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

The growth curve of monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, is represented by an everbending curve on a semilogarithmic plot; however, the curve can be fitted by a straight line on a linear-linear plot. This unusual growth pattern suggests that, instead of a fixed proportion of the population, a fixed number of ARH-77 cells divide per unit time. The following are cell cycle transit time parameters calculated from percent labeled mitosis experiments: TG1, 10.0 +/- 3.5 hours; Ts, 14.3 +/- 2.3 hours; TG2, 4.3 hours; TM, 1.4 +/- 1.3 hours; and Tc, 30.0 +/- 6.1 hours. For cells exposed continuously to 3H-thymidine the values are: growth fraction, 67%; TG1, 6.5 hours; Ts, 13.0 hours; and TG2 + M, 3.0 hours. The average doubling time is 4.6 days (range, 3.8-4.7 days); after about 10 to 15 days in culture, the growth rate of freshly passaged cells declines markedly, as reflected by a growth curve with a much shallower slope. The changes are accompanied by a marked decline in the labeling index from 41.3% (range, 28.9%-53.7%) during the first 3 days of culture to less than 5% measured on day 21. Flow cytometry for DNA content-dependent cell cycle compartment distribution demonstrates an obvious decline in the proportion of S-phase cells and a marked accumulation of G2 phase cells as the cultures age. When the supernatant medium of ARH-77 cells grown for 10 days is replaced by fresh medium, a new burst of vigorous cellular growth is observed with a curve slope similar to that observed during the first 5 days of culture. If the 10-day-old supernatant medium is used to set up cultures with freshly harvested ARH-77 cells, their growth curve resembles that of 10-day-old cultures. However, this supernatant medium induces no decrease in the growth rate of other human tumor cells, suggesting that inhibition of cellular growth does not result from exhaustion of nutrients, but that ARH-77 cells produce a molecular mediator that specifically inhibits the growth of these cells. ARH-77 cells could be synchronized with a single treatment of 3 or 5 mM thymidine; (dThd) and cloning efficiency was 2% to 4% in a double-layer soft agar assay. Treatment for 1 hour with increasing concentrations of melphalan produced a threshold exponential survival curve (Dq = 0.45 microgram/ml and D0 = 0.35 microgram/ml, 1 hour).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:ARH-77, an established human IgG-producing myeloma cell line. II. Growth kinetics, clonogenic capacity, chalone production, xenogeneic transplantations, and response to melphalan. 623 73

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.21 +/- 0.11 ng/ml to a maximum of 0.42 +/- 0.20 ng/ml on day 4 after tumor transplantation, 1 day before serum Ca increased. The serum CT levels declined again the following day (day 5). In thyroidectomized, parathyroid autotransplated rats with HWCS 256, serum Ca increased 1 day earlier than in intact rats. Substitution of CT by exogenous CT injections delayed the hypercalcemia for one day. Ca loading was followed by a decreased serum CT level (delta CT); the CT content of the thyroid fell from 9.4 +/- 1.1 ng/mg wet wt to 1.0 +/- 0.3 ng/mg wet wt. While hypercalcemia was present. Also chronic intraperitoneal Ca administration induced a decrease in the CT response to a Ca load (delta CT) and a decrease in thyroid CT content from 9.32 +/- 0.58 ng/mg wet wt to 3.84 +/- 0.33 ng/mg wet wt. These changes were no longer present 4 days after stopping Ca administration. In chronic hypercalcemia induced by 1,25(OH)2D3 administration, basal serum CT levels did not vary significantly, whereas serum Ca increased to 11.8 +/- 0.46 mg/dl on day 4. CT after an acute Ca load was diminished, as was CT content of the thyroid during 1,25(OH)2D3 administration. These changes were reversible after stopping 1,25(OH)2D3 administration. During chronic hypercalcemia a reversible exhaustion of CT content of the thyroid and a diminished CT response to acute Ca stimulation was observed, while basal serum CT levels remained unchanged.
 ...
PMID:Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia. 654 97

In contrast to young mice, old mice fail to reject a transplanted challenge of the highly immunogenic, ultraviolet light-induced tumor 1591-RE. Old mice also fail to mount a cytolytic tumor-specific immune response in vivo, and spleen cells of old mice are defective in their ability to generate tumor-specific T cells in vitro. In the present study we report the results of cell culture mixing experiments that show that this deficiency is due to a decreased responsiveness of the Lyt-2+ tumor-specific cytolytic T cell precursors of the old animals. We also demonstrate with limiting dilution analysis that the defective responsiveness is not due to a clonal exhaustion of the precursors. In fact, the responsiveness could be restored in vitro by culturing the spleen cells of old animals at high density or by the addition of excess Lyt-1-/Lyt-2-/2000-rad-resistant spleen cells from young or old mice. Our results suggest that the rescue of tumor immunity in old individuals may be possible, perhaps by educating effector cells in vitro for adoptive immunotherapy.
 ...
PMID:Rescue of the tumor-specific immune response of aged mice in vitro. 660 95

