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H Cravioto

Publications and source records attributed to H Cravioto.

At least 19 recordsLinked to original sources

Is polar spongioblastoma a tumor entity?

The distribution of cells in a parallel fashion with palisades of nuclei is common in neuroepithelial tumors. The authors have selected 16 such tumors from their series for study, as examples of different neuroepithelial oncotypes containing palisades of nuclei: three ependymomas, three hemispheric pilocytic astrocytomas, three oligodendrogliomas, three medulloblastomas, three cerebellar astrocytomas, and one central neuroblastoma. In two additional tumors, affecting a 12-year-old girl and a 51-year-old woman, this feature was present in the entire surgical specimen and the diagnosis was consistent with a polar spongioblastoma. This diagnosis applies in the literature to rate tumors of childhood and adolescence, both malignant and with embryonal features. In one specimen, a clear ependymomatous feature was found in a remote area of the tumor and in the other there were ultrastructural characteristics of neuroblastoma. Nuclear palisades can be found as local architectural features in many neuroepithelial tumors. The rare tumors diagnosed as polar spongioblastoma, according to published criteria, correspond to ependymomas and neuroblastomas. Polar spongioblastoma does not exist as a tumor entity.

Astrocytoma↗

Ependymoma: internal correlations among pathological signs: the anaplastic variant.

In a series of 298 cases of ependymoma, survival analysis identified some prognostic histological factors but failed to demonstrate a worse survival for the anaplastic variant diagnosed with the common criteria used for assessing anaplasia in primitive brain tumors. This finding suggests that either anaplastic ependymoma does not exist, or that the established criteria are not useful in its identification. To solve these problems, the association of histological, immunohistochemical, and ultrastructural signs in 173 intracranial cases was investigated and analyzed by means of contingency tables. Many signs had only focal distribution. Some signs, meaningful for anaplasia, such as very high cell density and number of mitoses, were found to be associated, whereas other signs usually considered indicative of anaplasia, such as endothelial hyperplasia, glomeruli, and necrosers, were not. In addition, pseudorosettes, mesodermic areas, and incomplete formation of perivascular pseudorosettes were signs associated with very high cell density and number of mitoses. Distribution of glial fibrillary acidic protein and vimentin, as well as other immunohistochemical and ultrastructural features, were not helpful, with the exception of microsettes found by electron microscopy. Our conclusion is that the anaplastic variant of ependymoma is recognizable only when some histological prognostic factors, such as cell density and number of mitoses, are maximally expressed.

Adolescent↗

Effect of difluoromethylornithine on the antiglioma therapeutic efficacy of intra-arterial BCNU.

In an attempt to improve glioma management, an animal model was developed to evaluate the therapeutic efficacy of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Furthermore, the model was used to study the antitumor activity of D,L-alpha-difluoromethylornithine (DFMO), a polyamine-biosynthesis inhibitor, used both as a single agent and in combination with intra-arterial BCNU. An N-methylnitrosourea-induced gliosarcoma (T9) was transplanted stereotaxically into the right caudate nucleus of male Fischer 344 rats. Animals receiving a single low-dose (5 mg/kg) intracarotid injection of BCNU 9 days following tumor implantation had a 57% increase in life span compared with untreated control rats (p less than 0.001). Intracarotid drug delivery was more effective than systemic (intraperitoneal) administration of the same dose of BCNU. When given as a single agent, DFMO demonstrated dose-dependent effectiveness. As part of a combined regimen, DFMO enhanced the antitumor therapeutic activity of both systemic (intraperitoneal) and intra-arterial BCNU. Survival times of animals receiving combined DFMO and intra-arterial BCNU were almost double those of untreated controls, and were significantly better than survival times of animals receiving combined DFMO and intraperitoneal BCNU. These findings suggest methods to optimize current clinical chemotherapy for glioma.

Animals↗

Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity.

