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PubMed2003

Effects of adenosine on the growth of murine G:5:113 fibrosarcoma cells in vitro.

It has been observed that adenosine suppresses the growth of G:5:113 murine fibrosarcoma cells in vitro with EC50 of 178 mM. Changes in the cell cycle including decreased percentage of cells in S-phase, increased portion of cells in G0/G1-phase, as well as prolonged generation time were found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, enhanced the growth suppression induced with adenosine in concentrations of 100 and 200 microM. It follows from these results that the action of adenosine on the G:5:113 cells is extracellular, mediated by adenosine receptors. Elevation of extracellular adenosine might serve potentially as an anticancer therapeutic agent.

Adenosine↗
PubMed2002

Transcription factor Egr-1 activates collagen expression in immortalized fibroblasts or fibrosarcoma cells.

Synovial fibroblasts from rheumatoid arthritis patients express elevated levels of the transcription factor Egr-1. The metabolic consequences of Egr-1 overexpression in fibroblasts are not known in detail. Therefore we searched for gene products that are differentially expressed in Egr-1(high) versus Egr-1(low) fibroblasts. Immortalized synovial fibroblasts were transfected with two different Egr-1 expression vectors. Expression of recombinant Egr-1 was confirmed by RT-PCR and immunoblots. Random arbitrarily primed PCR revealed that Egr-1 induces enhanced transcription levels of the alpha1 chain of type I collagen. Increased expression of the alpha2 (I) chain could also be observed. We found enhanced levels of type I collagen propeptide in supernatants and stronger signals of alpha2 (I) protein in extracts of the Egr-1(high) expressing clone versus controls. Additionally, Egr-1 was transiently expressed in fibrosarcoma cells. These cells showed a pronounced elevation of type I collagen (alpha1) transcripts as well. Moreover, we could demonstrate that Egr-1 induces transcription of other genes including type II collagen (alpha1) and plateled-derived growth factor beta1. These data suggest that upregulation of Egr-1 might contribute tofibrosis observed in rheumatoid arthritis synovium by activation of genes encoding the alpha1 and alpha2 chains of type I collagen.

Cloning, Molecular↗
PubMedDate not supplied

Effect of tumour regression on serum and tissue copper concentration in mice bearing induced fibrosarcoma.

Serum and tissue copper concentration was determined in mice bearing induced fibrosarcoma after successful chemotherapeutic treatment. The results showed a significant depression in copper concentration in the serum and tumour tissue after treatment with anti-cancer drugs. However, the liver copper concentration showed no significant change in treated groups of mice compared to before treatment.

Animals↗
PubMed1990

Hematological changes in the mice transplanted with methylcholanthrene-induced fibrosarcoma.

Hematological values of the peripheral blood in the mice transplanted with methylcholanthrene-induced fibrosarcoma were examined. Values for red blood cells and platelets reduced after tumor transplantation. Values for white blood cells increased with the percentage of neutrophils being increased significantly. Phagocytic activity of neutrophils from the tumor-bearing mice was not reduced. The cultured fluid of the tumor used in the experiments possessed strong colony stimulating activity to bone marrow cells.

Animals↗
PubMed1993

Vascular architecture of 3-methyl choranthrene-induced rat fibrosarcoma demonstrated by scanning electron microscopy of resin casts.

A detailed knowledge of the vascular system of tumors is requisite to a clear understanding of tumor physiology and pathology. Accordingly, in this study, examination was made of the vascular architecture of rat fibrosarcomas induced by 3-methyl choranthrene by scanning electron microscopy of resin casts to observe the three-dimensional vascular pattern of the sarcoma. The results were compared with those of corresponding serial sections of India ink-injected tissue. The major arteries in and around tumors appeared devoid of intra-arterial cushions which regulate blood flow. The arterial lining of resin casts was smooth just at the site where it entered the tumor. This may possibly be indication of degeneration and loss of the smooth muscle layer in the vascular wall. Casts of capillaries were very thin from 4 to 6 microns in diameter and very few sprouts could be seen. Capillaries, frequently present in superficial regions of the tumor, formed a rich irregular fine polygonal network. In fibrous tissue in deeper regions of the tumor, this network was coarse. The absence of intra-arterial cushions and degeneration of muscle cells may thus possibly be the reason for the characteristic haemodynamics of tumors.

