Substances from marine organisms influencing tumor growth and immune responses.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Ghaffar.
Explore the source record for details and available documents.
Extracts of a marine tunicate, Ecteinascidia turbinata (Ete) were previously shown to be capable of suppressing humoral and cellular immune responses in vivo and in vitro. In the present work we have examined the mechanisms of suppression in Ete-treated DBA/2 and BALB/c mice. Treatment with Ete resulted in a significant splenomegaly accompanied by a diminished response to mitogenic stimulation, reaching coincident maxima of effect at days 4 to 6. Spleen size and blastogenic reaction returned to normal at 12 to 21 days. Cells from enlarged spleens inhibited blastogenic responses of normal splenocytes to Con A. Marker studies indicated that the suppressor activity was exerted by cells possessing T lymphocyte characteristics.
Explore the source record for details and available documents.
Corynebacterium parvum injected i.p. 1--16 days prior to i.p. antigen inoculation virtually abolished both IgM and IgG primary responses to 1 X 10(8) SRBC. The suppression was significantly marked at antigen doses ranging from 1 X 10(6)--1 X 10(9) SRBC but not at 5 X 10(9) SRBC. As little as 56 microgram C. parvum caused a marked suppression of the response to 1 X 10(8) SRBC. In secondary responses C. parvum given either one day before priming with 1 X 10(8) SRBC or one day before secondary challenge caused a dramatic suppression of both IgM and IgG PFC responses. In contrast with i.p. injected C. parvum, i.v. injection of the vaccine enhanced immune responses to i.p. or i.v. injected SRBC. Similarly C. parvum injected i.p. prior to i.v. immunization resulted in an augmented anti-SRBC response. An enhancement of anti-SRBC response was also noted when C. parvum was injected i.p. on the day of i.p. immunization. The suppressed responses in C. parvum injected animals could be explained partly by the reduced splenic localization of the antigen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The biosynthesis of PGE2 and PGF2alpha was measured in intact peritoneal exudate preparations obtained from C. parvum-treated and control C3H mice. Although both the control and stimulated preparations biosynthesized PGF2alpha and PGE2 from [1-14C] arachidonic acid, the stimulated preparations generated more of both prostaglandins than did nonstimulated preparations, probably as a result of increased synthesis within macrophages. Increased transformation of PGE2 into PGF2alpha by PGE2 9-ketoreductase was noted in stimulated preparations when compared to that in control cells. The data suggest that stimulated macrophages are capable of generating increased quantities of PGF2alpha and therefore might function as one source of this substance in resolving inflammatory reactions.
Corynebacterium parvum administration in CBA mice resulted in the stimulation in the peritoneal exudate and other lymphoid organs of cells which nonspecifically inhibited the tumor growth in vitro. The distribution of the antitumor activity in different organs was dependent on the route of C. parvum injection. Both ip and iv treatments stimulated antitumor activity in the peritoneal exudate, whereas the sc route was ineffective. Only iv treatment stimulated the antitumor activity in the blood, and only the sc route produced the antitumor activity in the lymph node. The antitumor activity following the sc treatment was confined mainly to nodes draining the site of C. parvum injection. All routes of treatment provoked some antitumor activity in the spleen, although the degree of the activity varied with the route in the order of ip, iv, and sc. The antitumor activity in all organs peaked between 4 and 14 days after C. parvum injection. This activity in all organs, except the spleen, disappeared by day 42 post treatment. The results are discussed in the light of the in vivo observations on the antitumor effects of C. parvum.
