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At least 289 records · Page 16Linked to original sources
PubMed2000

[Radiotherapy and chemotherapy in the treatment of cancer of the rectum].

The North American consensus conference held in 1990 concluded that the best currently available adjuvant treatment for cancer of the rectum (T3, N1 to N3) was postoperative combination radiotherapy and chemotherapy. In 1994, the consensus conference held in Paris concluded that the benefit observed after preoperative irradiation warranted assessment of the effect of preoperative radiochemotherapy. To decide between these two consensus conclusions, it would be most logical to compare preoperative radiotherapy with postoperative radiochemotherapy in a group of patients with similar echo-endoscopic or imaging findings.

Antimetabolites, Antineoplastic↗
PubMed1976

Treatment of spontaneous leukemia in AKR mice with chemotherapy, immunotherapy, or interferon.

AKR mice are genetically destined to develop Gross (RNA) virus-induced lymphatic leukemia. Leukemic AKR mice treated with combination vincristine, cyclophosphamide (Cytoxan), and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea sustained a 180% increase of life-span. Combination chemotherapy plus immunization with neuraminidase-treated allogeneic (Gross virus-induced) G2G leukemic cells intradermally resulted in 35% of animals surviving beyond 150 days without evidence of the disease. It is significant that allogeneic E2G leukemic cells as immunogen were as effective in prolonging the life-span of the immunized leukemic AKR mice as were syngeneic leukemic thymocytes. Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), an antiviral compound, alone showed no apparent antitumor effect. However, in experiments in which the clinically diagnosed leukemic AKR mice received a combination of cytoreductive therapy [vincristine plus prednisone or, more effectively, vincristine, Cytoxan plus 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, followed by Virazole], there was a noticeable reduction of the viral titer, a delay in the reappearance of viable clonogenic cells, and an increase in the survival time for the leukemic AKR mice as compared to those receiving cytoreductive therapy alone. The effectiveness of purified mouse interferon in AKR mice was also examined. The decrease in the viral titer of animals that received interferon treatment was markedly greater than of those receiving a combination of cytoreductive therapy with Virazole or immunotherapy. The administration of mouse interferon had a direct effect on the appearance of the spontaneous leukemia in AKR mice. The median life-span of the control animals was 36 weeks, whereas 45% of the AKR mice treated with five doses of 5 X 10(4) units of interferon are still alive at 54 weeks of age. Thus, interferon not only reduces the Gross murine leukemia virus titer in the chronically infected AKR mice but also significantly delays the appearance of the primary lymphoma.

AKR murine leukemia virus↗
PubMed2000

[Current status and problem of adjuvant chemotherapy for curatively resected gastric cancer].

Randomized controlled trials (RCT) on adjuvant chemotherapy for gastric cancer published in the West and Japan were reviewed. Although several small trials showed positive data, adjuvant chemotherapy for curatively resected gastric cancer has been thought to be ineffective in western countries. Results of Japanese RCTs also have not become evidence of its benefit. Despite this, suggestive data by non-predefined subset analyses of old RCTs have been misread as definitive evidence of benefit because of less understanding of clinical statistics in Japan. As a result most Japanese patients have received postoperative adjuvant chemoimmunotherapy. Recently understanding of clinical trial has spread gradually and well designed RCTs with sufficient sample size have been reported. First of all we have to determine the efficacy of adjuvant chemotherapy by carefully designed RCT using surgery alone arm as control.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Recent advances is surgical adjuvant chemotherapy for colorectal cancer].

To evaluate the significance of surgical adjuvant chemotherapy, randomized controlled trials (RCTs) of adjuvant chemotherapy after curative resection for colorectal cancer were reviewed. Several multi-drug systemic chemotherapies (MOF, MMC/FT, 5-FU, UFT p.o.) were useful as adjuvant treatment to improve survival or disease-free survival of patients with colorectal cancer. Moreover, a worldwide meta-analysis suggested that continuous intraportal 5-FU infusion improves survival. Combination chemotherapy trials utilizing 5-FU and levamisol (LEV) demonstrated a survival advantage in patients with high risk colon cancer. Recently, many RCTs have substantiated the benefits of treatment with 5-FU/Leucovorin (LV) and this treatment is widely used as adjuvant treatment for the patients with Dukes C resected colon cancer in Europe and the U.S.A. Now, with the increasing use of oral chemotherapy drugs, new trials comparing oral UFT/LV with intravenous 5-FU/LV are being implemented to investigate these drugs in terms of QOL, toxicity and cost. Furthermore, the new drug irinotecan (CPT-11) is now under investigation to see if it brings added efficacy to 5-FU/LV. In Japan, two major groups (N-SAS-CC and TAC-CR) are comparing surgery alone and UFT alone in patients with Dukes C colon and rectal cancer. From these results, surgical adjuvant chemotherapy seems to be effective in the treatment of patients with high risk colon cancer and those with rectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1975

Inhibition and recovery of DNA synthesis in host tissues and sensitive and resistant B16 melanoma after 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, a predictor of therapeutic efficacy.