Animals↗
PubMed2001

Investigation of cross-resistance to a range of photosensitizers, hyperthermia and UV light in two radiation-induced fibrosarcoma cell strains resistant to photodynamic therapy in vitro.

Two distinct photodynamic therapy-resistant variants of the murine radiation-induced fibrosarcoma (RIF) cell line have been isolated. One strain displayed relative resistance over the parental RIF-1 strain to treatment with the porphyrin-based compound, polyhaematoporphyrin (PHP), whereas the other strain displayed relative resistance over the RIF-1 strain to treatment using the cationic zinc (II) pyridinium-substituted phthalocyanine (PPC). The PHP-resistant strain did not display cross-resistance to PPC-mediated treatment, and vice versa. In both PDT-resistant strains, the increased resistance could not be attributed to altered cellular growth rate, antioxidant capacity or intracellular sensitizer localization. The PHP-resistant strain displayed resistance to treatment with both short (1 h) and extended (16 h) sensitizer incubation periods, which may indicate that in this strain, the resistance has arisen through an alteration in a membrane component. Conversely, the PPC-resistant strain only displayed increased resistance over the parental cells to treatment involving the short drug incubation, which is likely to reflect the existence of a threshold effect caused by the alteration of an individual cellular target. Each resistant strain has been compared to the parental strain in terms of cellular sensitivity to treatment with a range of other photosensitizers, hyperthermia, UV light and the anticancer agent cis-diamminedichloroplatinum. The PHP-resistant strain exhibited crossresistance to photosensitization treatment using exogenously added protoporphyrin IX, and also to treatment with the anionic phthalocyanine sensitizers, zinc (II) tetrasulfonated phthalocyanine and zinc (II) tetraglycine-substituted phthalocyanine. The PPC-resistant strain did not display cross-resistance to any of the treatment strategies employed in this investigation. The results of this investigation indicate that there are at least two distinct mechanisms of PDT resistance in RIF cells, and that the mechanism of PHP resistance may, to some extent depend, upon the physical nature of the sensitizer molecule.

Animals↗
PubMed2003

Potentiation of photodynamic therapy with hypericin by mitomycin C in the radiation-induced fibrosarcoma-1 mouse tumor model.

Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been shown to be a promising photosensitizer. We investigated the combination of hypericin-photodynamic therapy (PDT) and a bioreductive drug mitomycin C (MMC) in the present study. The radiation-induced fibrosarcoma-1 tumors were exposed to laser light (120 J/cm2 at 595 nm) 24 h after an intravenous injection of hypericin (1 mg/kg). Hypericin-PDT alone significantly decreased tumor perfusion and oxygen tension as demonstrated by India ink staining technique and OxyLite pO2 measurement, respectively. The in vivo-in vitro cell-survival assay revealed about 60% direct tumor cell killing immediately after PDT. No significant delayed tumor cell death was observed after PDT, which suggests that vascular damage does not contribute significantly to the overall tumor cell death. Injection of a 2.5 mg/kg dose of MMC 20 min before light application significantly decreased tumor cell survival and delayed tumor growth compared with PDT or MMC alone. No greater skin reaction was observed after the combination of MMC and PDT than after PDT alone. Our study demonstrates that combining hypericin-PDT with MMC can be effective in enhancing tumor response with little side effect.

Animals↗
PubMed2003

Advances in the adjuvant treatment of infantile fibrosarcoma.

Infantile fibrosarcoma is a rare soft tissue tumor, predominately affecting young infants. It grows rapidly and is locally infiltrative but rarely metastases. Complete surgical removal is usually curative but is impossible in some patients and would result in significant functional or cosmetic consequences in many others. Neoadjuvant chemotherapy will cause many tumors to shrink significantly, allowing less mutilating surgical resections to be performed--this is the current recommendation where immediate surgical removal cannot be accomplished without unacceptable morbidity. In contrast, there is no defined role for adjuvant chemotherapy or radiation following complete surgical resection. Although there is a significant risk of local recurrence, most of these can be successfully treated with further surgery and the overall survival rate exceeds 90%.