The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10(5) gliosarcoma T9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10(5) T9 cells inhibited the growth of T9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T9 challenge doses up to 1 X 10(7) cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T9 challenge but not of EB-679, an unrelated glioma, in recipient rats. Rejection of IC T9 challenge was also obtained after IV transfer, in recipients of such "hyperimmune" spleen cells, but was less (60% maximum) than that noted after ID T9 challenge (100% maximum). The removal of B cells from the transferred spleen cells did not affect the results, suggesting that the specific immunity was mediated by T cells. We conclude that the special immunological circumstances of tumors growing in the brain renders them less accessible to rejection by systemically transferred immune cells, but it is nevertheless possible to effect a significant incidence of rejection of syngeneic tumor growth in the brain by the intravenous transfer of hyperimmune spleen cells.

Animals↗

Labeled putrescine as a probe in brain tumors.

The polyamine metabolism of transplanted N-nitrosomethylurea-derived rat glioma was determined with radiolabeled putrescine used as a marker for malignancy. The uptake of putrescine in vivo was complete within 5 minutes and was specific for tumor tissue. The conversion of putrescine to spermine and other metabolites by the tumor was rapid, in contrast to the case for adjacent normal brain. These results suggest that putrescine labeled with carbon-11 may be used as a positron-emission tomographic tracer for the selective metabolic imaging of brain tumor and may be used in an appropriate model as a marker for tumor growth rate.

Animals↗

Immunity to transplantable nitrosourea-induced neurogenic tumors. II. Immunoprophylaxis of tumors of the brain.

An effective method was sought to immunize rats against the growth of intracerebrally (IC) injected T9 tumor, a gliosarcoma cell line. Rats which were immunized with either 10(6) T9 cells mixed with 0.14 mg C. parvum, or 10(7) irradiated T9 cells showed tumor immunity to intradermal (ID) transplantation. However, to obtain tumor immunity to an IC challenge of T9 cells, rats initially had to reject an ID challenge of T9 cells. After sequential rejections of ID challenges of as many as 10(7) cells, a high degree of immunity was obtained, allowing rejection of up to 5 X 10(6) T9 cells injected IC. Spleen cells from highly immunized rats mixed with T9 cells at a ratio of 1:25 (tumor:spleen) destroyed T9 tumor cells in a Winn test. Normal spleen cells had no effect on tumor growth. We conclude that: 1) T9 cells are moderately immunogenic, 2) an effective method of immunization of CDF rats against ID transplanted T9 cells is 10(6) T9 cells with 0.14 mg C. parvum or 10(7) irradiated T9 cells, 3) a higher degree of tumor immunity is necessary to reach the brain than is needed to reach the periphery, and 4) spleen cells of highly immunized rats are cytotoxic to T9 tumor cells.

Animals↗

Hemangiopericytoma of the pituitary fossa: case report.

A case of hemangiopericytoma presenting as a sellar and suprasellar mass is reported. Although this is the first report of this tumor in such a location, it appears similar to hemangiopericytomas found in other locations.

Female↗

Serologic analysis of nitrosourea-induced rat gliomas.

Inbred CDF rats (cesarean-delivered F344 rats) were immunized with either a nitrosourea-induced glioma EA-285 or its subline EA-285A and both with and without Corynebacterium parvum. A humoral immune response in syngeneic rats to the immunizing tumor was demonstrated with micromodifications of different rosette assays (immune adherence assay, protein-A assay, and anti-C3-mixed hemadsorption assay). Extensive absorption studies of two immune sera with the highest reactivity revealed two glioma-specific antigens (or two components of one antigen) on the cell surface of the cloned tumor subline. One antigen was present only on the cell surface of the subline of the glioma used for both immunization and absorption analyses. The other antigen appeared on the cell surface of both the cloned subline EA-285A and the parental cell line EA-285. These preliminary studies showed that CDF rats immunized against a syngeneic glioma mounted a humoral immune response that appeared to be individually tumor-specific.

Animals↗

Clinical and ultrastructural study of painful neuroma.

