Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effect of liposome size on liposome circulation time in the blood. Liposomes composed of phosphatidylcholine, cholesterol and ganglioside GM1 were prepared in the various size range. Optimal circulation activity (55% injected dose at 4 h post injection) of GM1-containing liposomes, which correlated with a relatively high uptake of liposomes by EMT6 tumor in mouse, was obtained with a size range of 70 to 200 nm in diameter. Increasing the diameter of liposome to greater than 200 nm resulted in an enhancement of the spleen uptake and decrease of the blood level. For liposomes with a diameter of less than 70 nm, 70% of the injected dose were taken up by the liver, presumably by the parenchymal cells. In contrast, the biodistribution of phosphatidylserine-containing liposomes was relatively insensitive to changes in liposome size; most of the injected dose was found in the liver. The effect of RES blockade on the circulation time of large (d greater than 300 nm), GM1-containing liposomes was also studied. Dextran sulfate 500, a commonly used blockade reagent for Kupffer cells, had no effect. On the other hand, preinjection of a large dose of liposomes with a diameter greater than 500 nm showed variable results depending on the lipid composition of the blocking liposomes. Preinjection of liposomes containing GM1, phosphatidylinositol or (N-polyethyleneglycol) phosphatidylethanolamine effectively reduced the spleen uptake of the large GM1-containing liposomes, whereas liposomes containing phosphatidic acid showed no effect. These results indicate that only spleen homing liposomes can be used as a blocking reagent to prolong the circulation time of the large GM1-containing liposomes.
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PMID:Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes. 155 Aug 58

Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.
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PMID:Borderline epithelial ovarian tumors: a review of 81 cases with an assessment of the impact of treatment. 155 78

Optimal management of locally advanced breast cancer is controversial. Claims of superiority for neoadjuvant systemic therapy are based on comparisons with outdated historical control groups who received no chemotherapy. Between 1978 and 1987, 118 patients with locally advanced breast cancer underwent treatment and follow-up at the Medical College of Virginia. Median follow-up was 44 months (range 3-119 months). Actuarial 5-year survival for the entire group was 54%. This compares favorably with recent series using neoadjuvant chemotherapy in which 5-year survival rates of 40-65% have been reported. Primary tumor size larger than 9 cm, metastases to more than 50% of regional lymph nodes, and the presence of inflammatory disease were significant prognostic indicators. This series represents a contemporary control group of patients with locally advanced breast cancer in whom conventionally accepted guidelines for local and postoperative systemic adjuvant therapy were used. Until the optimal sequence of therapy is determined by prospective randomized trials, series such as this may serve as more appropriate controls to which the results of new therapies could be compared.
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PMID:Stage III breast cancer: is neoadjuvant chemotherapy always necessary? 155 65

The human prostate tumor cell line LNCaP contains an abnormal androgen receptor system with broad steroid binding specificity. Progestagens, estradiol and several antiandrogens compete with androgens for binding to the androgen receptor in the cells to a higher extent than in other androgen sensitive systems. Optimal growth of LNCaP cells is observed after addition of the synthetic androgen R1881 (0.1 nM). In addition, estrogens, progestagens and several antiandrogens do not inhibit androgen responsive growth, but have striking growth stimulatory effects and increase EGF receptor level and acid phosphatase secretion. We have found that the androgen receptor in the LNCaP cells contains a single point mutation changing the sense of codon 868 (Thr to Ala) in the ligand binding domain. Expression vectors containing the normal or mutated androgen receptor sequence were transfected into COS or HeLa cells. Androgens, progestagens, estrogens and several antiandrogens bind the mutated androgen receptor protein and activate the expression of an androgen-regulated reporter gene (GRE-tk-CAT), indicating that the mutation directly affects both binding specificity and the induction of gene expression. Interestingly, the antiandrogen casodex showed antiandrogenic properties in growth studies of LNCaP cells and did not induce reporter gene activity in Hela cells transfected with the mutant receptor. The mutated androgen receptor of LNCaP cells is therefore a useful tool in the elucidation of different levels of action of steroids and antisteroids.
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PMID:The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. 156 39

