A retrospective study on radiotherapy and radiochemotherapy in esophageal cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
W S Hong
Publications and source records attributed to W S Hong.
In vitro antitumor effect of recombinant human tumor necrotizing factor on cultured human cancer cell lines and freshly isolated lung cancer cells by the human tumor clonogenic assay.
In vitro antitumor effects of human recombinant tumor necrotizing factor (rH-TNF) were examined against nine lung cancer cell lines including six non small and three small cell lung cancer, four stomach cancer cell lines and 30 freshly isolated lung cancer cell samples by the human tumor clonogenic assay. rH-TNF did not show any inhibitory effect on the colony formations of lung and stomach cancer cell lines, except for PC10 established from squamous cell carcinoma even at the high concentration. The overall response rate of fresh material was 11.5%. The colony formations of only two materials from 20 patients without prior chemotherapy were significantly suppressed by rH-TNF in vitro. Three specimens of adenocarcinoma exhibited more than 70% decrease in colony number by treating with 100 and 1000 u/ml of rH-TNF resulting in the response rate of 15.8% (3/19). From these results, it can be concluded that rH-TNF has modest direct cytotoxic effect on lung cancer, and additional study against adenocarcinoma of the lung might be warranted.
Antineoplastic Agents↗
The colony inhibition of a new chemotherapeutic agent (KW2152) against human lung cancer cell lines.
The human tumor colony assay was used to evaluate the effect of a new chemotherapeutic agent (KW2152) on colony inhibition of four non-small cell lung cancer cell lines and a mouse cell line. With continuous exposure experiments, KW2152 induced greater than or equal to 70% colony inhibition of PC-7 (human adenocarcinoma), PC-10 (human squamous cell) and PC-13 (human large cell) at a drug concentration of 10 mcg/ml. In one hour exposure experiments, KW2152 caused a significant reduction in colony formation (less than or equal to 30% of control) only at the highest concentration tested (100 mcg/ml). KW2152 showed significant in vitro activity against human non-small cell lung cancer cell lines. Due to these promising results, it was suggested that KW2152 should be evaluated in clinical trials.
Antineoplastic Agents↗
In vitro colony inhibition of carboplatin against stomach and lung cancer cell lines in comparison with cisplatin.
The effects of carboplatin and cisplatin on colony formation in stomach and lung cancer cell lines were examined and compared. The colony-inhibitory activity of carboplatin against stomach and lung cancer cell lines was similar to that of cisplatin when one-tenth of the peak plasma concentration of each drug was used (r = 0.80). One of the four stomach cancer cell lines was sensitive to carboplatin although all the stomach cancer cell lines were resistant to cisplatin. Of the three small cell lung cancer cell lines tested, two were sensitive to both carboplatin and cisplatin, and only one cell line (N857) was resistant to cisplatin; all the non-small cell cancer cell lines tested were resistant to both drugs. On the basis of these preliminary results, we suggest that carboplatin has potential therapeutic activity against stomach cancer and should be evaluated carefully from this aspect.
Carboplatin↗
Colony inhibitory effect of recombinant human tumor necrosis factor (rH-TNF) and/or recombinant human interferon (rH-IFN)-alpha, -beta and -gamma on human lung cancer cell lines.
This study was conducted to assess, by continuous exposure, the inhibitory effects of rH-TNF and rH-IFN-alpha, -beta and -gamma, either alone or in combination, on the colony formations of human lung cancer cell lines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), PC-10 (squamous cell carcinoma) and PC-13 (large cell carcinoma). Additional experiments were performed with L929 (transformed murine fibroblast), because of its known high sensitivity to TNF. rH-TNF inhibited the colony formations of PC-10 and L929 even at a low concentration (10 U/ml). However, PC-7, PC-9 and PC-13 were resistant to rH-TNF. rH-IFN-alpha, -beta and -gamma inhibited the colony formation of PC-10 (less than 50% of control) at the highest concentration tested (10(4) U/ml), but only rH-IFN-beta inhibited that of PC-7. PC-9, PC-13 and L929 were insensitive to all three rH-IFNs, even at the highest concentrations tested. Combination effects of rH-TNF and rH-IFN-alpha or -gamma were synergistic only at the highest concentration combinations tested in PC-9. However, the maximum inhibition of colony formation of PC-7, PC-9 or PC-13 in any concentration combination treatment was less than 50%.
