Bone metastases from gynaecological epithelial cancers.

The aim of this study was to investigate the clinical features and prognosis in patients with gynaecological epithelial cancers metastasised to bones. A total of 26 patients were studied retrospectively. Clinical and pathological data were analysed along with a follow-up. It was found that the interval from primary diagnosis of cancer until bony relapse varied between 0 and 163 months (31.4 ± 36.8). Bone metastases were solitary in 11 cases and multifocal in 15 cases. A total of 14 patients demonstrated only bony metastases while 12 had both bony and non-bony metastases. The time to follow-up from the diagnosis of osseous relapse varied between 1 and 43 months (10.0 ± 10.4). During follow-ups, 13 patients died and 13 patients survived. In both univariate and multivariate analyses, synchronous non-bony metastases and symptomatic treatment without oncological therapy impaired prognosis. It was concluded that even in the presence of multiple bone metastases, some patients may benefit from radiotherapy, chemotherapy or a combination of both, rather than palliative care alone, providing they do not have additional soft tissue metastases.

Central nervous system metastases from epithelial ovarian cancer.

The aim of the study was to assess the clinical features and prognosis in patients with epithelial ovarian cancer (EOC) metastasised to the central nervous system (CNS). A total of 15 patients were studied retrospectively. Clinical and pathological data and follow-up were analysed. It was found that at the diagnosis of primary EOC, the patients were 41-69 years old (56.6 ± 8.3). The interval from diagnosis of primary EOC until the relapse was 2-39 months (19.1 ± 10.5). Palliative radiotherapy was the treatment of the CNS relapse in 13 patients (86.7%). The follow-up after CNS relapse varied 0.5-15 months (4.7 ± 4.2). At the time of retrospective analysis, none of the patients were still alive. Multifocality of the CNS metastases, the presence of synchronous extracranial metastases and locations in the brain were not associated with survival. It was concluded that the development of the CNS metastases seems to be not uncommon in patients with advanced ovarian cancer. Despite oncological treatment, they are indicators of poor prognosis, and most of the patients do not survive beyond the first year of follow-up.

An extremely rare presentation of relapse in endometrioid endometrial adenocarcinoma: isolated metastases to the tibia and humerus. Case report and review of the literature.

In endometrial carcinoma patients, metastases to bones are rare and isolated metastases to extremities are extremely rare. We describe the case of a 59-year-old patient who underwent surgery followed by adjuvant radiotherapy due to endometrioid endometrial adenocarcinoma (grade 2, FIGO Stage II). After intervals of nine and 18 months respectively, she was diagnosed with metastatic tumours located in the right tibia and in the left humerus. The metastases were confirmed by biopsy. Following irradiation of metastatic lesions, the relief of symptoms was observed, and the patient remains under observation. We conclude that patients presenting a history of endometrial carcinoma with chronic pain in the extremities should be carefully evaluated, because although extremely rare, the carcinoma can metastasize to bones. Treatment of bone metastasis from endometrioid endometrial carcinoma by irradiation may increase quality of life and prolong survival.

Intracerebroventricularly transplanted embryonic neuronal tissue from inflammatory-resistant F344/N rats decreases acoustic startle responses in inflammatory-susceptible LEW/N rats.

Recently, we have shown that intracerebral transplantation of fetal F344/N hypothalamic tissue into LEW/N rats converts the LEW/N inflammatory-susceptible phenotype into an inflammatory-resistant phenotype in LEW/N hosts. Because LEW/N rats also exhibit relatively high acoustic startle responses (ASRs) compared to F344/N rats, in the present study we examined the effects on ASR of transplantation of F344/N hypothalamic tissue into the third ventricle of LEW/N rats. Dissected neuronal tissue from F344/N rats (Day E15-16) was implanted into the third ventricle of LEW/N rats. After 4 wk of postoperative survival, the animals' responses to acoustic startle stimuli were tested. Compared to naive and sham-operated animals, LEW/N rats transplanted with hypothalamic tissue exhibited significant decreases in ASR amplitudes. A similar decrease in ASR amplitude was observed in the group of LEW/N rats transplanted with embryonic striatal tissue. Our results indicate that the third ventricular neuronal grafts may modulate behavioral responses in the LEW/N rats. Although the mechanism of this effect is unknown, these studies suggest that intracerebral neuronal transplantation is a viable method with which to explore mechanisms of behavioral, neuroendocrine, and inflammatory response associations.

