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Biomedical subjects

G C Li

Publications and source records attributed to G C Li.

At least 91 records · Page 5Linked to original sources
PubMed1988

[Surgical treatment of breast cancer in elderly women--analysis of 244 patients].

From April 1964 to December 1981, 244 patients, women over 60 years old, with unilateral breast cancer were treated by surgery in our hospital. In this series, 15 patients (6.1%) had Stage I, 131 (53.6%) Stage II, 82 (33.6%) Stage III and 16 (6.6%) unstaged lesions. Of these patients, 3 were treated by extended radical mastectomy (ERM), 140 by standard radical mastectomy (SRM), 49 by modified radical mastectomy (MRM) and 52 by total mastectomy (TM). Except 52 cases by TM, axillary lymph node metastasis rate in 192 patients of this series was 49.3%. The 5- and 10-year survival rates were 33.3% in ERM group, 53.4% and 39.5% in SRM group, 70.8% and 48.5% in MRM group, and 73.4% and 55.3% in TM group, respectively. The overall 5-and 10-year survival rates were 62.1% and 45.6%. In Stage I, II patients, the 5-and 10-year survival rates of TM group were much higher than those of SRM and MRM groups (P less than 0.01), but in Stage III, the 5- and 10-year survival rates of MRM group were higher than those of other groups (P less than 0.05). Noticeably, the 5- and 10-year survival rates of SRM group in Stage I approximately III were not satisfactory. Our data show that the postoperative radiotherapy or chemotherapy was ineffective in elderly patients with breast cancer.

Aged↗
PubMed1988

Stable H2O2-resistant variants of Chinese hamster fibroblasts demonstrate increases in catalase activity.

Hydrogen peroxide (H2O2)-resistant variants of the Chinese hamster ovary HA-1 line have been derived by culturing cells in progressively higher concentrations of H2O2 (greater than 200 days, in 50-800 microM H2O2). The H2O2-resistant phenotype has been stable for over 60 passages (240 days) following removal from the H2O2 stress. The resistant cells demonstrate both increased capacity to deplete exogenously added H2O2 from the growth medium and increased catalase activity. H2O2 resistance correlates well with catalase activity. An increase in chromosome number occurred in the cells adapted to 200-800 microM H2O2, but increases in aneuploidy and tetraploidy were not necessary for resistance. These results suggest that adaptation to chronic oxidative stress mediated by H2O2 in mammalian cells is accompanied by a stable heritable change in expression of catalase activity.

Animals↗
PubMed1987

Influence of oxidative stress induced by cysteamine upon the induction and development of thermotolerance in Chinese hamster ovary cells.

Chinese hamster ovary cells exposed to the sulfhydryl compound cysteamine combined with heat treatment at 44 degrees C developed thermotolerance within 8 h. After initial treatment either with 15 min cysteamine (0.4 mM) at 37 degrees C immediately followed by 15 min heat at 44 degrees C or with 15 min cysteamine (0.4 mM) at 44 degrees C, the magnitude of thermotolerance developed was identical. The D0 of the subsequent 44 degrees C heat survival curves increased by factors of 8.9 and 7.9, respectively. The kinetics of thermotolerance induction and the time to reach the maximum of thermotolerance expression after combined cysteamine treatment at 44 degrees C for 15 min was found to be comparable to the effects of 44 degrees C treatment alone for 30 min. The synergistic effect of cysteamine with the conditioning heat treatment at 44 degrees C was blocked by catalase (50 micrograms/ml). Following initial treatment with cysteamine at 37 degrees C, cells became thermotolerant within 2 h. The D0 of the survival curves for 44 degrees C heat treatments increased with duration (t1 = min, 37 degrees C) of the cysteamine (0.4 mM) exposure; e.g., the D0 increased by factors of 1.5, 1.6, 2.2, and 2.6 for t1 = 30, 60, 90, and 120 min. The induction of thermotolerance by cysteamine at 37 degrees C was completely blocked by the addition of catalase (50 micrograms/ml), present during the initial period of drug treatment. Combined cysteamine and heat treatment at 44 degrees C, but also cysteamine exposure at 37 degrees C, enhanced synthesis of heat shock proteins. The data suggest that oxidative stress by cysteamine can be synergistic with the conditioning heat treatment at 44 degrees C which induces thermotolerance. At 37 degrees C, cysteamine itself induces thermotolerance and the enhanced synthesis of heat shock proteins under these conditions.

