Significant Increase In Survival Time Research Articles

Various uses of BCG and allogeneic acute leukemia cells to treat patients with acute myelogenous leukemia

Ninety-six remission patients with acute myelogenous leukemia have been treated with various forms of immunotherapy and chemotherapy in three distinct studies and the clinical outcome of these patients has been reported. In the first study 22 patients were maintained on chemotherapy alone and 28 patients were given the same chemotherapy and additional immunotherapy consisting of BCG and irradiated allogeneic AML cells given at separate sites weekly. It was found that there was a significant increase in survival time of the patients who received immunotherapy (median 510 days) compared with the chemotherapy alone patients (270 days). The p value for this was 0.03. The reason for this prolongation of survival was mainly due to a markedly increased survival time of immunotherapy patients after they relapsed when compared with the chemotherapy patients (165 days compared with 75 days median, p equal to 0.0005). In the second sequential study 24 patients were given immunotherapy alone consisting of irradiated allogeneic AML cells and BCG given at separate sites, and this was compared with unirradiated allogeneic cells and BCG given to 22 patients. There was no difference in the remission length or survival between these two groups. In the third study 13 patients received irradiated cells and BCG as in Study 1 and a further 11 patients received the same immunotherapy but also received a mixture of cells and BCG given during the first three months. There was no difference in the remission and survival of these two groups. The significance of these results is discussed.

Carcinostatic activity of 4-hydroxy-2-pent-en-1-al against transplantable murine tumour lines

The carcinostatic activity of 4-hydroxy- 2-pent-en- 1-al (HPE) was studied with the following transplantable murine tumours in the ascitic form: Ehrlich carcinoma, Gardner lymphosarcoma, and Sarcoma 180. A bioassay system was used involving treatment of tumour cell suspension in vitro with 0·04–1·28 mM HPE for 60 min at 37°C and re-injection of treated cells into groups of mice. Significant increases in survival time were observed with concentrations of HPE greater than 0·16 mM ( 16·8%–91·5%) and “indefinite survivors” (surviving beyond day 60 following transplantation) were obtained using HPE ( 0·64–1·28 mM) in all three tumour lines. The ID 50 ( 0·095–0·153 mM) and ID 90 ( 0·131–0·315 mM) values obtained demonstrate that HPE is a relatively potent carcinostatic agent in vitro in the tumour lines tested in this study. Results obtained with HPE under conditions in vitro do not distinguish between a direct cytotoxic effect of HPE on the ascitic tumour cells or a possible extension in the generation time of these cells. Treatment of these ascitic cell lines in vivo with multiple i.p. injections of HPE ( 4–128 mg/kg body wt/day) on days 3 and 4 following transplantation resulted in no significant increase in survival time compared to controls for both Ehrlich and Gardner. Sarcoma 180 responded with a moderate inhibition of tumour growth of 24% and 35% at 64 and 128 mg/kg/day of HPE.

The effect of treatment with L-phenylalanine mustard and L-phenylalanine mustard antibody on the survival time of mice with intracerebral ependymoblastomas.

AbstractPrevious work has shown a decreased rate of growth of mouse ependymoblastomas treated with an antigen which fixes to the cell wall, followed by an antibody to the tumor cell marker. The present study was designed to compare the survival time of mice with intracerebrally implanted ependymoblastomas that were treated with the above method with the survival time of controls. Eight groups of C3 H male mice were subjected to intracerebral implantation of ependymoblastoma. Five days following implantation, each group was subdivided into four subgroups, and the subgroups were treated with intravenous normal saline, intravenous antibody, intracarotid L–phenylalanine mustard and intracarotid L–phenylalanine mustard followed by intravenous antibody, respectively. The treated mice showed statistically significant increase of survival time, as compared with the controls. It is possible that by changing some of the treatment parameters, more long‐term results can be achieved.

Target-organ treatment of neurotropic virus disease with interferon inducers.

