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K Seibert

Publications and source records attributed to K Seibert.

90 records · Page 5Linked to original sources
PubMed1983

Cytogenetic studies of human breast cancer lines: MCF-7 and derived variant sublines.

Cytogenetic studies of the human breast cancer cell line MCF-7 and the sublines derived from it demonstrated extensive aneuploidy with both numerical and structural abnormalities and a wide range of heteroploidy. Detailed G-banding analyses showed that loss of marker chromosomes was a rare event, while formation of additional structural abnormalities was very common in these long-term cultures. All chromosomes were involved in these abnormalities. Loss of a morphologically normal X-chromosome may be related to the loss of estrogen receptors in these cell lines. With the exception of one subline, all cell lines had a short homogeneously staining region (HSR) on chromosome 7. Although the parent MCF-7 line had tetrahydrofolate dehydrogenase levels within the normal range, a lengthened HSR has been found in MCF-7 lines that are resistant to methotrexate. This observation strongly favors the association of an increased level of tetrahydrofolate dehydrogenase with HSR. In conclusion, the inherent genetic instability in this group of related cell lines may explain the heterogeneity found in this tumor. Continuous chromosomal rearrangements and numerical changes may reflect an ongoing process of selection and adaptation in these cell lines established from a breast carcinoma and may be characteristic of the aggressiveness of this neoplasm.

Aneuploidy↗
PubMed1981

Cardiac metastasis from osteosarcoma.

A case of osteosarcoma metastatic to the heart demonstrated by computed tomography (CT) is reported. Although the prognosis is poor, successful excision of such a metastasis has been reported previously. It is pertinent to examine the heart for metastases by CT, since these patients may be followed by this modality for the development of pulmonary metastases.

Adult↗
PubMed1980

Prognostic significance of serum lactate dehydrogenase in malignant lymphoma.

The pretreatment serum lactate dehydrogenase level (LDH) was the single most important prognostic variable in 30 patients with diffuse histiocytic lymphoma treated between January 1973 and January 1977 with a poly-drug chemotherapy program called the cyclophosphamide L2 protocol at the Memorial Sloan-Kettering Cancer Center. A highly significant difference was found between the survival patterns of patients with LDH levels of 500 U or less and those with LDH levels greater than 500 U. (Two-year survival rates were 67% and 13%, respectively.) A similar trend was observed for 25 patients with diffuse, poorly differentiated lymphocytic lymphoma treated with the same protocol, although this difference was not statistically significant. (Corresponding two-year survival rates were 74% and 33%, respectively.) The association of LDH level with survival was evident even after adjustment for other factors of potential prognostic significance. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced stage non-Hodgkin's lymphoma.

Antineoplastic Agents↗
PubMed1977

[Emergency treatment of haemophilia A with factor VIII inhibitors using activated prothrombin complex concentrates (author's transl)].

Severe rectal bleeding in a 6-year-old boy with haemophilia A and factor VIII inhibitors could not be stopped with factor VIII concentrates. But a good effect was achieved with activated prothrombin complex concentrates (fraction FEIBA), given over eight days. Amaurosis occurred as a complication after injection of the first dose, but disappeared completely within several minutes. Tests revealed accelerated intravascular coagulation with increased fibrin monomers and fibrin/fibrinogen degradation products.

Blindness↗
PubMed1976

The lysosomal enzymes of lymphocytes in the premature and the term infant.

Activity of acid phosphatase, beta-glucuronidase, and beta-glucosaminidase was determined in peripheral blood lymphocytes of 29 premature and 20 term infants with the use of cytochemical methods. The results were expressed semiquantitatively and included the total count of enzyme-positive and the enzyme-negative lymphocytes as well as the intracellular content of enzyme-positive and enzyme-negative lysosomal granules. The premature infant exhibited significantly lower activity of all the studied enzymes than the term infants. It thus argues in favour of the opinion that the lysosomal apparatus in lymphocytes undergoes development in the course of fetal maturation of the immune system. Evaluation of the activity of lysosomal enzymes in lymphocytes can serve as an indicator of fetal maturity and immunological status.

Acid Phosphatase↗
PubMed1975

Enzymatic equipment of lymphocyte lysosomes in the premature or term infants and in the adults.