Adaptation, Physiological↗
PubMed1987

Lack of effect of thermotolerance on radiation response and thermal radiosensitization of murine bone marrow progenitors.

We studied X-ray response, thermal radiosensitization, and time sequencing between heat and radiation for nontolerant and thermotolerant murine bone marrow cells. Survival curves of colony-forming units of granulocyte-macrophages (CFU-GM) have a D0 value of 1.26 +/- 0.04 Gy when irradiated in vivo. Heating at 44 degrees C for 30 min immediately prior to X-ray yields a D0 value of 0.96 Gy, with a thermal enhancement ratio of 1.3. Similar D0 and thermal enhancement ratio values were seen for thermotolerant cells. In vitro experiments with CFU-GM gave similar results. Studies of the effect of time sequence on heat and radiation indicate that for CFU-GM, the interaction between the two modalities do not fully disappear when given within 180 min of each other. Colony-forming units of erythrocytes (CFU-E) irradiated in vivo shows a D0 value of 1.1 +/- 0.03 Gy for radiation alone. Heating at 44 degrees C for 25 min prior to irradiation gives a D0 value of 0.95 Gy (thermal enhancement ratio, 1.1). Again, there was no change in the D0 value of radiation alone or the combination of heat and radiation in thermotolerant CFU-E. Both radiation killing and thermal radiosensitization were the same for thermotolerant and nontolerant CFU-GM and CFU-E.

Animals↗
PubMed1987

Hyperthermic enhancement of cell killing by mitomycin C in mitomycin C-resistant Chinese hamster ovary cells.

The interaction of hyperthermia and mitomycin C (MMC) was studied in wild-type Chinese hamster ovary cells and in Chinese hamster ovary cells selected for resistance to MMC. Hyperthermic potentiation of MMC activity was maximal if heating was done simultaneously, or up to 3 h following MMC exposure. Heat enhanced the effect of MMC in both drug-sensitive and -resistant cells. Dose enhancement ratios increased from 1.3-2.0 at 42 degrees C to 2.6-3.8 at 43.5 degrees C and were similar for all cell lines. Cellular uptake of MMC was determined by high pressure liquid chromatography. MMC uptake was similar in the drug-sensitive and -resistant cell lines at 37 degrees C. Hyperthermia (43.5 degrees C) increased cellular uptake of MMC by 78 and 27% in MMC-sensitive and -resistant cell lines. MMC-resistant cells were more sensitive to heat alone at 42, 43, and 44 degrees C. The results suggest that tumor cells that have developed resistance to MMC might be treated effectively with MMC combined with heat to augment the response to MMC. Resistance to MMC may also render tumor cells more sensitive to hyperthermia.

Animals↗
PubMed1987

Effect of drug exposure duration and sequencing on hyperthermic potentiation of mitomycin-C and cisplatin.

The effects of drug exposure duration and of heat and drug sequencing on hyperthermic potentiation of mitomycin-C (MMC) and cisplatin (DDP) were studied. Heating for 1 h at 42 degrees C was combined with drug exposure times of 1, 2, 4, or 8 h. For both DDP and MMC, hyperthermic potentiation was greatest when heating was done during drug exposure. Dose enhancement ratios for both drugs at 1% survival were highest with the shortest drug exposure times and decreased as the drug exposure time increased from 1 to 8 h. For DDP, the dose enhancement ratio decreased from 1.9 with a 1-h drug exposure to 1.2 with an 8-h drug exposure. For MMC, the dose enhancement ratio decreased from 1.8 to 1.5 as the drug exposure duration was increased from 1 to 8 h. Our results suggest that thermochemotherapy in vivo is likely to be most effective with rapid infusions of DDP or MMC.

Animals↗
PubMed1987

Hydrogen peroxide or heat shock induces resistance to hydrogen peroxide in Chinese hamster fibroblasts.