Interferon inducers were used against vaccinial encephalitis to study the target-organ treatment of neurotropic disease and to correlate interferon levels and the antiviral state following such treatment. A 45-mug amount of statolon, 30 mug of polyribinosinic-polyribocytidylic acid complex (poly I.poly C), or 0.0154 HA unit of Sendai virus given intracerebrally protected 100% of mice challenged the next day with 1,000 median lethal doses (LD(50)) of vaccinia virus. Significant protection against 1,000 LD(50) of vaccinia virus persisted for 1, 4, or 3 weeks after poly I.poly C, statolon, or Sendai virus (154 HA units), respectively. These doses of poly I.poly C and statolon were also used to study postinfection treatment. Mice challenged with 1, 10, 100, or 1,000 LD(50) were treated intracerebrally with poly I.poly C or statolon 24 or 48 hr later. Significant increases in survival time were seen in mice challenged with 1 to 100 LD(50) of vaccinia virus and treated 24 hr later. At challenges of 10 or 100 LD(50), statolon was more effective than poly I.poly C in increasing survival times. When treatment was delayed until 48 hr after infection, significant increases in survival time occurred only when the challenges were in the range of 1 to 10 LD(50), with poly I.poly C and statolon being equally effective. Interferon was measured by Finter's dye-uptake method, with L-929 cells and Semliki Forest virus. Poly I.poly C, statolon, or Sendai virus, given intracerebrally to mice, produced serum interferon peaks of 5,120 units/ml at 2 hr, 2,560 units/ml at 12 hr, or 320 units/ml at 18 hr, respectively. Corresponding brain interferon peaks were 640 units/g at 2 hr, 640 units/g at 4 to 24 hr, and 960 units/g at 72 hr.

Meso-Inositol Hexanicotinate Induced Protection against Experimental Anoxia and Oedema

It is shown that Meso-Inositol Hexanicotinate (MIHN; Hexopal) inhibits experimentally induced oedema of the paw in rats and that mice exposed to hypoxic atmospheres (4% oxygen) show significant increase in survival time if pre-dosed with MIHN. The protection against oedema and hypoxia conferred by MIHN in experimental animals may well be related to the mode of action of the substance in man, and particularly could explain the usefulness of MIHN in the treatment of cerebral and peripheral atherosclerosis.

Effect of reticuloendothelial system stimulation on resistance to Rous sarcoma virus infection in chicks.

AbstractBy using a non‐toxic reticuloendothelial system stimulant, lipid‐Restim, derived from shark livers, we were able to demonstrate the following effects on growing Rous sarcoma tumors in young chicks. Prechallenge Restim treatment: Significant reduction of the percentage of chicks with tumors and prolongation of the latent period resulted from combined administration of Restim and specific antiserum. Postchallenge Restim treatment: The mortality data indicated that there was a significant increase in survival time and survival rate. Complete regressionsThe term “regression” is used in this paper to mean complete macroscopical disappearance of the primary tumor at the site of inoculation of the virus. occurred in a significant number of the Restim‐treated chicks compared to the controls. Possible explanations of these findings are discussed.

Evaluation of chemical agents against the plasma cell tumor LPC-1 in mice

Utilizing the advanced stage of an ascitic plasma cell tumor LPC-1 in mice, thirty-one drugs, plus cyclophosphamide employed as a positive standard, were tested for their ability to prolong the survival time of the animals. A determination was also made of the effect of the drugs on the biochemical parameter, abnormal protein production. Four drugs had an effect on both of these indices, i.e. tryptophan mustard (NSC-62403), aniline mustard (NSC-18429), cyclophosphamide (NSC-26271) and 5-fluorouracil (NSC-19893). Two of these, tryptophan mustard and cyclophosphamide, have been shown to be active clinically against plasma cell tumors. Nine additional compounds caused a significant increase in survival time but did not cause the abnormal protein to disappear. The current study indicates that the LPC-1 tumor offers a suitable test system for screening compounds for clinical trial against myeloma. A comparison is also made of the relative activities of the compounds in the L1210 leukemia, Walker 256 carcinosarcoma (IM) and LPC-1 systems in relation to clinical experience.

Effect of age, sex, gonadectomy, sodium chloride intake, and treatment with cortisol acetate upon the lifespan of adrenalectomized mice of an albino strain.

SUMMARY The effects of age, sex, gonadectomy, administration of NaCl and treatment with cortisol acetate (CA) upon survival after adrenalectomy was investigated in mice of an albino strain. Complete bilateral adrenalectomy was followed by death in all mice except in the group maintained by administration of CA. A period of maintenance with CA was assumed to allow accessory cortical tissue to grow to an extent that, in some mice, it could maintain life when the replacement therapy was withdrawn. The incidence of indefinite survival was greater in mice treated with 50 and 75 μg CA than in those injected with 12·5 and 25 μg daily. Evidence is presented which suggested that operative shock did not contribute significantly to deaths occurring later than 36 hr after adrenalectomy. The lifespan of adrenalectomized mice increased with age at operation, but was not affected by the addition of NaCl to the drinking water. In female mice adrenalectomized prior to puberty the ovaries appeared to promote a slight but significant increase in survival time. This effect was not observed in mice adrenalectomized at 6 or 12 weeks of age. Castration did not affect the lifespan of immature male adrenalectomized mice. The majority of a group of male mice adrenalectomized at 21 days of age were able to survive, and grow in body weight at about half the rate of control-operated mice, as long as treatment with CA in daily doses ranging from 12·5 to 75 μg was continued. The average lifespan appeared to be greater and the number of mice dying during treatment less at higher levels of CA treatment, but these differences were not significant. A loss of body weight occurred in all CA-treated adrenalectomized mice during the terminal stages of adrenal insufficiency. Mice which survived indefinitely gained in body weight during the injection period at a rate similar to that of control-operated mice.

