preparations. The concentration of misoprostol required to inhibit 50% of maximal histamine-stimulated acid secretion (IC50) was 3.8 +/- 0.3 nM. One racemate of misoprostol was at least 1000 times more potent than the other. Of the four misoprostol stereoisomers, the 11R, 16S isomer exhibited the most potent activity against histamine with an IC50 value of 1.4 +/- 0.1 nM. The acid metabolite of misoprostol was equally potent as misoprostol. In contrast to the acid metabolite, the beta-oxidation metabolites of misoprostol lacked significant activity at 1 microM. The results indicate that: 1) the acid metabolite of misoprostol may play a significant role in the antisecretory activity of misoprostol, and 2) the high degree of stereo-specificity associated with the antisecretory effects indicates that the activity of misoprostol may be receptor mediated.

Alprostadil↗
PubMed1979

Long term follow-up of combination chemotherapy-radiotherapy of stage III Hodgkin's disease: a Cancer and Acute Leukemia Group B study.

The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy-radiotherapy on Stage III Hodgkin's disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow-up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease-free survival in patients receiving radiation +/- chemotherapy is 23% (19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty-one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determined for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.

Adult↗