James Harlos - Academia.edu (original) (raw)

Papers by James Harlos

Cell Biochem Biophys, 1990

Mechanical trauma appears to be one significant cause of the rapid intravascular death of cancer ... more Mechanical trauma appears to be one significant cause of the rapid intravascular death of cancer cells and, as such, could act as an important rate regulator for the metastatic process. Intravascular mechanical trauma to cancer cells is thought to be a consequence of shape transitions, occurring when they are deformed from spherical shape by entry into, and passage along, capillaries having smaller diameters than themselves. These transitions from spherical shape require increases in surface area; first, an apparent increase in surface area is accomplished by a reversible, nonlethal surface membrane unfolding. If this is insufficient to meet geometric demands, it is followed by a true increase in surface area, resulting in increased tension in the cancer cell surface membrane, leading to its lethal rupture.

British Journal of Cancer, 1991

Dormant and regressing implants of C3H mammary carcinoma MC2 were always found to be surrounded b... more Dormant and regressing implants of C3H mammary carcinoma MC2 were always found to be surrounded by a cellular fibrous capsule where macrophages and T cells predominated as the cellular elements. Macrophages were always closely associated with the collagen deposition, and stained with anti-collagen type I immuno-peroxidase in tissue sections. The capacities of macrophages and T-lymphocytes to function in collagen formation was investigated with the use of Nuclepore chambers implanted i.p. in normal mice. The procollagen that entered the chambers via the pores, was assumed to have been produced by the packed layer of peritoneal macrophages that adhered firmly to the outside of washed chambers. The adherent cells all stained with Mac-I immuno-peroxidase, and phagocytosed yeast in short-term culture. The formation of collagen fibres in the chambers was enhanced if the chambers contained T lymphocytes. It appears that macrophages have the capacity to function as collagen producing cells in tumour encapsulation.

Cancer research, Jan 15, 1987

The normal incidence of metastasis was determined in 207 C3H/He and 42 C3Hf/He mice with spontane... more The normal incidence of metastasis was determined in 207 C3H/He and 42 C3Hf/He mice with spontaneous mammary tumors. The effects of early versus delayed surgical removal of the tumors on the incidence of metastasis were studied in the C3H/He mice. The presence of metastases was determined by histological examination, primarily of the lungs. The incidence of metastasis was proportional to the size the primary tumors were allowed to reach before surgery, with the highest incidence in mice not surgically cured. Tumors that developed early in the life of the mice had the greater tendency to metastasize. Immunogenic and non-immunogenic tumors occurred with similar frequency among 16 metastasizing tumors tested. Primary tumors and their metastases were equally immunogenic. All of 95 metastasizing adenocarcinomas grew extensively within pulmonary vessels with no tendency for active extravasation. In contrast, each of six metastasizing mammary sarcomas extravasated actively and probably ext...

Cell Biophysics, 1979

When lymphocytes from a majority of patients with cancer are incubated with encephalitogenic fact... more When lymphocytes from a majority of patients with cancer are incubated with encephalitogenic factor, a lymphocyte product is released that reduces the anodic electrophoretic mobilities of guinea pig macrophages and fixed, tanned sheep erythrocytes. Although these reactions are not specific for cancer, it is distinctly possible that in patients with cancer, products from stimulated lymphocytes are capable of altering the surfaces of the patients' own macrophages, thereby modifying the course of their disease. In this paper, we attempt to elucidate some mechanisms for the binding of lymphocyte products to macrophages, such as occurs in the macrophage electrophoretic mobility (MEM) test, since this may be of general interest. Binding of lymphocyte product to macrophages has been monitored by measurements of their electrophoretic mobilities and by electron microscopic determination of the density of binding of electron-dense, cationic colloidal iron hydroxide particles to their surfaces. The results show that the lymphocyte products reduce the net surface negativity of the macrophages by (coulombic) binding of this net positively charged material to sialic acids at the macrophage surface. Product-binding can be prevented by prior treatment of the macrophages with neuraminidase. It appears that only a minority of sialic acids are involved in the binding process, which occurs without demonstrable blocking of adjacent sialic acids or redistribution of such sites over the macrophage surface. Parallel experiments with fixed tanned erythrocytes also suggest that binding of lymphocyte products is not solely determined by surface sialic acids, although it cannot occur without them.