Survival after H2O2 exposure or heat shock of asynchronous Chinese hamster ovary cells (HA-1) was assayed following pretreatment with mildly toxic doses of either H2O2 or hyperthermia. H2O2 cytotoxicity at 37 degrees C, expressed as a function of mM H2O2 was found to be dependent on cell density at the time of treatment. The density dependence reflected the ability of cells to reduce the effectiveness of H2O2 as a cytotoxic agent. When the survival data were plotted as a function of mumoles H2O2/cell at the beginning of the treatment, survival was independent of cell density. Cells pretreated with 0.1 mM (3-5 mumoles/cell X 10(-7)) H2O2 for 1 hr at 37 degrees C (30-50% survival) became resistant to a subsequent H2O2 treatment 16-36 hr after pretreatment [dose modifying factor (DMF) at 1% isosurvival = 4-6]. Their resistance to 43 degrees C heating, however, was only slightly increased over controls 16-36 hr following pretreatment (DMF at 1% isosurvival = 1.2). During this same interval, the synthesis of protein migrating in the 70 kD region of a one-dimensional SDS-polyacrylamide gel was enhanced twofold in the H2O2-pretreated cells. When the cells were heated for 15 min at 45 degrees C (40-60% survival), the survivors became extremely resistant to 43 degrees C heating and somewhat resistant to H2O2 (DMF at 1% isosurvival = 2). The heat-induced resistance to heat developed much more rapidly (reached a maximum between 6 and 13 hr) following pretreatment than the heat-induced resistance to H2O2 (16-36 hr). The enhanced synthesis of 70 kD protein after heat shock was greater in magnitude and occurred more rapidly following preheating than following H2O2 pretreatment. The cells that became resistant to H2O2 by either pretreatment (H2O2 or heat shock) also increased their ability to reduce the H2O2 cytotoxicity from the treatment medium beyond that of the untreated HA-1 cells. This may be one of the mechanisms involved in the increased resistance and a common adaptive mechanism induced by both stresses. These data indicate that mammalian cells develop resistance to H2O2 following mild pretreatment with H2O2 or heat shock. The cross-resistance induced by H2O2 and heat shock reinforce the hypothesis that some overlap in mechanisms exist between the cellular responses to these two stresses. However, the failure of H2O2 pretreatment to induce much resistance to heat indicates that there are also differences in the actions of the two agents.

Animals↗
PubMed1987

Effect of cisplatin resistance on cellular radiation response.

Cisplatin-resistant tumors of the head and neck are generally resistant to irradiation. To determine whether the association between cisplatin (DDP) resistance and radiation resistance is a cellular phenomenon, we developed DDP-resistant Chinese hamster fibroblasts and studied their response to radiation. DDP resistance did not confer cross resistance to radiation. DDP-resistant cells did not demonstrate altered ability to repair sublethal or potentially lethal radiation damage. However, an isodose concentration of DDP did not inhibit repair of radiation damage in drug-resistant cells as readily as it did in drug-sensitive cells. The results suggest that cross resistance of tumors between DDP and radiation may be a result of the tumor microenvironment, rather than being a cellular phenomenon. Additionally, DDP may not inhibit the repair of radiation damage in DDP-resistant tumors.

Animals↗
PubMed1987

Heat shock proteins: role in thermotolerance, drug resistance, and relationship to DNA topoisomerases.

The events following a mild heat exposure to cells that appear to be closely linked are: enhanced synthesis of hsp's and thermotolerance. In some cases, thermotolerance is also associated with drug resistance. We have recently examined the role that DNA topoisomerase II may play in the induction of these phenomena. VM-26 was found to both initiate hsp synthesis and to cause thermotolerance. Furthermore, the permanent heat resistant or transient thermotolerant cells were more resistant to VM-26 than controls. These results suggest that topoisomerase II, or more likely topoisomerase II-DNA complexes, are affected by heat or by VM-26 in a phenomenologically overlapping manner. Elevated levels of hsp's apparently protect cells against the cytotoxic action of both heat and VM-26.

Animals↗
PubMed1987

Influence of temperature on the development and decay of thermotolerance and heat shock proteins.