Chemotherapy, Adjuvant↗
PubMed2006

The response of RIF-1 fibrosarcomas to the vascular-disrupting agent ZD6126 assessed by in vivo and ex vivo 1H magnetic resonance spectroscopy.

The response of radiation-induced fibrosarcoma 1 (RIF-1) tumors treated with the vascular-disrupting agent (VDA) ZD6126 was assessed by in vivo and ex vivo 1H magnetic resonance spectroscopy (MRS) methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho) in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS) and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2) of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.

Animals↗
PubMed1992

The difference in immunological properties between lymph node metastatic and non-metastatic cell lines of MCA-induced fibrosarcoma of C4W mice.

To pursue the process of lymph node metastasis, i.e, the preferential tumor growth in lymph node, we have established the non-metastatic M2B cell line which was derived from 3-methylcholanthrene-induced fibrosarcoma of C4W mouse and a metastatic cell line, M2BLN-M+ which was obtained from metastatic lymph nodes of irradiated C4W mouse which was subcutaneously implanted with cultured tumor cells, because implanted tumor cells were derived from the spontaneous metastatic lymph node of the parental M2B tumor, but regressed in naive C4W mouse. We examined the characteristics of both tumor cell lines in terms of the immunological cellular interactions. M2BLN-M+ showed unexpectedly to be more susceptible to cytotoxicity of immune effectors (NK cell, macrophage and cytotoxic T lymphocyte) than M2B did. When cultured both tumor cells with these effector cells, the growth inhibition of M2BLN-M+ was greater than that of M2B. The regional lymph node of tumor-bearer, however, showed no effective cytotoxic activity as reported by others. On the contrary, when cultured both tumor cells with non-immune lymph node cells, to be surprised, the proliferation of M2B was markedly suppressed, while that of M2BLN-M+ was slightly inhibited. The lymph node cells of M2B-bearing mice showed stronger cytostatic activity to M2B. The results suggest that the cytostatic activity of lymph node cells will be a pivotal factor, concerning the establishment of lymph node metastasis.

Animals↗
PubMed2004

Fibrosarcoma of the brood pouch in an aquarium-reared lined seahorse (Hippocampus erectus).

An adult, male, captive lined seahorse (Hippocampus erectus) was presented with weight loss, anorexia, and brood pouch distention. Initial treatments included manual expression of the brood pouch followed by saline flushes and enrofloxacin infusions. Radiographs and physical examination identified a nodular swelling in the brood pouch wall. The mass was excised, but the seahorse died. Necropsy and histopathology revealed a malignant mesenchymal tumor with a collagenous stroma, and a brood pouch fibrosarcoma was diagnosed.

Animals↗
PubMed2003

Similar radiation sensitivities of acutely and chronically hypoxic cells in HT 1080 fibrosarcoma xenografts.

It has been suggested that chronically hypoxic tumor cells may be more radiosensitive than acutely hypoxic or even aerobic cells. In the present study we have used the fact that chronically, but not acutely, hypoxic cells that are transformed with a vector containing an enhanced green fluorescent protein (EGFP) driven by a hypoxia-responsive promoter become green (high EGFP) at low oxygen concentrations and can be viably sorted from transplanted tumors in vitro. We showed that the fluorescence of HT 1080 human fibrosarcoma cells stably transfected with this vector increases constantly with decreasing O2 concentrations (<2%, longer than 1 h, half maximum approximately 0.2% for longer than 8 h), and that cells subjected to repeated cycles of hypoxia/reoxygenation (simulating acutely hypoxic cells) showed only background fluorescence. To test the radiosensitivity of acutely and chronically hypoxic cells in tumors, we isolated high-EGFP ("chronically hypoxic") and low-EGFP cells (containing both acutely hypoxic and aerobic cells) from HT 1080 xenograft tumors by fluorescence-activated cell sorting (FACS), immediately after in situ treatment with 20 Gy (ambient or clamped), and plated the cells to determine clonogenic survival in vitro. We found that the survival of high-EGFP cells after irradiation was not affected by clamping, suggesting that all, or almost all, of these cells were fully (chronically) hypoxic. Also, the survival of the low-EGFP cells irradiated under clamped conditions (acutely hypoxic cells) was not significantly different from that of the high-EGFR cells (chronically hypoxic) cells irradiated under nonclamped (or clamped) conditions. We therefore conclude that, at least in this tumor model, the radiation sensitivity of chronically hypoxic cells is similar to that of the acutely hypoxic cells.