Progress in Surface Science, 1972

Intercellular Communication, 1977

Biorheology, 1991

Ehrlich ascites cancer cells were compressed between glass microscope slides by the addition of w... more Ehrlich ascites cancer cells were compressed between glass microscope slides by the addition of weights. The projected areas of the cells were measured, and their surface membrane integrity determined by means of trypan-blue exclusion tests under different compression loads of 0 to 800g. The results are compatible with a two-step mechanism for surface rupture; first the cell membrane is unfolded and then stretched, with modest degrees of stretching associated with membrane rupture. It is calculated that lethal surface membrane rupture of the type produced here by compression, could also be produced when cancer cells are deformed by entry and passage along relatively non-deformable capillaries. This would at least partially account for the rapid destruction of cancer cells in the microcirculation. The observation that isolated nuclei are less deformable than whole cells, may indicate that their nuclei may protect cancer cells from biomechanical trauma.

Cancer research, 1979

Walker 256 cancer cells growing in the ascitic form and following direct injection in the livers ... more Walker 256 cancer cells growing in the ascitic form and following direct injection in the livers and in s.c. sites in rats had significantly higher anodic electrophoretic mobilities than did cells derived from the same source but growing in kidneys and spleens. Following incubation with neuraminidase, the cancer cells from the kidneys and spleen lost significantly less net surface negativity than did cells growing in the other 3 sites. These kidney-and spleen-associated differences were not demonstrably due to preexisting, electrokinetic subpopu lations of cancer cells within the original ascites tumor; they were maintained on organ-to-organ passage and were reversed on reconversion of the tumors to ascitic form. The evidence favors site-induced modulation to account for the differences between primary cancers and their metastases are conceivably due to site-induced modulation as distinct from preexisting metastatic subpopulations. Evidence which will be discussed later suggests that the cancer cells in some primary tumors are different from those in their metastases in at least some organs. The nonexcbusive possibilities arise of whether these organs were selectively seeded by preexisting subpopulations of cancer cells from within the primary tumor or whether the seeding was random. In either case, the cells in the metastases were different be cause they were located in specific metastatic sites.

Journal of Theoretical Biology, 1972

The Journal of Pathology, 1986

This communication concerns the statistical significance of negative reports, when solid organs a... more This communication concerns the statistical significance of negative reports, when solid organs are examined for metastases deep to their surfaces, by standard slicing techniques at necropsy. By taking into account factors influencing tumour detection including slice thickness, metastatic tumour size and number, the probabilities of incidence of false negative reports may be calculated and values for the undetected tumour bulk may be obtained. A graph is reproduced which facilitates the assessment.

International Journal of Cancer, 1986

The surface charge densities of Lewis lung carcinoma (3LL) cells were measured in tumors transpla... more The surface charge densities of Lewis lung carcinoma (3LL) cells were measured in tumors transplanted into subcutaneous (s.c.) sites, and into the kidneys (K), as well as in kidney tumors transplanted to, and maintained in, the s.c. site (K.s.c.). K cells showed a significant increase in net negativity in comparison with s.c. cells, which was stable over II passages. On back-transplantation of K cells to the s.c. site, the net negativity of K.s.c. cells was higher than that of the s.c. cells, but the increase was stable for only 7 passages; on subsequent passages the net negativity fell, approaching that of the s.c. cells. Detailed analyses suggest the presence in these tumors of 2 subpopulations of 3LL cells, whose proportions change in the different sites studied to produce changes in the mean electrophoretic mobilities of the whole cancer cell populations. The altered proportions of the 2 cell types in the 3 sites were not associated with major changes either in their general behavior with respect to metastasis, or in differential growth in various organs following s.c., tail vein, and left ventricular injections. Selection induced by growth in the kidney, as evidenced by physiochemical changes at the cancer cell surface, was not associated with kidney preference in metastasis or metastasis-related behavior.

International Journal of Cancer, 1983

The peripheries of Lewis lung(3U) tumor cells growing in different organs of the mouse were studi... more The peripheries of Lewis lung(3U) tumor cells growing in different organs of the mouse were studied by cell eltrophoresis and electron microscopic quantitation of colloid iron hydroxide (CIH) adsorption before and after incubation with neuraminidw. The results show that cells growing in the kidney after direct injection have significantly higher anodic mobilities than cells growing in the subcutaneous sites from which they were derived, or in intramuscular sites, liver or spleen. The proportional contributions of cell surface sialk acids were similar in all sites. Electron microscopy of cells reacted with CIH indicates that the increased surface charge density of the tumor cells growing in the kidney is due to the presence of increased densities of non-ClH-binding ionogenic groups. Before neuraminidase treatment, the surface distribution patterns of CIH were indistinguishably random for 3 U cells growing in all sites. After neuraminidw treatment, significantly more clustering of CIH padcles was observed on 3 U cells with a history of growth in the kidney than in subcutaneous sites. The changes observed in the 3 U cells growing in the kidney were irreversibh, and persistnd on multiple back-transplantation to subcutaneous sites. Detailed analysis of the results shows the changes to be due to the preferential selection of a subpopulation consisting of approximately 10% of the original (subcutaneous) tumor-cell populaton. This evidence for M irreversible site-induced selection of a pre-exhting subpopulation of 3 U cells contrasts with the reversible (modulation) site-induced adaptaHonpreviourly observed by us in Walker-256 cancer cells, and therefore indicates that both selective and adaptive proccrrcr can occur. Even in the case of the 3 U cells, site-spacinc selection is not general, since the changes were observed in tumors growing in the kidney but not in the other anatomic sites. At present we cannot comment on the relevance of these reported changes to naturally occurring metastasis. '