A clinical and light and electron microscopic study of three cases of painful neuroma, surgically resected, was made. It was found (a) that painful neuromas contain large numbers of small diameter, unmyelinated fibers, in an apparently much larger proportion than myelinated fibers and (b) that a consistent, unrestrained growth of perineurial cells parallels the constant regeneration of axis cylinders. This results in the unabated formation of large numbers of "nerve minifascicles" growing in a chaotic fashion. Degeneration of axis cylinders and/or of myelin is minimal. It is suggested that the increased numbers of unmyelinated axis cylinders in traumatic neuromas could be related to the painful symptoms in some patients. It is further postulated that the unrestricted growth of perineurial cells is an attempt to contain the regeneration of axis cylinders and that the maintenance of perineurial integrity by fascicle ligation is important in the relief of painful human neuromas.

Adult↗

Neuroma formation and prevention by fascicle ligation in the rat.

Light and electron microscopic studies of the cut sciatic nerve in the rat showed typical neuroma formation. If the nerve was cut and the proximal segment was ligated as a whole, the neuromatous process appeared to be even more severe than that in the simply cut nerve. When the perineurium of the cut nerve was kept intact by fascicle ligation, the axonal regenerative process seemed to be altered significantly, and less neuroma formation occurred. The mechanism by which fascicle ligation limits axonal regeneration is unknown, but could involve peripheral as well as central mechanisms. Such a limitation of neuroma formation by fascicle ligation as was found in the rat might also apply to painful human neuromas.

Animals↗

In vitro transformation of fetal brain cells from CDF rats exposed in utero to N-ethyl-N-nitrosourea: morphologic and immunologic studies.

Inbred CDF rats received 250 mg N-ethyl-N-nitrosourea (ENU)/kg body weight in monosodium phosphate buffer (pH 5.5) during late pregnancy (18-21 days). Control rats received only buffer. One hour after ENU or buffer administration, the fetuses were delivered and fetal brain cells (FBC) were put in long-term tissue culture. Cell growth consisted of monolayers of glial, fibroblastic, and epithelial-like cells. FBC from buffer-treated rats could not be subcultured for more than 13-15 passages; only one culture was maintained up to the 26th passage. FBC from ENU-treated rats showed in vitro malignant transformation beginning at the 8th passage (100 days). Injection of these cells sc into irradiated or neonatally thymectomized syngeneic rats induced small palpable tumors that regressed completely by 15-28 days. Small nonprogressively growing subcutaneous tumors in normal rats, however, were obtained only after the 19th in vitro passage (200 days). These transformed FBC appeared highly antigenic. Tumor-associated antibody was demonmmune adherence assays. Rats immunized with irradiated malignant FBC showed rising tumor antibody titers. The antibody was absorbed by ENU-exposed FBC but not by normal fetal or adult syngeneic brain cells. We concluded that ENU-exposed cells become malignant when grown in vitro for at least 8 passages (100 days) but grow in vivo in X-irradiated or neonatally thymectomized rats only. These antigenic and tumorigenic clones may be selected in vitro, where they grow readily in the absence of immune resistance.

Animals↗

Immune surveillance and tumors of the nervous system.

The theory of immune surveillance postulates that one function of the immune system is to eliminate small numbers of malignant cells that arise spontaneously within the organism. Although there has been a great deal of both clinical and experimental evidence in favor of thistheory as it applies to general oncology, the question of whether or not such a surveillance system would be effective for tumors arising within the nervous system has never been studied. The young of pregnant rats which had been exposed to the neurocarcinogen ethylnitrosourea (ENU) were divided into control, immunosuppressed, and immunoenhanced groups. These lifetime alterations of the immune system had no effect on the course of nervous system tumor fromation. We believe that the most likely explanation for our results is that the "immunological privilege" of the brain prevents the usual interaction of the neoplasm and the immune system from occurring.

Animals↗

Desmosterol in human and experimental brain tumors in tissue culture.

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Animals↗