Animals↗
PubMed1990

Effect of selected splenic irradiation on growth of meth A-fibrosarcoma in mice and partial characterization of splenic effector and suppressor cell populations.

Meth A-fibrosarcoma bearing BALB/c mice were subjected to selected splenic irradiation (2.0-4.0 Gy) on days 7 and 14 of tumor growth. Tumor growth was recorded by serial measurement. Irradiation given on day 7 caused regression of tumor, but irradiation given on day 14 did not show tumor regression. Antitumor activity in the Winn assay was detected in spleen cells 3 days after irradiation, but was not detected 7 days after. The cell surface phenotypes were analyzed on days 3, 7 and 14 of splenic irradiation using monoclonal antibodies (anti-Thy1.2 antibody, anti-Lyt1 antibody, anti-Lyt2 antibody, anti-L3T4 antibody) by flow cytometry. Thy 1.2, Lyt1, and L3T4 cells were increased on day 3 of splenic irradiation, but were not on days 7 and 14. Lyt2-cells did not show increase on days 3, 7 and 14. It was possibly suggested that selected splenic irradiation induced tumor regression was caused by the ability of irradiation to preferentially eliminate suppressor T cells, thereby allowing effector T-cells to become relatively dominant.

Animals↗
PubMed1993

IGF-II producing hepatic fibrosarcoma associated with hypoglycemia.

A 67-year-old male was admitted with the complaint of weakness at hunger early in the morning, when blood glucose was less than 40 mg/dl. The abdominal ultrasonogram and computerized tomogram demonstrated a huge tumor in the right liver lobe. Hypoglycemia disappeared after transcatheter arterial embolization. Then hepatic lobectomy was performed. The tumor was histologically shown to be a fibrosarcoma. Insulin-like growth factor-II was intensely stained in the Golgi area of the tumor cells, suggesting its role in the mechanism of hypoglycemia.

Aged↗
PubMedDate not supplied

Subrenal capsule assay applied to examine the sensitivity of allogenic mouse fibrosarcoma to hyperthermia, chemotherapeutic drugs or combined treatment.

The thermosensitivity and chemosensitivity of fibrosarcomas of C3H/He mouse were investigated using the subrenal capsule assay with female ICR mice as host. Five typical chemotherapeutic drugs (mitomycin C, adriamycin, 5-fluorouracil, cis-DDplatinum and cyclophosphamide) tested were effective in suppressing tumour growth. Total-body hyperthermia given at 41.5 degrees C for 30 min twice during the 6-day period exerted little effect. However, an interactive effect was found with the combination of hyperthermia and mitomycin C. The combination of hyperthermia with other drugs failed to exhibit an interactive effect, since the effects of the drugs alone were considerable. The potential clinical applicability of this test is discussed.

Animals↗
PubMedDate not supplied

The effect of bleomycin administered in combination with hyperthermia on a C3H mouse fibrosarcoma.