Single doses of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea caused transient suppression of [3H]thymidine incorporation into DNA in bone marrow and gastrointestinal mucosa and more prolonged inhibition of such incorporation in B16 melanoma. A single dose of 1-(2-chloroethyl) -3- (trans-4-methylcyclohexyl) -1-nitro-sourea, 16 mg/kg, doubled the mean life-span after treatment of C57BL times DBA/2F1 male mice bearing 12-day-old B16 melanomas. Subsequent doses timed to minimize toxicity and maximize antitumor effect, however, produced no further prolongation of survival, and studies with B16 melanoma previously expsed to 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea demonstrated that the suppression of [3H]thymidine incorporation into DNA was no longer prolonged beyond that seen with normal host tissues. The loss of clinical efficacy was accompanied by a loss of differential suppression of [3H]thymidine incorporation into DNA between the tumor and host tissues.

Animals↗
PubMedDate not supplied

Differential sensitivity of colony-forming cells of hemopoietic tissue, Lewis lung carcinoma, and B16 melanoma to three nitrosoureas.

A comparison has been made of the effects of three nitrosoureas (BCNU, CCNU, and methyl-CCNU) on the cells of Lewis lung carcinoma and B16 melanoma in vivo using a new in vitro method for assaying colony-forming cells. In addition, the effect on early hemopoietic precursors has been studied using the in vivo spleen colony assay and the in vitro agar colony assay. The results show that the three nitrosoureas are selective against Lewis lung carcinoma and B16 melanoma relative to normal hemopoietic precursors. Furthermore, the effect of these nitrosoureas is unchanged when the rate of proliferation of the hemopoietic precursor cells is increased.

Animals↗
PubMed1976

The inhibition of DNA synthesis by cannabinoids.

Several of the cannabinoids found in marihuana have been shown to inhibit tumor growth and increase the life-span of mice bearing the Lewis lung adenocarcinoma. When trypsin-dispersed isolated Lewis lung cells are incubated in vitro, they maintain their capacity to carry out macromolecular synthesis (RNA, DNA, protein). This process can be inhibited by cytosine arabinoside, actinomycin D, or methyl-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas cyclophosphamide, an agent that must be bioactivated, was inactive. Inhibition of DNA synthesis as measured by [3H]thymidine uptake into acid-insoluble material was used as an index of cannabinoid activity against isolated Lewis lung cells, L1210 leukemia cells, and bone marrow cells incubated in vitro delta9-, delta8-, 1-hydroxy-3-n pentyl-, and 1-delta8-tetrahydrocannabinol, and cannabinol demonstrated a dose-dependent inhibition of DNA synthesis whereas cannabidiol and 1-hydroxy-3-n-pentylcannabidiol were markedly less inhibitory in our in vitro cell systems. Furthermore, our in vitro observations with these cannabinoids are supported by in vivo tumor inhibition studies. Ring modifications as in cannabichromene or cannabicyclol abolish in vitro activity as does dihydroxylation at the 8beta and 11 positions of 1-delta9-trans-tetrahydrocannabinol. Delta9-trans-tetrahydrocannabinol demonstrated the least toxicity of all inhibitory cannabinoids in vivo; this is supported by its lesser effect on bone marrow DNA synthesis in vitro.

Animals↗
PubMed2002

[The introduction of preoperative staging laparoscopy and molecular diagnosis of peritoneal lavages for the treatment of advanced gastric cancer].

In this study, intra-peritoneal chemotherapy was performed for advanced gastric cancer with serosal invasion. We assessed the efficacy of the chemotherapy using quantitative genetic diagnosis with peritoneal lavages collected before and after chemotherapy at staging laparoscopy and/or gastrectomy. Cases in which genetic diagnosis of peritoneal lavages showed negative results, or changed from positive to negative after chemotherapy, had a good prognosis. On the other hand, cases in which genetic diagnosis showed positive results after chemotherapy had worse prognosis. Intra-peritoneal chemotherapy may be indicated for patients with a positive genetic diagnosis only and cases becoming negative as a result of this therapy may have a better prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1976

A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.

The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.

Amphotericin B↗
PubMed1976

Growth support of small B16 melanoma implants with nitrosourea-sterilized fractions of the same tumor.

B16 melanoma cells sterilized in vitro with 1,3-bis(2-chloroethyl)-1-nitrosourea or in vivo with trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, have been used to enhance the percentage of tumor takes with small s.c. implants of viable cells and to reduce the latent period between tumor implantation and palpability. The admixture of trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea-inactivated cells with viable cell implants reduced the number of cells required to produce tumors in 50% of the animals by approximately 3 log10 units and markedly reduced the time of tumor appearance from implants of up to 10(6) cells. Similar results were obtained with 1,3-bis(2-chloroethyl)-1-nitrosourea-sterilized cells. The growth-supporting effect obtained with the nitrosourea-inactivated cells appeared to be as pronounced as that previously reported, for this tumor system, with radiation-inactivated cells.

Animals↗