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At least 1,693 records · Page 94Linked to original sources
PubMed1990

Effect of host age upon interleukin-2-mediated anti-tumor responses in a murine fibrosarcoma model.

The age-associated decline in immune function may be an important factor in both the pathogenesis of neoplastic diseases and the response to immunopharmacological therapies. With the increased efforts to develop immunotherapy with such agents as interferon and interleukin-2 (IL-2), the question of the effect of host age upon response is of practical importance. Phase I and phase II clinical trials of IL-2 have included primarily young patients, and toxicity and efficacy have not been reported with specific reference to host age. In this study, we examined young and old mice with regard to in vitro natural killer and lymphokine-activated killer (LAK) cell functions. We also assessed the effects of exogenously administered recombinant human IL-2 in tumor-bearing mice of various ages. We found that natural killer cell function was demonstrably lower in old mice but that LAK cell function was comparable (young versus old). Furthermore, IL-2 treatment was successful in increasing survival time in old mice, similar to results in young mice. Our observations allow the prediction that immune senescence per se does not preclude successful anti-neoplastic treatment with IL-2.

Aging↗
PubMed1991

The improved effects of specific active immunotherapy on a rat fibrosarcoma by antitumor drugs.

We have tried to find out if the combination of a xenogenized tumor cell vaccine and antitumor drugs is able to induce a synergistic increase in the antitumor therapeutic effect. The degree of increase in the LTD50 (50% lethal tumor dose) is expressed numerically, as a quantitative index designed to compare degrees of transplantation resistance to tumor cell challenge. A LTD50 was achieved by an intradermal (i.d.) immunization with xenogenized tumor cells when challenged with tumor cells implanted intraperitoneally 2 weeks after the immunization: this LTD50 value was 527,000 times higher than that of the non-immunized group. When we combined this type of immunization with appropriate doses of bleomycin (BLM) or cyclophosphamide (CY), which are able to augment antitumor immunity, the LTD50 was 723,000-1,190,000 times higher than that of the non-immunized group. This increase in the LTD50 is definitely higher than that achieved by a single immunization with irradiated tumor cells (x 33,000) and combined with either BLM (x 93,000) or CY (x 140,000). We also studied the therapeutic effect of a tumor cell vaccine combined with antitumor drugs BLM or CY in tumor-bearing rats. We observed a synergistic effect caused by BLM or CY after i.d. immunization with xenogenized tumor cells: this showed a significant increase when compared with the therapeutic effects obtained by chemotherapy alone (P less than 0.01). Nevertheless, there was no evidence that the above antitumor effects is superior to the effect achieved by irradiated tumor cells.

Animals↗
PubMed2006

Elevation of radiolabelled thymidine uptake in RIF-1 fibrosarcoma and HT29 colon adenocarcinoma cells after treatment with thymidylate synthase inhibitors.

PURPOSE: We recently showed an increase in tumour uptake of 2-[(11)C]thymidine in patients with gastrointestinal malignancies after thymidylate synthase (TS) inhibition. To understand the phenomenon in more detail, we investigated whether TS inhibition by different TS inhibitors leads to a dose- and time-dependent change in the uptake of radiolabelled thymidine, and whether radiotracer uptake is related to changes in cell viability resulting from treatment. METHODS: RIF-1 and HT29 cells were treated with the TS inhibitors 5-fluorouracil (5-FU) and AG337 (nolatrexed dihydrochloride), as well as cisplatin as control. The cell viability and net accumulation of [(3)H]thymidine after a 1-h pulse was determined at different times after drug treatment. RESULTS: In both cell lines, [(3)H]thymidine uptake increased after a 2-h treatment with 5-FU, in a dose- and time-dependent manner. [(3)H]thymidine uptake decreased at 24 and 48 h post treatment. AG337 also produced a similar effect. In contrast to the TS inhibitors, cisplatin decreased [(3)H]thymidine uptake in RIF-1 and HT29 cells at all time points. Cell viability was compromised only after 24 h. CONCLUSION: Using two types of TS inhibitor, we have shown an increase in [(3)H]thymidine uptake, in a dose-dependent manner, a few hours after TS inhibition when the cell viability was not compromised. This effect was not seen with a non-TS inhibitor. These findings suggest that 2-[(11)C]thymidine positron emission tomography can be used to study TS inhibition in vivo at early time points when cell viability is not compromised and may therefore be helpful in the development of new TS inhibitors and in differentiating between patients with tumours sensitive to TS inhibitors and those unlikely to respond.