Cancer may affect hemopoiesis by altering the proliferative status of hemopoietic progenitor cells. In Lewis lung carcinoma (LLC), the proliferative rate of the granulocyte-macrophage colony-forming unit (culture) (GM-CFUc) was studied using in vivo hydroxyurea techniques. The disposal of mature elements to the periphery was also monitored during tumor growth. Neutrophilia, anemia, and splenic hypertrophy developed during the course of the disease. By Day 6 post-tumor implant, myeloid hyperplasia of the marrow was evident, but the content of GM-CFUc in LLC mice was similar to that of control. However, by Day 11, the marrow of LLC mice displayed an increased concentration of GM-CFUc, which tripled by Day 19. There was an increased percentage of proliferating GM-CFUc in LLC mice by Day 6 which was highest by Day 11 and thereafter declined. The level of colony-stimulating activity was higher in the serum of tumor bearers than in that of controls. The early increase in proliferative rate of these early hemopoietic precursors can account for the later accumulation of GM-CFUc and myeloid elements in the marrow. Increased cycling of hemopoietic stem cells raises questions concerning the potential for early exhaustion of hemopoietic progenitor cells in these animals.
 ...
PMID:High proliferation of granulocyte-macrophage progenitors in tumor-bearing mice. 688 22

Seventy malignant lymphomas of the gastro-intestinal tract (GIT) (54 lymphosarcomas, 16 lymphogranulomatoses) were studied. GIT lymphosarcomas and lymphogranulomatosis are characterized by the similarity of histogenesis, morphogenesis, and forms of progression. The lymphoid apparatus of GIT is the source of tumor growth, the tumor develops multicentrically and not simultaneously, the progression occurs as autochthonous growth, metastasizing. Isolated GIT lymphomas have a potential trend for generalization. In lymphosarcomas, the predominant histological types are prolymphocytic and lymphoblastic, in lymphogranulomatosis--mixed-cell and lymphocyte exhaustion. Differential diagnosis must distinguish between malignant lymphoma and pseudolymphoma, different variants of lymphomas and low-differentiated carcinoma, which requires examination of the operation material, knowledge of the typical cytological and histological features of lymphoma variants, and the use of the required complex of histological and histochemical methods.
 ...
PMID:[Malignant lymphomas of the gastrointestinal tract (problems of histogenesis, morphogenesis and histological diagnosis)]. 712 27

The localization of proteasome epitopes in the lung cancer cell lines NCI-H82, derived from a small cell lung cancer, and MR65, derived from a squamous cell lung carcinoma, was studied in relation to cell growth conditions. For this purpose the proteasome monoclonal antibodies MCP34 and MCP20 were applied to the cells growing under different nutritional conditions, resulting in different proliferative states. Using indirect immunofluorescence microscopy with brief fixation in methanol (5 sec, -20 degrees C) followed by three dips in acetone (5 sec at room temperature), it became obvious that the intracellular detectability of the proteasomes changes depending on the nutritional and proliferative status of the tumor cells. Two types of experiments were carried out: (1) cells were grown for two days at different cell densities, with an excess of culture medium, and (2) cells were seeded in a low cell density and monitored for 6 days without change of medium. In cells grown at low density, the proteasomes can be detected mainly in the nuclei, while the nucleoli are almost devoid of staining, and the cytoplasm is only slightly stained. In cells grown at high density, the staining pattern changes with a much less pronounced nuclear staining than in the cells at low density, while the cytoplasm remains slightly stained. In the nutrient depletion experiment similar changes were seen. In cells growing under favorable conditions (1 or 2 days in fresh medium) proteasomes are detected mainly in the nuclei, whereas when the medium becomes depleted of nutrients (4 or 5-day-old medium) the staining pattern changes to one with a much less pronounced nuclear staining. However, in immunofluorescence studies on cells grown under similar conditions but fixed in ethanol (-20 degrees C) for 15 min, the changes in proteasome localization pattern were not detected during medium depletion. Using this fixation protocol the proteasomes are detected mainly in the nuclei at all stages of the medium exhaustion experiment. These apparently contrasting results suggest that upon nutrient depletion the proteasome epitopes become less accessible to the antibodies used. Apparently, the epitopes can regain accessibility if an extended ethanol fixation is used. This hypothesis was confirmed by flow cytometry and immunoblotting experiments. In flow cytometry of ethanol-fixed cells the fluorescence intensity of only a minor part of the cell population decreases to some extent with medium depletion, but in the majority of the cells fluorescence remains at its initial level. The immunoblotting experiments show no quantitative changes in proteasome content of the tumor cells at the different growth conditions.
 ...
PMID:Changes in immunocytochemical detectability of proteasome epitopes depending on cell growth and fixation conditions of lung cancer cell lines. 753 47

