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  • 1
    ISSN: 1436-2813
    Keywords: human breast carcinoma ; nude mice ; cancer chemotherapy ; endocrine therapy ; hormone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytotoxic and endocrine therapy on a human breast carcinoma (Br-10) serially transplanted into nude mice was given with reference to the sequence of drug administration. Mitomycin C (MMC) was combined with 2.5 mg/kg of tamoxifen (TAM). MMC was dissolved in 0.2 ml of physiological saline and administered intraperitoneally once weekly. TAM was dissolved in 0.1 ml of sesame oil and administered intramuscularly twice weekly. Both drugs were administered in the reverse sequence for 2 or 3 weeks. Cytosol estrogen receptor (ERc), nuclear estrogen receptor (ERn) and progesterone receptor (PgR), and3H-thymidine uptake labeling index (L.I.) were assayed after the treatment. When 1.5 mg/kg of MMC was combined with TAM, statistically significant differences were nil between the different sequential administrations. When the MMC administration was reduced to 0.75 mg/kg and 2 weeks, respectively, the MMC→TAM sequence was more effective than the reversed sequential administration. MMC preserved ERc and depressed L.I. to almost half of that of the control tumor. TAM generated the ER systems and slightly depressed L.I. These different modes of action between MMC and TAM on ER systems and L.I. may explain the antitumor effects of different sequential administrations.
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  • 2
    ISSN: 1436-2813
    Keywords: bromodeoxyuridine ; cell kinetics ; immunohistochemical staining ; monoclonal antibody ; human tumor xenograft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cell kinetics of human tumor xenografts serially transplanted into nude mice was examined using bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody. After various doses of BrdU were given intraperitoneally into tumor bearing nude mice, the tumors were resected and stained immunohistochemically, using the anti-BrdU monoclonal antibody. The number of stained cells was demonstrated as the labeling index (LI). The optimal condition for BrdU staining was assumed to be 300mg of BrdU per kg followed by an incubation period of one hour. Since the LI by BrdU closely correlated with that in autoradiography by3H-TdR, this method is more useful and safer than the conventional autoradiographic study for investigating clinical cell kinetic analysis, as there is no need to use potentially hazardous radioactive compounds and the period of assay is shorter.
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  • 3
    ISSN: 1436-2813
    Keywords: cisplatin ; gastric cancer ; peritoneal carcinomatosis ; sodium thiosulfate ; intraperitoneal chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 μg h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.
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  • 4
    ISSN: 1436-2813
    Keywords: L-leucovorin ; 5-fluorouracil ; human colon carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40–80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.
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  • 5
    ISSN: 1436-2813
    Keywords: human breast carcinoma ; nude mice ; hormone dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tumor cells (0.5 ml, 1×107) of MCF-7 line were inoculated into the subcutaneous tissue or intraperitoneum of female BALB/c nude mice. Primarily tansplanted mice were treated with 17β-estradiol dipropionate (E2) in a dose of 5 mg/kg and 17α-hydroxy progesterone caproate (Pg) in a dose of 250 mg/kg once a week. After the transferable strain was established, tumors were transplanted into female and male mice treated with E2, Pg, and E2+Pg. The tumors treated with E2 or E2+Pg grew exponentially while tumors in the other group regressed. Pg was assumed to play some role in the growth of MCF-7, in the presence of estrogen. Although cytosol estrogen receptors (ERc), nuclear estrogen receptors (ERn), and progesterone receptors (PgR) were detected by dextran coatedcharcoal method and exchange assay in the growing tumors, ERn and PgR of regressing tumors was usually negative. This MCF-7 strain in nude mice may be a promising animal model for studying chemo-hormone therapy for human breast carcinomas.