The effect of bleomycin (BLM) on a murine fibrosarcoma, FSa-II, was investigated at elevated temperatures. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Single-cell suspensions of the tumour were transplanted into the murine foot. Tumours with an average diameter of 4 mm were treated in a water bath where a desired temperature was maintained. Some animal groups received an intraperitoneal injection of glucose 60 min before hyperthermia to reduce tumour tissue pH. Hyperthermia was given for 60 min at 41.5 degrees C, 30 min at 43.5 degrees C, or 60 min at 43.5 degrees C, and tumour growth (TG) time to reach 1000 mm3 was studied. BLM treatment at 41.5 degrees C for 60 min prolonged the TG time compared to BLM treatment at a room temperature. The identical prolongation was observed following BLM treatment given at 43.5 degrees C for 30 min, although the growth prolongation was greater following BLM treatment given at 43.5 degrees C for 60 min than the other two treatments. This greater prolongation is probably attributable to an additive effect; namely hyperthermia of 43.5 degrees C for 60 min induces substantial lethal damage by itself while the other two heat treatments do not induce significant damage. It is interesting to note that this kind of enhancement was observed at a low temperature of 41.5 degrees C. A glucose injection before BLM and hyperthermia treatments further enhanced tumour response. These observations agree with our previous observations following in vitro treatments of the same tumour cells, and indicate that BLM is a good drug to be combined with hyperthermia.

Animals↗
PubMedDate not supplied

The effect of cis-diamminedichloroplatinum(II) treatment at elevated temperatures on murine fibrosarcoma, FSa-II.

The effect of cis-diamminedichloroplatinum(II) (cis-DDP) on the murine fibrosarcoma cells was investigated in vitro and in vivo. For in vitro experiments tumour cell suspensions containing a given amount of cis-DDP were treated in water bath maintained at a desired temperature, and cell survival was determined by the lung colony assay. The D0 or the time to reduce survival from 1.0 to 0.37 on the exponential portion of the survival curve was determined and 1/D0 was plotted as a function of 1/T, where T stands for the absolute temperature. The slope of this Arrhenius plot indicated that the activation energy for chemical reaction of cis-DDP was 44 kcal/M between the temperature range from 37 to 41 degrees C. For in vivo experiments tumours were transplanted into the foot and treated by immersing the animal foot into a water bath when each tumour reached an average diameter of 4 mm (35 mm3). The drug was injected i.p. immediately before hyperthermia. The tumour growth (TG) time or the time required for a tumour to reach 1000 mm3 from the treatment day was determined, and the median TG time was obtained by logit analysis. Dose-response curves between the TG time and drug dose indicated that the cytotoxic effect of cis-DDP was enhanced at elevated temperatures. This enhancement increased with increasing temperature from room temperature to 43.5 degrees C. Because of short plasma half-time of cis-DDP, continuous infusion and pulse injections were attempted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Increased tumour response of a murine fibrosarcoma to low temperature hyperthermia and low dose rate brachytherapy.

The present animal tumour study was carried out to determine the effectiveness of low temperature hyperthermia combined with low dose rate radiation based on the cell culture studies of our laboratory and others that demonstrated a significant radiosensitization obtained by low temperature hyperthermia and low dose rate radiation. Well-oxygenated murine fibrosarcoma Meth-A tumours growing in Balb/c mice were treated with heat (41 degrees C tumour temperature) by immersion of the tumour-bearing leg in a waterbath concurrently with low dose rate radiation. Radiation was delivered using 192Ir interstitial implantation at absolute dose rates of 0.416-0.542 Gy/h. The effect of heat alone on tumour growth and normal tissue was minimal. Tumour growth delay following 30 Gy radiation was 4.9 days. Significant delay in tumour growth was observed with the addition of low temperature hyperthermia delivered concurrently. Enhancement in radiation response was seen with increasing duration of heat treatment; tumour growth delays were 9.5 days following 4 h heat (41 degrees C) treatment and 16 days following 6 h treatment. Three sessions of fractionated hyperthermia 4 h/day during the course of low dose-rate radiation significantly delayed tumour growth to 18.6 days. The results indicate that fractionated heat treatment in conjunction with low dose rate radiation has potential for improving tumour response without adversely affecting normal tissue reaction. This in vivo study represents an extension of the cell culture data and provides further radiobiological basis for the combined use of low temperature hyperthermia and low dose rate radiation.

Animals↗