The development of thermotolerance and its decay in plateau-phase Chinese hamster cells are shown to be temperature-dependent phenomena. Development of tolerance, after an initial dose of 10 min at 45 degrees C, is appreciably slower between 20 and 28 degrees C than it is at 37 degrees C. Decay of tolerance is also slower in that temperature range; at 4-23 degrees C, it does not decay at all during the 96-h interval of the experiment. At 41 degrees C, thermotolerance decay, "step-down" cell killing, and thermotolerance induction apparently all occur and affect cell survival. The decay of HSP 70 mirrors that of thermotolerance, except at 41 degrees C. At that temperature very likely de novo synthesis of that protein becomes important in determining protein concentration. Our data show that care must be taken when extrapolating from kinetic data obtained with surface tissues in vivo to those in depth. The former are usually at a temperature between 25 and 32 degrees C; the latter are at 37 degrees C.

Adaptation, Physiological↗
PubMed1987

Protection of Chinese hamster ovary cells from heat killing by treatment with cycloheximide or puromycin: involvement of HSPs?

Cycloheximide (CHM) or puromycin (PUR) added for 2 h before heating at 43 degrees C followed by either PUR or CHM during heat greatly protected cells from heat killing. This protection increased with inhibition of protein synthesis. Since treatment with a drug both before and during heating was required for heat protection, and since one drug could be exchanged for the other after the 2-h pretreatment without affecting the heat protection, a common mode of action involving inhibition of protein synthesis is suggested for the two drugs. Drug treatment reduced the synthesis of heat-shock proteins (HSPs) as studied by one-dimensional gel electrophoresis by 80-98% relative to 37 degrees C untreated controls. Synthesis of large molecules (greater than 30 kDa) was preferentially inhibited by PUR but not by CHM. Also for CHM, but not for PUR treatment, a 42 kDa band appeared along with a great reduction in the 43 kDa actin band during CHM treatment at both 37 and 43 degrees C. Furthermore, during CHM or PUR treatment, incorporation of [35S]methionine into HSP families 70, 87, or 110 was not increased relative to incorporation into total protein. However, synthesis of the 70 kDa HSP family was selectively suppressed when cells were incubated at 37 degrees C after CHM treatment, but when cells were incubated at 37 degrees C after treatment at 43 degrees C with CHM, synthesis of the 70 kDa HSP family resumed. When cells were labeled for 3 days, there was no preferential accumulation or turnover of HSP families during heating with or without CHM. Therefore, heat protection caused by treatment with CHM or PUR apparently involves a common mode of action not associated with changes in either total levels or synthesis of HSP families during drug treatment before and during heating. The significance of the changes observed in the synthesis of the HSP 70 family after heat is unknown. As thermotolerance developed during 5 h at 42 degrees C without drugs, synthesis of HSP families 70, 87, and 110, as studied with one-dimensional gels, increased 1.4-fold relative to synthesis of total protein, but compared to HSP families in cells labeled for 5 h at 37 degrees C incorporation was reduced by 40%. The increase of unique HSPs, if studied with two-dimensional gels, would probably be much greater.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Biological↗
PubMed1986

Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts.

We have investigated the effect of heat, radiation or Adriamycin (ADR) on Chinese hamster fibroblasts (HA-1), their heat resistant variants, and their ADR resistant variants. Heat or ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. Cells selected for ADR resistance were not cross resistant to heat and they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing treatment protocols involving combined modality trials.

Animals↗
PubMed1986

Chemically induced resistance to heat treatment and stress protein synthesis in cultured mammalian cells.

Short exposure (1-2 h) of cultured cells, derived from a transplantable murine mammary carcinoma, to sodium arsenite, 2,4-dinitrophenol (DNP), carbonylcyanide-3-chlorophenylhydrazone (CCP) or disulfiram, induced resistance to a subsequent heat treatment, similar to heat-induced thermotolerance. Optimum resistance to a test heat treatment of 45 min at 45 degrees C after sodium arsenite exposure was obtained at a concentration of 300 microM, after DNP exposure at 3mM, after CCP at 300 microM and after disulfiram exposure in the range 1-30 microM. Exposure of cells to CCP, sodium arsenite or disulfiram led to enhanced synthesis of some proteins with the same molecular weight as 'heat shock' proteins. The pattern of enhanced synthesis of these proteins was agent specific. We could not detect significantly enhanced synthesis of the proteins after DNP using one-dimensional gel electrophoresis. These results suggest that enhanced stress protein synthesis is not a prerequisite for the development of thermal resistance.