Adrenocortical carcinoma (ACC) in childhood is a rare tumor with high fatality rate. Available reports provide event free survival rates ranging between 10 to 50%. Optimal treatment has not yet been established; surgery plays a major role, and the value of adjuvant chemotherapy needs to be evaluated further, especially in children who develop recurrent disease and those with metastases at diagnosis. Optimal therapy of ACC has not been established. Surgery has been curative after complete tumor resection. Children with inoperable, recurrent and metastatic ACC have been treated with O,P'DDD, with response rates ranging from 10 to 60% in different series [7,11-20]. Radiotherapy [21] and other anti-cancer drugs have been used [4-22] but their efficacy has not been established. Combination chemotherapy containing oncovin, cisPlatinum, epipodophyllotoxin and cyclophosphamide (OPEC) produced regression of metastatic ACC in a 5-year-old male [23]. We report one girl with relapsed disseminated ACC who showed good, even if temporary, control of the disease, with disappearance of lung, liver and spleen metastases, and marked reduction of the adrenal mass, following combined chemotherapy according to the "eight-drugs-in-one-day" protocol.
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PMID:Partial response after intensive chemotherapy for adrenal cortical carcinoma in a child. 157 38

The interaction between sulfonylureas and membrane proteins from a hamster insulin-secreting tumor (HIT) cell line has been examined. Four HIT cell membrane proteins were covalently linked to an 125I-labeled glyburide analog by photolabeling. Three photolabeled polypeptides of M(r) 65,000, 55,000, and 30,000 were identified as low affinity "glyburide receptors." These proteins appear to be of similar abundance, when quantitated by photolabeling, with half-maximal displacements (Ki values) by glyburide, glipizide, and tolbutamide in the low micromolar range. The glyburide analog is more tightly bound to a M(r) 140,000 protein with dissociation constants, determined by filtration binding assays and by photolabeling, of 7 and 9.0 nM, respectively. The labeled analog was displaced from the M(r) 140,000 protein by glyburide, glipizide and tolbutamide with Ki values of 3.3 nM, 103 nM, and 25 microM, respectively, as estimated by photolabeling. Optimal conditions established for visualizing the M(r) 140,000 band on autoradiograms prepared after UV cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis include irradiating the radioligand-receptor complex at 1.5 J/cm2 at 312 nm, followed by heating samples in pH 9.0 sodium dodecyl sulfate-gel sample buffer. With receptor sites partially occupied (5 nM radioligand), approximately 0.75% of the protein is photocoupled to the radioligand and visualized by autoradiography. Our results confirm that the M(r) 140,000 polypeptide contains the beta-cell high affinity glyburide binding site and show that the second generation sulfonylurea antidiabetic drugs have a selective increase in affinity for this receptor.
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PMID:Specificity of photolabeling of beta-cell membrane proteins with an 125I-labeled glyburide analog. 163 33

Three cases of pleomorphic xanthoastrocytomas (P.X.A.), a low grade leptomeningeal glioma are reported. Prominent histological features used for diagnosis were a cellular pleomorphism of G.F.A.P. positive cells, with intracytoplasmic lipidic vacuols. A reticulinic network and mononuclear cells infiltrates have been observed. A weak mitotic activity and lack of necrosis and of endothelial cells proliferation were significant additional features necessary for diagnosis. Our cases were observed during the surgical management of young patients with resistant epilepsy. Neuroradiological examinations showed a tumor superficially located within the temporal or the parietal lobe. This tumor could be calcified and/or cystic. Operative aspects showed a firm and non-encapsulated leptomeningeal tumor with possible various colors. Our patients were seizures-free after surgery even during the follow-up. From the currently reported cases clinical follow-up ranging for 1.5 to 3 years is not sufficient to predict a favorable carcinologic prognosis. P.X.A. is an uncommon tumor and less than 50 cases are reported throughout the literature. This tumor affecting young subjects mainly during the second decade is revealed in the majority of cases (3/4) by epileptic seizures, less frequently by a deficit or by an intracranial hypertension. The great majority of clinical events are observed before 20 years. The functional prognosis is rather good after surgery with a disappearance of epileptic fits in about 50% of the cases. Throughout the literature the prognosis of this tumor seems to be comparable to low-grade astrocytomas. Optimal management of P.X.A. seems to be primary surgical resection with later surgery for residual or recurrent tumor. The role of radiotherapy in the management of P.X.A. is at this time uncertain.
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PMID:[Pleomorphic xanthoastrocytoma. Apropos of 3 new cases. Review of the literature]. 166 56