Antineoplastic Combined Chemotherapy Protocols↗
In vitro growth inhibition of cisplatin-resistant human lung cancer cell lines by recombinant human tumor necrosis factor and/or recombinant human interferon-gamma by virtue of collateral sensitivity.
The colony-inhibitory effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-gamma (rH-IFN-gamma) were evaluated in four human lung cancer cell lines and their cisplatin-resistant sublines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), H69 and N231 (small cell lung cancer) and four cisplatin-resistant sublines, PC-7/1.0, PC-9/0.5, H69/0.2 and N231/0.2, which were 20.0, 7.1, 4.8 and 8.4 fold resistant to cisplatin, respectively, compared to the respective parental cell line in terms of IC50 in a soft agar colony assay. All parental cell lines were resistant to rH-TNF and rH-IFN-gamma, alone or in combination. However, two resistant sublines showed sensitivity to rH-TNF and rH-IFN-gamma. Colony formation by PC-9/0.5 was significantly inhibited, in the absence or presence of cisplatin, by 10(2) U/ml of rH-TNF (less than 50% of control) and the inhibition was synergistic with that produced by 10(3) or 10(4) U/ml of rH-IFN-gamma. RH-IFN-gamma inhibited the colony formation of H69/0.2 only at the highest concentration tested (10(4) U/ml) (less than 50% of control) and the combined effect with rH-TNF was additive. These results suggest that rH-TNF and rH-IFN-gamma may have some potential in overcoming cisplatin resistance by virtue of collateral sensitivity.
Cisplatin↗
[In vitro drug sensitivity test].
Human tumor clonogenic assay(HTCA) not only offers potential advantages for prediction of the sensitivity of individual patients, to anticancer drugs, but also for the development and preclinical testing of prospective new antineoplastic agents. However, HTCA has several theoretical and technical problems, such as a low success rate, the requirement of large numbers of tumor cells and the long time period necessary for evaluation. In order to solve these problems, the MINI-hybrid assay has been developed. We reviewed our experiences to date with chemosensitivity testing by MINI-hybrid assay. Twenty-two of 23 tumors gave evaluable chemosensitivity results (95.6%), and the range of thymidine incorporation for evaluable assays was 7 X 10(2)-1.2 X 10(5)cpm. In addition, the results of drug sensitivity testing of cultured cell lines by MINI-hybrid assay were well correlated with those obtained by HTCA. With its high evaluability rates, the need for fewer cells, the short duration (5 days) required and ease of quantitation, the MINI-hybrid assay is widely applicable to the chemosensitivity testing of human tumors.
Antineoplastic Agents↗
[Nursing care of the patient with acute bleeding--panel discussion].
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Critical Care↗
Use of methylcellulose in small bowel follow-through examination: comparison with conventional series in normal subjects.
BACKGROUND: To evaluate and optimize a modified small bowel follow-through examination (SBFT) by using an oral administration of a large amount (600 mL) of methylcellulose after taking a small amount of barium. METHODS: Ninety-nine normal subjects underwent modified SBFT with an oral administration of 600 mL of 0.5% methylcellulose after taking 100 mL of 120% or 100, 150, or 200 mL of 70% w/v barium. The transradiancy and distensibility of the bowel and the transit time were compared with those of 39 other normal subjects who underwent conventional SBFT with 500 mL of 70% w/v barium. RESULTS: Except for two subjects who developed diarrhea immediately after examination, no patients complained of acute symptoms, such as abdominal pain or vomiting. Modified SBFT was much superior to conventional series for obtaining good bowel transradiancy and rapid transit time (range = 37-49 min), but bowel distention was not significantly improved. The use of 150 mL of 70% w/v barium was better than the other three modified techniques for achieving good bowel transradiancy, rapid transit time, and less occurrence of flocculation. CONCLUSION: Modified SBFT is a simple method for easily improving the image quality in terms of bowel transradiancy and transit time.
Administration, Oral↗
Intestinal tuberculosis with abdominal complications: radiologic and pathologic features.