International Journal of Cancer, 1987

The local and systemic therapeutic effects of multiple peritumoral injections of recombinant huma... more The local and systemic therapeutic effects of multiple peritumoral injections of recombinant human interleukin-2 (IL-2) were tested against the syngeneic, immunogenic mammary carcinoma MC2 implanted subcutaneously into C3H/He mice. Multiple (12) low-dose injections had a greater local therapeutic effect than the same total amount of IL-2 given in 2 injections. Peri-tumoral injections were equally effective in inhibiting the growth of the injected tumors in normal and in immunized mice. The systemic therapeutic effect was manifested by the inhibition of tumors implanted contra-laterally to the injected tumors, and was only discernible in non-immunized mice.

International Journal of Cancer, 1984

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied follo... more The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B 16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor-bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the"roil" effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the "mechanical" hypothesis.

International Journal of Cancer, 1978

When peripheral lymphocytes from patients with a history of cancer are incubated with encephalito... more When peripheral lymphocytes from patients with a history of cancer are incubated with encephalitogenic factor (EF), in 90% of cases the resulting products reduce the net surface negativity of guinea-pig macrophages, used as detector cells, as revealed in the macrophage electrophoretic mobility (MEM) test. The MEM test is positive in 36% of people with no history of cancer. Formaldehyde-fixed tanned sheep erythrocytes have been used as detector cells in place of guinea-pig macrophages, in afixed tanned erythrocyte electrophoretic mobility (FTEEM) test, with lymphocyte products identical to those used in M E M tests. In patients with a history of cancer, positive results were obtained in 28/42 cases with the FTEEM test compared with 32/42 in the MEM test. In people with no history of cancer, negative results were obtained in 16/18 cases with the FTEEM test, compared with 12/18 in the MEM test in the present series, and 51/69 in a more extensive series. These differences are not significant. Cases in which discrepancies are revealed between the two tests are discussed in terms of individual case histories.

International Journal of Cancer, 1977

The macrophage electrophoretic mobility (MEM) test was performed on guinea-pig macrophages treate... more The macrophage electrophoretic mobility (MEM) test was performed on guinea-pig macrophages treated with the interaction products of encephalitogenic protein and peripheral lymphocytes from 44 patiefits with colorectal cancer and 33 healthy" controls. I n 54/60 tests involving patients, statistically significant reductions in electrophoretic mobilities were observed, compared with 12/33 in controls. O u r overall results on the reductions in Encephalitogenic factor (EF) This material was Prepared from fresh human brain, obtained at autopsy, by sequential chloroform/ methanol and acid extractions, according to the method of Kies (1965) which is similar to that used by CaSParY and Field (1971) for their preparation of EF. The final extract was stored at-80" C at a conmacrophage mobilities by lymphocyte products are in accord with the work of some other workers, but not all. In contrast to many other studies, the standard procedures used here to express the results should permit an exchange of data on an international basis and allow a more rapid, general appraisal of the M E M test. Macrophage preparations Female Camm-Hartley guinea-pigs (Camm Research Institute, New Jersey) weighing 500-800 g, were used in these studies. Animals received 20 ml sterile light mineral oil by intraperitoneal injection, 6-10 days prior to harvesting. Anesthetized guineapigs were exsanguinated by cardiac puncture, and macrophages were aspirated from the abdominal cavity following intraperitoneal injection of 100 ml

Biopolymers, 1971

The mechanism of the unique and specific association of a given amino acid to its t.-ltNA is inve... more The mechanism of the unique and specific association of a given amino acid to its t.-ltNA is investigated by theoretical methods. Several possible schemes are proposed t.o explain specificit.y. The physical forces which act wit.hin these mechanisms are illustrated by t,he computer simulation of probable int,eract.ions between glycine and nricleot,ide bases and base pairs. It is demonstrated that, glycine has direct and selective affinities for the riucleot,ide bases and 1 hat. these interact,ioris are principally determined by t,he polar groups. Energies have been oitlculat,ed for the int,eractioti of glycine wit.h several base pairs. From these, t.he possibility t,hat. spec:ificit,y arises t,hrough direct, complexing of an amino acid with its ant,icodon is evaluated.