The radiosensitivity of three forms of response to injection of C. parvum in mice has been investigated. The increase in phagocytin index evoked by IP or IV injection of 0.7 mg C. parvum (but not that evoked by 1.4 mg) was reduced but not abolished in mice given 350-500 rad whole-body irradiation 4 days before C. parvum injection. Irradiation (500-1,000 rad) 4 days after C. parvum injection had no such effect. The antitumour cytotoxicity in vitro of PE and spleen cells from C. parvum-treated mice was abolished by irradiation of the cell donor (400-800 rad) 4 days before C. parvum injection, but was not reduced by irradiation (800 rad) of the cell donor 4 days after C. parvum injection or of the effector cells in vitro. The antitumour response to systemic (IP) injection of C. parvum was reduced by 350-500 rad whole-body irradiation, irrespective of whether this was given 4 days before or 4 days after C. parvum injection. The response to intratumour injection of C. parvum was even more radiosensitive. It has been suggested in previous papers from this laboratory that the antitumour effect of C. parvum is related to its capacity to stimulate macrophage activity, although in addition T lymphocytes are necessary for local injection to be effective and non-T lymphocytes may be concerned in the response to both local and systemic injection. The present results in no way conflict with this view. They suggest in addition that the effect of C. parvum on the macrophage system is, to a considerable extent, due to stimulation of macrophage precursors to differentiate into actively phagocytic and cytotoxic mature cells.
S.c. injection of tumour cells or small pieces of tumour irradiated to a dose of 22,000 rad evoked resistance to live challenge with the same tumour (a CBA strain fibrosarcoma induced with methylcholanthrene) 14 days later. This resistance was, however, over-ridden if the challenging inoculum was sufficiently large, and did not develop if the cells were irradiated to 100,000 rad. The resistance evoked by injection of 10(6) irradiated tumour cells was impaired by i.p. injection of 1-4 mg C. parvum 5 days before, and virtually abolished by a similar injection 11 days after, the irradiated cells. The effect of s.c. injection of a mixture of 10(6) irradiated cells and C. parvum 14 days before live challenge depended on the dose of C. parvum. With 0-7 mg the development of resistance was largely but not completely abrogated; 0-35 mg resulted in a lesser degree of abrogation, and 0-09 mg or 0-02 mg had little or no effect.
Explore the source record for details and available documents.
Antibody-dependent (K cell) cytotoxic activity of spleen cells from mice bearing a chemically induced fibrosarcoma has been studied by using antibody-coated chicken erythrocytes as target cells. Spleen cells from tumor-bearing animals caused a significantly greater degree of target cells destruction than did those from control animals. The elevated cytotoxic activity in tumor-bearing animals increased with time after the tumor inoculation and correlated directly with the size of the tumor. The development of increased cytotoxic activity could be circumvented by surgical removal of the tumor. Mice that received x-irradiated tumor cells of x-irradiated tumor cells followed by a live challenge did not show a tumor growth and also failed to show increased K cell cytotoxic activity. It has been concluded that the increased K cell activity results directly from the active growth of tumor. The role of K cells in immunosurveillance has been discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Administration of C. parvum to both intact and thymectomized mice resulted in the appearance in the peritoneal exudate of cells which inhibited tumour growth in vitro. This effect was mediated by intact, viable adherent cells, which it seems reasonable to categorize as macrophages, and was contingent on contact between the effector and target cells. No co-operation was observed between lymph node cells from C. parvum treated mice and peritoneal exudate cells from normal mice.
Pulmonary blastoma is a rare primary malignancy of the lung originating from multipotential pulmonary blastema. Two cases of this tumor are reported emphasizing lack of correlation between the microscopic appearance and the clinical course. There are no specific clinical features that differentiate this tumor from the more common lung neoplasms. Surgical resection is the preferred treatment; the merits of radiotherapy and chemotherapy have not yet been established. Prognosis after adequate resection appears no better than for other pulmonary malignancies.
Various strains of anaerobic coryneforms and the closely related Propionibacteria have been compared in vivo with respect to their anti-tumour activity. Their effectiveness has been correlated with their serological relationship and to some extent with their ability to stimulate the lymphoreticular system. Organisms belonging to Corynebacterium acnes groups I and II and C. avidum group IV were active anti-tumour agents, although of varying effectiveness. These strains are serologically closely related and all produce a soluble cross-reacting antigen. The single C. granulosum group III strain which we tested, an unclassified coryneform, and the classical Propionibacteria did not cross-react with the main group and had little or no anti-tumour activity. At the high dose (0.7 mg) we used, all strains, whether they inhibited tumour development or not, enhanced clearance of colloidal carbon and stimulated production of an inflammatory peritoneal exudate; at lower dosage the results were too variable to permit valid comparison. At the higher dose anti-tumour activity of a strain appeared to correlate best with ability to produce splenomegally and decrease red cell volume in the blood.