Optimal surgery for breast cancer demands effectiveness in local disease control, minimal physical and psychosocial morbidity, and efficient use of resources for assessment, diagnosis, treatment, and follow-up. These issues are addressed below with particular emphasis on the biologic relevance of tumor recurrence for planning local treatment, the management of subclinical radiographic abnormalities, the degree of importance of the timing of surgery in the menstrual cycle, and the value of axillary dissection.
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PMID:Surgery for early breast cancer. 166 28

The therapeutic efficacy of adoptive immunotherapy of cancer has been shown to positively correlate with the dose of tumor-immune T cells transferred. Therefore, the success of this therapy is critically dependent on the ability to procure large numbers of functionally active T cells. Previous studies in animal models have shown that the limited therapeutic efficacy of a small number of immune T cells can be greatly enhanced by expansion of T cells in vitro to greater numbers before transfer in vivo. Optimal regimens for T cell expansion in vitro have generally employed the use of intermittent stimulation of the TCR with specific Ag followed by exogenous IL-2. The use of IL-2 alone does not provide for requisite episodic up-regulation of IL-2R. Stimulation of the invariant CD3 portion of the TCR/CD3 complex with antibody to CD3 (anti-CD3) represents an alternative method of up-regulating IL-2R and has been used to nonspecifically induce the growth of Ag-specific T cell lines and clones long-term in vitro with maintenance of function and specificity. The current study examined whether resting T cell populations containing small numbers of memory tumor-specific T cells could be rendered more effective in tumor therapy by nonspecific expansion in vitro with anti-CD3 plus IL-2. Spleens from C57BL/6 mice previously immunized to FBL-3, a syngeneic virus-induced leukemia, were nonspecifically stimulated with anti-CD3 plus IL-2. The resultant T cells were expanded in number, were nonlytic to FBL-3 but retained the ability to become lytic upon specific stimulation by FBL-3, and were effective in specific tumor therapy. The Ag-specific anti-tumor immune function declined on a per cell basis after each cycle of anti-CD3-induced T cell expansion. However, the approach resulted in a substantial increase in total T cell number and an overall net increase in the function of the effector T cell population. Thus, stimulation of tumor-immune T cell populations with anti-CD3 plus IL-2 represents a nonspecific method for expanding the number of specific effector T cells for cancer therapy.
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PMID:T cells from tumor-immune mice nonspecifically expanded in vitro with anti-CD3 plus IL-2 retain specific function in vitro and can eradicate disseminated leukemia in vivo. 167 58

Four monoclonal antibodies reactive with the rod portion of human cytokeratin No. 8 were evaluated using experimental tumour radio-immunolocalization. Nude mice carrying human HeLa cell tumours were injected with 125I-labelled F(ab')2 fragments or intact IgG antibodies. Positive immunolocalization was observed with all the specific antibodies, the intact antibodies being superior to their analogous F(ab')2 fragments. High localization efficiency was observed despite the fact that the targets are intracellular filaments. The presence of necrotic areas in the tumours may favour the high uptake in the tumours. By computerized gamma-scintigraphic evaluation of the antibody distribution in the animals, several kinetic parameters of the antibody behaviour in vivo could be determined. The biological half-lives in the tumours were determined to be greater than 600 h for some of the antibodies compared to a half-life of 40-80 h in non-tumour tissues. Optimal imaging was obtained as late as 10-14 days after administration of the antibody. Up to 10% of the injected antibody could be identified in the tumours, indicating a potential value in radio-immunolocalization and radio-immunotherapy using anticytokeratin antibodies.
Tumour Biol 1990
PMID:Radio-immunolocalization in nude mice using anticytokeratin monoclonal antibodies. 169 11


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