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  • 6
    ISSN: 1436-2813
    Keywords: in vitro chemosensitivity test ; antitumor effect ; gastrointestinal and lung cancers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The results of two types of in vitro chemosensitivity tests, namely, the human tumor clonogenic assay (HTCA) and the succinic dehydrogenase inhibition assay (SDIA), for solid tumors, including stomach, colorectal and lung cancers, were analyzed and their correlation with clinical effects evaluated. The anticancer agents employed were mitomycin C (MMC), 5-fluorouracil (5-FU), adriamycin (ADM) and cisplatin (DDP). The evaluability rates of the assays were 54.5% for HTCA and 89.0% for SDIA. Among the 29 cases with evaluable lesions subjected to HTCA, there were 4 true positives, 9 false positives, and 16 true negatives, whereas among the 32 cases subjected to SDIA, the corresponding numbers were 2, 6, and 24, respectively. There were no false negatives for either assay, the accuracy of prediction for HTCA being 69.0% and for SDIA, 81.3%. The true positives of both assays included one complete response (CR) and five partial responses (PR), although the eventual outcome was cancer death in all cases. Interestingly, in five out of the six true positive cases, the agent involved was either ADM or DDP, both the which are usually regarded as “second line” anticancer agents for gastrointestinal carcinomas.
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  • 7
    ISSN: 1436-2813
    Keywords: human colon cancer ; metastases ; nude mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract COL-2-JCK, a human colon cancer xenograft line able to be transplanted into nude mice, was implanted in the subserosal layer of the cecum, either as cancer tissue or as a single cell suspension. When cancer tissue was used for the cecal implantation, 100% extensive local tumor growth and a high incidence of metastases to the regional lymph nodes, peritoneum, liver, and lung was observed. In contrast, when the cell suspension of this line was injected into the cecal wall, no metastases were observed, with significantly reduced local tumor growth. The use of cancer tissue maintaining the original cancer tissue structure is therefore considered imperative for allowing full expression of the biological characteristics of cancer cells. This nude mouse model using the cecal implantation of cancer tissue should thus prompt further study on the biology of human colon cancer.
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  • 8
    ISSN: 1436-2813
    Keywords: estrogen ; nude mouse ; hormone dependency ; human breast carcinomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect and mechanisms of 17β-estradiol (E2) on breast cancer cells were studiedin vivo andin vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E2 at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E2 in 3 out of the 4 ER positive tumors, the Td of the E2 treated groups being 17.6 days for MCF-7 (control: −17.8 days), 12.8 days for R-27 (control: −12.5 days∼14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E2 in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E2. Discrepancies between the effects of E2 on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conductingin vitro growth studies.In vitro clonogenic cell assay reproduced the antitumor activity of E2, indicating that E2 directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.
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  • 9
    ISSN: 1436-2813
    Keywords: adriamycin ; liposome ; metastatic lymph node
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adriamycin (ADM) entrapped in liposomes (Lip-ADM) was prepared and its therapeutic effects studied using the mouse leukemia cell line, P388, which metastasized to axillary lymph nodes after inoculation into the foot pads of CDF1 mice. Lip-ADM injections (7.5 mg/kg) were given into the foot pad at two-day intervals. Two series of experiments were performed; one in which Lip-ADM was administered on days 1, 3 and 5 following tumor inoculation, and the other in which it was administered on days 5 and 7. Both Lip-ADM injection regimens significantly inhibited metastases to the lymph nodes as compared with mice given injections of saline solution. Furthermore, the therapeutic effects of three Lip-ADM injections were significantly greater than the effects of free ADM. Histological examinations of lymph nodes revealed that three injections of Lip-ADM completely eliminated tumor cells, whereas viable tumor cells were still observed in the lymph nodes after treatment with free ADM. The results of this study suggest that Lip-ADM is useful for the treatment of lymph nodes metastases and that the local injection of Lip-ADM, through such means as endoscopy, would be recommended as a clinical mode of application.
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  • 10
    ISSN: 1436-2813
    Keywords: human tumor xenografts ; nude mouse ; SCID mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-three fresh tumor specimens obtained at surgery and 5 serially transferable human tumor xenografts were implanted subcutaneously into nude mice and mice with severe combined immunodeficiency (SCID) to compare the take rates of the fresh surgical specimens and the growth rates of the transferable strains. The overall take rates were 65% for the SCID mice and 60% for the nude mice, without any significant difference, although colon carcinoma seemed to have higher acceptance in the SCID mice with a take rate of 6/8. All the serially transferable strains were successfully accepted in the SCID mice, their growth rates being essentially identical to those in the nude mice. These results indicate that the SCID mouse can be used as a human tumor xenograft-mouse system as well as the nude mouse.
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