BACKGROUND: To investigate radiologic and pathological features of intestinal tuberculosis with abdominal complications. METHODS: Twenty-two patients with 23 surgically proven complications (nine intestinal obstructions, eight perforations, three fistulae, and three intestinal bleeds) were analyzed. Medical records, radiologic studies, and pathologic examinations were reviewed with special emphasis on searching for the common features in each group of complication. RESULTS: The most important single feature in seven of the nine patients with intestinal obstruction was the presence of stricture. In the remaining two patients, bowel adhesion was a primary cause of obstruction. In eight patients with intestinal perforation, both obstruction and ulcerations in the dilated proximal loop were the important features in six, and multiple deep ulcerations without obstruction was a primary cause in the remaining two. The common features in three patients with fistulae were focal or multiple strictures, severe adhesions, and fibrotic bowel wall. Intestinal bleeding originated from diffuse mucosal ulcerations. The abdominal complications occurred during antituberculous therapy in 10 of the 22 patients. CONCLUSION: Understanding the radiologic and pathologic features of intestinal tuberculosis with complications help in making an appropriate clinical decision for the treatment strategy. Close observation is necessary, especially in those patients who are acutely ill during antituberculous medical therapy. Enteritis-Intestines, diseases-Intestines, infection-Intestines, perforation-Intestines, stenosis or obstruction.
Female↗
In vitro antitumor activity of a new platinum complex, cis-malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum (II) (SKI 2053R), against human lung and stomach cancer cell lines.
The in vitro antitumor activity of a new platinum complex, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP) and carboplatin (CBDCA) was determined against two human lung cancer (PC-9 and PC-14) and two human stomach cancer (MKN-45 and KATO III) cell lines by human tumor clonogenic assay. The activity of SKI 2053R was compared with those of CDDP and CBDCA in terms of relative antitumor activity (RAA, peak plasma concentration/IC50). Mean IC50 values (microgram/ml) of SKI 2053R, CDDP and CBDCA were 6.4 +/- 0.8, 1.8 +/- 0.7 and 20.6 +/- 12.2, respectively. The RAAs of SKI 2053R, CDDP and CBDCA were 1.6 +/- 0.4, 2.0 +/- 0.8 and 1.2 +/- 0.6, respectively. The differences in these values were not statistically significant. The results, demonstrating that antitumor activity of SKI 2053R is similar to those of CDDP and CBDCA, suggest that SKI 2053R is an interesting candidate for further development as a new anticancer drug.
Adenocarcinoma↗
Alterations of p53 gene in primary gastric cancer tissues.
This study was conducted to investigate the p53 gene alterations in 25 surgically-resected gastric adenocarcinomas in the Korea Cancer Center Hospital by polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) for exons 4-8 and immunohistochemical staining (IHCS) with anti-p53 antibody, DO-7. p53 mutations were detected in nine (36%) out of 25 cancer tissues by PCR-SSCP in exon 4-8: 0,1,1,6 and 1 mutations in exons 4,5,6,7 and 8, respectively. All tissues were also tested by IHCS, and positive staining was observed in 11 cases (44%). A discrepancy of the results between the two methods was observed in four cases. In one which showed positivity by PCR-SSCP a negative reaction by IHCS, the two base deletion was observed in exon 7. On the other hand, in three cases the mutation was detected only in IHCS but not in PCR-SSCP. The exact mechanism by which this discrepancy develops is not clear at present, although it may be due to the mutation of other exons not tested in this study or the relatively low sensitivity of the PCR-SSCP method. The incidence of p53 gene mutations was analysed according to pathologic stage and histological differentiation, but no significant difference was observed between the p53 alterations and these factors. By combined use of PCR-SSCP and IHCS, 48% of the 25 primary gastric cancer were considered to have mutations of the p53 gene. These results suggest that p53 mutation is not an infrequent event in primary gastric cancer and the p53 gene plays an important role in the carcinogenesis process of gastric cancer.
Adult↗
In vitro cytotoxicity, pharmacokinetics and ex vivo pharmacodynamics of a new platinum compound, cis-malonato [(4R,5R-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclopentane] platinum (II).