This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18-35 m/min, 2-4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).
 ...
PMID:Exercise increases inflammatory macrophage antitumor cytotoxicity. 822 94

The alcoholic liver cirrhosis usually causes overall immunological changes which might be attributed to either the hepatic disease itself, to ethanol action and/or to malnourishment of the patient. These immune abnormalities comprise both cellular and humoral immunity, consisting of increased immunoglobulin levels, depressed late-skin response to antigens, lowered proliferative response of lymphocytes to mitogens, lower plasma levels of complement proteins (C3 and C4) and by either lower (IL2 and gamma IF) or increased (IL1, TNF, IL6 and IL8) cytokine levels. Parallel to the systemic immune suppression found in most patients, there is also a concomitant local, genetically based, immune stimulation at the liver level which leads to hepatic self-aggression. The systemic immune-suppression could be responsible for periodical infections or neoplasia found in these patients. The possible factors for the immune exhaustion are: a) lower hepatic clearance of toxins and/or bacteria; b) lower hepatic synthesis of complement components; c) cytokines (IL2 and gamma IF) deficiencies, and d) deficiencies of nutrients related to the antioxidant and/or immune defense mechanisms. The immune stimulation of the liver self aggression is characterized by the preferential migration of cytotoxic T cell and neutrophils to the liver, following stimulatory factors such as Mallory bodies, acetaldehyde and/or antibodies. Moreover, the local increase of cytokines (IL1, TNF, IL6 and IL8) levels would be liable for the local phagocyte chemotaxy (IL8) or part of liver injury (TNF) eased by the lower antioxidant defense of the cirrhotic liver.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Immunologic changes in alcoholic liver cirrhosis]. 854 Aug 5

Antiestrogens, particularly tamoxifen, are effective in the treatment of pre- and postmenopausal women suffering from all stages of breast cancer. Unfortunately, many patients become resistant to tamoxifen during therapy, which allows the tumor to progress. Thus, a preclinical recognition of tumor progression, i.e. by monitoring serum hormone levels, could be worthwhile. The serum levels of dehydroepiandrosterone sulfate and estradiol of postmenopausal women with advanced breast cancer treated by the new antiestrogen droloxifene were therefore checked. However, only non-significant changes in the hormone levels during droloxifene therapy were observed, and no relation was found between hormone levels and the course of the disease, success or exhaustion of droloxifene application, or development of tumor progression. Our data do not confirm earlier findings reported in the literature that measurement of hormones seems to be suitable for an early indication of tumor progression during an antiestrogen therapy before its clinical manifestation.
 ...
PMID:Steroid hormone levels in patients with advanced breast cancer during therapy with droloxifene: a pilot study. 862 3

Partial regression in cutaneous malignant melanoma has been reported by a number of observers, albeit not all, to be associated with a relatively poor prognosis; in contrast, a keratoacanthoma, which eventually regresses, does not metastasize. The Hammond effect could explain the possibly poor prognosis of the thin regressing melanoma. Hammond(W.G. Hammond et al., Cancer J., 8: 130-138, 1995) showed that the speed of biological progression to less differentiated phenotypes is directly related to the immunocompetences of the tumor hosts. If partial regression is a sign of an unusually strong immune reaction, then the melanoma that partially regresses might have a relatively poor prognosis because of the greater risk of biological progression among the surviving tumor clones. A Hammond effect is not associated with regression of a keratoacanthoma. I postulate that the growth of this tumor is accelerated, rather than restrained, by the immune reaction and that the ultimate regression of the tumor is the result, not of immune cytotoxicity, but of a rapid terminal differentiation (a reverse Hammond effect); alternatively, very rapid growth might lead to an exhaustion of growth potential before progression to clonal immortality could occur.
 ...
PMID:The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. 864 Jul 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>