Adenocarcinoma↗
PubMed1995

[Colon carcinoma simulating retroperitoneal inflammatory pseudotumor. Case report of so-called abdominal inflammatory fibrosarcoma].

Resection of a stenosing colon tumor in an 89-year-old male patient led to the diagnosis, unusual at this age, of an inflammatory pseudotumor (synonym: plasma cell granuloma) of the retroperitoneum and mesentery, which invaded the large bowel and showed infiltration of one regional lymph node. Histology and immunohistochemistry (demonstrating a myofibroblastic phenotype of the proliferating spindle cells and polyclonality of abundantly present plasma cells) of the specimen resembled previously reported lesions in various locations. The etiology and exact nosological classification of inflammatory pseudotumors are not yet unequivocally settled. The recently published conjecture that such lesions of the retroperitoneum represent a separate entity with features of a malignant neoplasm is discussed.

Aged↗
PubMed1998

Cell surface and nuclear changes during TNF-alpha-induced apoptosis in WEHI 164 murine fibrosarcoma cells. A correlative light, scanning, and transmission electron microscopical study.

Tumour necrosis factor (TNF)-alpha-induced apoptosis is associated with several nuclear and cell surface alterations, in particular with the condensation of chromatin and the fragmentation of the cell nucleus, formation of blebs on the cell surface and breakdown of the plasma membrane. However, there is little information about the relationship between the cell surface alterations and the nuclear changes during apoptosis. To study this, cultured WEHI cells were exposed to TNF-alpha over different time periods. The cytological changes were studied using a correlative approach, which allowed observation of the same cell consecutively under light, scanning and transmission electron microscopy. The earliest sign of cell alteration was a reduction of the number of microvilli after 15 min of TNF-alpha exposure. This reaction was reversible (reappearance of microvilli) and took place during the first hour, in which neither nuclear alterations nor plasma membrane breakdown were observed. The changes in the nucleus began with condensation of chromatin after approximately 1 h of TNF-alpha-exposure. After 4-5 h the microvilli disappeared again, particularly in areas where the formation of blebs (blebbing) was observed. Strikingly, cell surface alterations (bleb formation) were detected only in those cells that presented with condensed chromatin, and not in cells with a normal chromatin pattern, proving at least a close correlation between nuclear and cell surface changes during the process of apoptosis.

Animals↗
PubMed2006

Inhibitory effect of chitooligosaccharides on matrix metalloproteinase-9 in human fibrosarcoma cells (HT1080).

Matrix metalloproteinase-9 (MMP-9) has gelatinase activity and plays an important role in cancer invasion and metastasis. Therefore, inhibition of specific types of MMPs including MMP-9 has become an attractive target for therapeutic intervention. The aim of this study was to investigate the effect of chitooligosaccharides (COS) on activity and expression of MMP-9 in HT1080 cells. The inhibitory effect of COS with different molecular masses was examined by gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), gene reporter assay, and Western blot analysis. MMP-9 inhibition in the presence of COS was clearly observed in gelatin zymography. Specifically, 1- to 3-kDa COS (COS-I) exhibited the highest inhibitory effect on MMP-9 activity in HT1080 cells among tested molecular mass fractions. It was also found that COS-I was capable of inhibiting both gene and protein expression of MMP-9 (P<0.01). These results suggest that low molecular mass COS can be considered as a potent inhibitor of MMP-9.

Cell Line, Tumor↗