The in vitro cytotoxicity of a new platinum complex, cis-malonato [(4R, 5R)-4,5-bis(aminomethyl)-1,3-dioxolane 2- spiro 1' cyclo-pentane]platinum(II) (SKI 2054R) and cisplatin (CDDP) was evaluated against two human stomach adenocarcinoma cell lines (MKN-45 and KATO III) and a human lung adenocarcinoma cell line (PC-14). The in vitro 50% inhibitory concentration (IC50) values of SKI 2054R and CDDP against MKN-45, KATO III, and PC-14 were 1.21 and 0.51, 2.11 and 0.83, and 2.90 and 0.77 micrograms/ml, respectively. The pharma-cokinetic and ex vivo pharmacodynamic studies on SKI 2054R and CDDP were performed in beagle dogs. Equitoxic doses of SKI 2054R and CDDP (7.0 and 3.0 mg/kg, respectively) were administered i.v. bolus to beagle dose in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the two drugs declined in a biexponential fashion. The mean area under the concentration-tine curve (AUC(0)--> infinity) determined for ultrafiltrable platinum derived from SKI 2054R, as an active component was 6.61 +/- 2.34 micrograms . h/ml (mean +/- S.D.), with an initial half-life of 0.26 +/- 0.14 h, a terminal half-life of 1.57 +/- 0.71 hour, a total clearance of 17.65 +/- 4.99 ml/min/kg, and a steady-state volume of distribution of 1.46 +/- 0.11 l/kg. The ex vivo antitumor activity of SKI 2054R was assessed using the ultrafiltrable plasma against MKN-45, KATO III, and PC-14 by tetrazolium-dye (MTT) assay and was compared with that of CDDP using the antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value recorded for SKI 2054R was higher than that noted for CDDP; however, statistical difference was not observed between SKI 2054R and CDDP, suggesting that the antitumor activity of SKI 2054R is comparable to that of CDDP. These results suggest that SKI 2054R is a new platinum complex which is worth being evaluated further.
Adenocarcinoma↗
Elevation of serum type IV collagen in liver cancer as well as liver cirrhosis.
Studies on the level of serum type IV collagen (IV C) have usually been focused on the disease with diffuse hepatic fibrosis. To investigate whether serum level of IV C was predictive for the development of liver cancer as well as liver cirrhosis, serum IV C level was measured by a one-step sandwich enzyme immunoassay. The mean level of serum IV C was 73.3 +/- 31.3 ng/ml in 48 controls. The levels (ng/ml) of IV C were 396.4 +/- 254.9, 429.6 +/- 320.7, 420.6 +/- 322.8, and 362.9 +/- 247.4 respectively in 11 patients with chronic hepatitis, 11 with liver cirrhosis, 16 with hepatocellular carcinoma (HCC) with cirrhosis, 10 with HCC without cirrhosis, and 10 with metasatic liver cancer, which were significantly higher than that in controls (p < 0.05). Serum IV C levels were also evaluated using a cut-off value which was determined as the mean plus two standard deviations in the controls, 136 ng/ml. The elevations above the cut-off value were observed in 91, 100, 80, and 90% respectively of 11 patients with cirrhosis, 16 with HCC with cirrhosis, 10 with HCC without cirrhosis, and 10 with metastatic liver cancer, while only one (9%) of 11 chronic hepatitis patients and none (0%) of 48 controls had elevated levels. The levels of serum IV C were analysed with regard to age, sex, serum levels of albumin, globulin, transaminases, alpha-fetoprotein, and diameter of liver mass, a significant difference being observed only between the diameter of HCC and serum level of IV C (p < 0.01). These results indicate that the measurement of serum IV C is a useful for the determination of primary and metastatic liver cancer as well as liver cirrhosis.
Adult↗
Pharmacokinetics of a new platinum compound, cis-(glycolato-O,O) [(4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclohexane]plat inum (II) in dogs.
A pharmacokinetic study on cis-(glycolato-O,O)/ (4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'- cyclohexane]platinum(II) (SKI 2032R) was performed in dogs. A single dose of 2.0 mg/kg of SKI 2032R was administered i.v. bolus to three beagle dogs. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for SKI 2032R declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0 --> infinity) determined for ultrafiltrable platinum derived from SKI 2032R, as an active component, was 2.36 +/- 0.23 micrograms. h/ml (mean +/- S.D.), with an initial half-life of 0.23 +/- 0.20 hour, a terminal half-life of 1.32 +/- 0.49 hour, a total clearance of 14.17 +/- 1.50 ml/min/kg, and a steady-state volume of distribution of 1.21 +/- 0.24 l/kg.
Animals↗
Biochemical characterization of cisplatin-resistance in MKN-45 human stomach adenocarcinoma cell line.