The activity of some lymphocyte lysosomal enzymes such as: acid phosphatase, beta-glucuronidase and beta-glucosaminidase was studied comparatively in 29 prematures, 20 term infants and 20 adults. The activity of lysosomal enzymes was found to increase gradually in the course of fetal maturation and later on after birth. The percentage of lymphocytes exhibiting strong intracellular acid phosphatase and beta-glucuronidase activity was highest in adults. Differences between lymphocyte beta-glucuronidase activity in the term infants and that in adults were less evident. The results of the study seem to confirm the previous assumption of certain authors that B lymphocytes, generally characterized by a low activity of lysosomal enzymes, are more numerous in the premature and term infants than in the adults.

Acid Phosphatase↗
PubMedDate not supplied

Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.

Prostaglandins and glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism. Two isoforms of the membrane protein COX are known: COX-1, which is constitutively expressed in most tissues, is responsible for the physiological production of prostaglandins; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is responsible for the elevated production of prostaglandins during inflammation. The structure of ovine COX-1 complexed with several NSAIDs has been determined. Here we report the structures of unliganded murine COX-2 and complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, determined at 3.0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition.

Animals↗
PubMedDate not supplied

Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model.

Epidemiological and experimental studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk of human cancer, including breast cancer. Recently, research studies in our laboratories have shown that the selective cyclooxygenase-2 (COX-2) blocker, Celecoxib, given daily in the diet, significantly inhibited the induction of rat mammary tumors by 7, 12-dimethylbenz(a)anthracene (DMBA). These studies were extended to evaluate Celecoxib for its effectiveness as an antineoplastic agent in this rat mammary tumor model. We examined the growth inhibitory effects of Celecoxib, given daily in the diet, on the volume and the number of established mammary tumors, vis-a-vis the cancer load (CL). Tumors continued to grow actively in control rats fed chow diet only. In contrast, the Celecoxib-supplemented diet (1500 mg/kg diet) significantly decreased the size of the mammary tumors in rats over the 6 week treatment period, resulting in an average reduction in tumor volume of approximately 32%, relative to the baseline volume (p<0.04). At the end of the 6 week treatment period, average tumor volume was 1.45 cm3 and 0.13 cm3 in the control and Celecoxib treated rats respectively. Tumor regression occurred in 90% of the rats. In addition, new tumors continued to emerge in the control group, in contrast to their significantly decreasing numbers in the Celecoxib treated group over the same time period (p<0.05). These results indicate that Celecoxib has significant antineoplastic activity, in addition to its anticarcinogenic effects.

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

Dose-response effects of the COX-2 inhibitor, celecoxib, on the chemoprevention of mammary carcinogenesis.

Recent chemopreventive studies in our laboratories showed that the COX-2 inhibitor, celecoxib, inhibited the induction of mammary cancer by 7,12-dimethylbenz(a)anthracene (DMBA). In this study, we examined the relative chemopreventive effect of varying doses of celecoxib on the development and growth of DMBA-induced rat mammary tumors. At 10 days prior to receiving a single intragastric dose of 15 mg DMBA/rat, female Sprague-Dawley rats were fed a control chow diet or diets containing 250, 500, 1000 or 1500 ppm celecoxib until termination of the experiment. Administration of increasing doses of celecoxib inhibited mammary tumor incidence and multiplicity as well as tumor volume in a dose-dependent manner. At 122 days post DMBA-intubation, mammary tumor incidence was 100% in the control rats compared to 80%, 50%, 45% and 25% in rats receiving 250, 500, 1000 or 1500 ppm celecoxib, respectively (p<0.001). Similarly, tumor multiplicity and tumor volume were significantly reduced by increasing the dose of celecoxib from 250 to 1500 ppm in the diet. The control rats had an average of 3.46 tumors/rat compared to 1.80, 1.00, 0.75 and 0.50 tumors/rat in animals receiving 250, 500, 1000 or 1500 ppm celecoxib, respectively (p<0.001). Average tumor volumes in rats fed 250, 500, 1000 or 1500 ppm celecoxib were 0.42, 0.34, 0.31 and 0.16 cm3 compared to 1.29 cm3 in the control rats (p<0.001). There was a concomitant increase in the steady-state serum concentration of celecoxib with the dose. These results indicate that, in this rat model, the chemopreventive effect of celecoxib against breast cancer is dose-dependent and that celecoxib is effective even at lower dose levels.

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

Continuous streptozotocin infusion: a phase I study.

Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise.

Bone Marrow↗