2,4-Dinitrophenol↗
PubMed1986

Hyperthermic potentiation of cis-diamminedichloroplatinum(II) cytotoxicity in Chinese hamster ovary cells resistant to the drug.

The cytotoxic and pharmacological properties of hyperthermia and cis-diamminedichloroplatinum(II) (DDP) were studied in DDP-sensitive and DDP-resistant Chinese hamster ovary cells in vitro. Cytotoxicity was measured by cell survival using colony formation assay and cellular platinum levels were determined by atomic absorption spectrophotometry. Hyperthermia potentiated DDP cytotoxicity in both DDP-sensitive and DDP-resistant Chinese hamster ovary cells. Dose enhancement ratios increased from 1.4 to 6.5 over the temperature range of 39-43 degrees C. Cellular accumulation of platinum at 37 degrees C in the sensitive cells was 2.3- to 3.3-fold greater than that in the drug-resistant cells. Cellular accumulation of DDP was increased by factors of 1.5 and 2.2 at elevated temperature. DDP resistance did not confer cross-resistance to heat alone. The results suggest that hyperthermia could be used to circumvent DDP resistance.

Animals↗
PubMed1986

Lack of development of thermotolerance in early progenitors of murine bone marrow cells.

We have studied the sensitivities of four hematopoietic stem cell types to heat stress as well as their abilities to develop thermotolerance. Granulocyte-macrophage colony forming units were the most heat resistant bone marrow progenitors tested. Of the erythroid progenitors tested, erythrocyte colony forming units were more resistant than the two more primitive erythrocyte burst forming units. To determine their ability to develop thermotolerance, hematopoietic precursors were heated in vivo at 43 degrees C for 30 min. At various times thereafter the hematopoietic stem cells were flushed from female C3Hf/Sed mouse preheated tibia. The bone marrow cell suspensions were then heated in vitro and plated for colony formation. The four stem cell precursors differed markedly in their abilities to develop thermotolerance. The thermotolerance induced in granulocyte-macrophage colony forming units reached a maximum at 3-6 h after heating and disappeared by 24-48 h. The thermotolerance in erythrocyte colony forming units (0.5 units erythropoietin/ml media) reached a maximum at 3-6 h and disappeared by 48-72 h. The maximum level of thermotolerance reached by granulocyte-macrophage colony forming units and erythrocyte colony forming units was approximately the same. On the contrary, the two more primitive erythrocyte precursors which were grown by the addition of 2.5 and 5 units erythropoietin/ml of media do not develop thermotolerance.

Animals↗
PubMed1986

Cellular glutathione, thermal sensitivity, and thermotolerance in Chinese hamster fibroblasts and their heat-resistant variants.

HA-1 Chinese hamster fibroblasts and two heat-resistant variants, designated 2242 and 3012. have been investigated to determine the role that glutathione (GSH) plays in intrinsic cellular resistance to heat and in the development of thermotolerance. The constitutive levels of GSH did not correlate with intrinsic heat sensitivities, but depletion of GSH sensitized all three cell lines to thermal stress. After heating (43.5 degrees C/2 h), surviving fractions were 1 X 10(-3), 1 X 10(-2), and 8 X 10(-3) for HA-1, 2242, and 3012 cells, respectively. Depletion of cellular GSH with L-buthionine-S, R-sulfoximine to less than 10% of control values sensitized such that the thermal responses of these three cell lines were nearly indistinguishable at 43.5 degrees C. Surviving fractions were 2 X 10(-4), 1 X 10(-4), and 1 X 10(-4) for L-buthionine-S,R-sulfoximine-treated HA-1, 2242, and 3012 cells, respectively, following heating at 43.5 degrees C for 2 h. The development of thermotolerance in HA-1 cells following heat shock (45 degrees C/15 min) was unaffected by the inhibition of GSH synthesis. On the other hand, when GSH levels were maintained at extremely low levels, the development of thermotolerance was inhibited. In addition, following heat shock, cellular GSH was decreased and remained below control levels during the development of thermotolerance.

Animals↗