We have established a cisplatin resistant subline, MKN/CDDP, from the MKN-45 human stomach adenocarcinoma cell line. MKN/CDDP was 10.7 fold more resistant to cisplatin, 5.4 fold resistant to carboplatin, 2.7 fold resistant to 5-fluorouracil and only 1.4 fold resistant to adriamycin. To investigate the mechanism of the cisplatin resistance in the MKN/CDDP subline, we performed the biochemical characterization of MKN-45 and MKN/CDDP. MKN/CDDP cells showed no induction in p-glycoprotein and topoisomerase II. The level of glutathione S-transferase-pi was higher in MKN/CDDP than the parent line, but a similar level of glutathione S-transferase-L isoform was observed. Superoxide dismutase activity was 1.67 fold higher in the MKN/CDDP subline than the parent line, but 60 kDa catalase was much lower in the MKN/CDDP subline. In addition to those changes. MKN/CDDP was not able to attach to the culture dish, which is probably due to the lack of fibronectin association on the cell surface. The MKN/CDDP subline revealed a variety of biochemical changes which are related to drug inactivation and to cell substratum adhesion. The significance of each modification in the development of the cisplatin resistance will be evaluated in future studies.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng.
In the present study an acidic polysaccharide ginsan, with a molecular weight of 150,000, devoid of lectin properties, was purified from Panax ginseng C.A. Meyer (Araliaceae). Ginsan induced the proliferation of T cells and B cells. Spleen cells became cytotoxic to a wide range of tumor cells without major histocompatibility complex-restriction after 4 or 5 days culture in vitro with ginsan. For the generation of these ginsan-activated killer (AK) cells adherent macrophages and CD4+ cells were needed as accessory cells. The generation of ginsan-AK cells was blocked in the presence of anti-IL-2, anti-IFN gamma, anti-IL-1 or anti-TNF alpha antibodies, showing the importance of these cytokines in the process. The surface phenotypes of the 4 day-cultured ginsan-AK cells was Thy1+, AsGM1+, CD8+, which is distinct from rIL-2 induced lymphokine activated killer (LAK) cells that were CD8. The ginsan also activated macrophages to produce reactive nitrogen intermediates and become tumoricidal. It also exhibited significant in vivo antitumor activity against B16 melanoma cells lines, and in the benzo(a)pyrene-induced autochthonous lung tumor model, at much lower doses than the maximum tolerate doses. Indeed, no mice died, which injected with ginsan at 1g/kg body weight intraperitoneally. In conclusion, 'ginsan' could potentially be an ideal nontoxic antineoplastic immunostimulator by activating multiple effector arms of the immune system.
Adjuvants, Immunologic↗
Antitumor activity of DA-125, a novel anthracycline, in human gastric and pulmonary adenocarcinoma cells resistant to adriamycin and cisplatin.
The study was undertaken to investigate the antitumor activity of DA-125, a promising new analogue of adriamycin (ADM) containing fluorine, against human gastric and pulmonary adenocarcinoma cell lines and their sublines resistant to ADM and cisplatin (CDDP) by MTT assay. The cells used were MKN-45, human gastric adenocarcinoma, PC-14, human pulmonary adenocarcinoma, and their sublines resistant to ADM, MKN/ADM and PC/ADM, and CDDP, MKN/DDP and PC/DDP. MKN/ADM and PC/ADM were 12.6- and 13.9-fold resistant to ADM, respectively, compared to the respective parental cell lines in terms of IC50. The survival was less in cells treated with DA-125 than that treated with ADM in all lines tested. The antitumor activity of DA-125 was compared with that of ADM using IC50 values and relative resistance (RR). RR was defined as the ratio of the IC50 value of the resistant subline to that of the parent line. In all lines tested, the mean IC50 values for both DA-125 and ADM were lowest in the parent cells, followed by CDDP-resistant cells and ADM-resistant cells. The IC50 values for DA-125 were lower than those for ADM in all six lines tested, although statistical significance was observed in four lines. ADM-resistant sublines were highly resistant to DA-125 (RRs for ADM and DA-125; 12.6 and 7.6 MKN/ADM and 13.9 and 10.3 in PC/ADM, respectively). On the other hand, CDDP-resistant sublines were also resistant to ADM and DA-125 when compared with the respective parent cell lines (RRs for ADM and DA-125; 2.3 and 2.0 in MKN/DDP and 4.8 and 6.0 in PC/DDP, respectively). Although DA-125 showed cross-resistance to ADM and CDDP, we recommended DA-125 to be a good candidate for further development because DA-125 exhibited remarkable antitumor activity against the parent cell lines.
Adenocarcinoma↗