Influence of ascorbic acid and chlorpromazine on body temperature and resistance of mice to drowning.

SummaryBuffered ascorbic acid and chlorpromazine were injected intraperitoneally into mice and the effect on body temperature and anoxic resistance to drowning measured. Significant increases in survival time were noted with ascorbic acid and especially with chlorpromazine. Lowered body temperatures were noted with both compounds. When anoxic survival to drowning was measured, prolongation of life was increased to a maximum of 40% with ascorbic acid and 121% with chlorpromazine.

THE EFFECT OF NORADRENALINE ON THE SURVIVAL OF RATS SUBJECTED TO HEMORRHAGIC SHOCK

Reports of the efficacy of l-noradrenaline in the treatment of clinical shock stimulated an investigation of its effect in controlled hemorrhagic hypotension. Seventy-three 350-g. male Sprague–Dawley rats were subjected to a standardized hemorrhagic shock procedure. Of 15 control animals that received no treatment, only one survived for 48 hours; none survived of the five controls that received a constant intravenous infusion, after the shock procedure, of 5% glucose in distilled water until death or for 36 hours. The treated animals received, after the shock procedure, an infusion of l-noradrenaline (0.5–2.0 μg./min.) in 5% glucose in distilled water. The survival rates for the treated animals were: treatment for 1 hour, 1/8; treatment for 4 hours, 4/15; treatment until death or for 36 hours, 8/15. Fifteen animals received, in addition to noradrenaline for 36 hours, hydrocortisone administered intravenously (0.7 μg./min.) or intramuscularly (2.5 mg. every 6 hours); seven of these animals survived.Analysis of variance showed that there was no difference in the shock procedure undergone by the controls and by the treated survivors. The Chi square test on the survival rates revealed that the infusion of noradrenaline for 1 hour or 4 hours did not improve survival, but infusion for 36 hours produced a very significant increase in survival time and in total survival rate. The addition of hydrocortisone neither enhanced nor impaired this improvement.

THE EFFECT OF NORADRENALINE ON THE SURVIVAL OF RATS SUBJECTED TO HEMORRHAGIC SHOCK

Reports of the efficacy of l-noradrenaline in the treatment of clinical shock stimulated an investigation of its effect in controlled hemorrhagic hypotension. Seventy-three 350-g. male Sprague–Dawley rats were subjected to a standardized hemorrhagic shock procedure. Of 15 control animals that received no treatment, only one survived for 48 hours; none survived of the five controls that received a constant intravenous infusion, after the shock procedure, of 5% glucose in distilled water until death or for 36 hours. The treated animals received, after the shock procedure, an infusion of l-noradrenaline (0.5–2.0 μg./min.) in 5% glucose in distilled water. The survival rates for the treated animals were: treatment for 1 hour, 1/8; treatment for 4 hours, 4/15; treatment until death or for 36 hours, 8/15. Fifteen animals received, in addition to noradrenaline for 36 hours, hydrocortisone administered intravenously (0.7 μg./min.) or intramuscularly (2.5 mg. every 6 hours); seven of these animals survived.Analysis of variance showed that there was no difference in the shock procedure undergone by the controls and by the treated survivors. The Chi square test on the survival rates revealed that the infusion of noradrenaline for 1 hour or 4 hours did not improve survival, but infusion for 36 hours produced a very significant increase in survival time and in total survival rate. The addition of hydrocortisone neither enhanced nor impaired this improvement.

Effect of Sanguinin, an antibacterial agent from blood, on streptococcal infection in mice.

Summary and ConclusionsThe blood hydrolysate Sanguinin was tested in vivo in 268 albino mice accompanied by 221 untreated controls for its effectiveness against the beta-hemolytic Streptococcus zooepidemicus. Sanguinin solution (20 mg/ml) was inoculated subcutaneously (0.25 to 1.0 mg/mouse daily, usually for 4-6 days) either prior or after infection. Suppressive effect on the course of the infection was noted in all series of treated mice. A significant increase in survival time was noted in the pretreated series with an average survival percentage of 38.9 compared with 6.0 of the total of untreated controls. It does not appear that a direct correlation can be established between the survival rates and the intake of Sanguinin or the length of its administration, however, pretreatment seems to be of decisive value.