Increased value of E-rosette test in aseptic meningitis after incubation with CSF.

The influence of CSF on the active and total E-rosette test with peripheral blood (PB) lymphocytes of 12 children with aseptic meningitis (AM) was estimated. The control group included 10 children with convulsive fever. An increase in active and total T cells after incubation with CSF was observed in AM. This phenomenon might in part explain the higher proportion of T cells appearing in the CSF during aseptic meningitis. No changes were observed in the control group.

The estrogen antagonist tamoxifen inhibits carrageenan induced inflammation in LEW/N female rats.

Carrageenan induces a measurable inflammatory response in susceptible animals, and mature females are more responsive to carrageenan, than males. In the present study, we tested whether the estrogen antagonist tamoxifen influences carrageenan-induced inflammatory responses. Female LEW/N rats were treated with tamoxifen and compared to a control group of animals injected with vehicle. Tamoxifen significantly reduced estrous phase of estrous cycle during treatment, consistent with its functional anti-estrogen effects. Moreover, tamoxifen significantly decreased exudate volume but did not significantly influence relative white blood cell counts in the exudate. Interestingly, tamoxifen induced differential dose-dependent alterations in peripheral blood lymphocyte subpopulations. Low dose of tamoxifen increased CD25 cells. The high tamoxifen dose significantly increased CD8 blood lymphocytes counts. Our data indicate that tamoxifen treatment decreases carrageenan-induced inflammatory response in female LEW/N rats and suggest therefore that this inflammatory response is, at least in part, estrogen related. Moreover, our results suggest a possible role for tamoxifen in treatment of inflammatory disorders.

Inflammatory responses to carrageenan injection in LEW/N and F344/N rats: LEW/N rats show sex- and age-dependent changes in inflammatory reactions.

We studied the inflammatory responses of LEW/N and F344/N inbred rat strains after peripheral injection of carrageenan. The inflammatory responses were assessed in terms of volume, relative and total white blood cell counts of the exudates. Moreover, in both strains, blood CD4, CD8, CD25, naive CD4 (CD4/CD45RC) cell and B (CD45R) cell counts and plasma corticosterone levels, constituents of systemic inflammatory responses to carrageenan were evaluated. In general, LEW/N rats are highly responsive to challenge with carrageenan, whereas F344 rats are not. The strong local inflammatory responses to carrageenan are primarily exhibited by female LEW/N rats. The intensity of local inflammatory responses of LEW/N rats changes with the rat age, the highest exhibited by LEW/N rats up to 3 months of age, thereafter the carrageenan-induced inflammatory responses decline. Our results indicate that peripheral injection of carrageenan induces strong systemic immune component. After carrageenan injection, increases in CD8 and naive CD4 blood lymphocytes are seen. Although the carrageenan challenge does not change CD4 blood lymphocytes in both LEW/N and F344/N rat strains, LEW/N rats exhibit higher levels of CD4 cells than F344/N rats. Additionally, LEW/N rats demonstrated lower levels of B cells and higher naive CD4 lymphocytes. Carrageenan challenges induce significant increases in plasma corticosterone response in F344/N rats, as well as increases in LEW/N rats 1 h after injection. Our data stress the importance of rat age and gender in experiments studying inflammatory responses.

Intracerebroventricular transplantation of embryonic neuronal tissue from inflammatory resistant into inflammatory susceptible rats suppresses specific components of inflammation.

To more directly define the role of central nervous system factors in susceptibility to peripheral inflammatory disease, we examined the effect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in peripheral blood (a measure of the anamnestic immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats transplanted with hypothalamic tissue from inflammatory resistant Fischer (F344/N) rats exhibited > 85% decrease in carrageenan inflammation compared to naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham-operated animals. LEW/N rats transplanted with LEW/N hypothalamic tissue exhibited > 50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not affect the characteristically twofold higher percentage of naive versus memory T helper cells in LEW/N rats, suggesting that the central nervous system (CNS) and hypothalamus play a greater role in the innate inflammatory response than in the acquired immune processes. Grafted tissue survived well and did not show extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/N hypothalamic tissue also showed significant increases in plasma corticosterone responses to lipopolysaccharide. These data indicate that intracerebroventricular transplantation of fetal hypothalamic tissue from inflammatory resistant into inflammatory susceptible rats suppresses peripheral inflammation partially through hypothalamic factors. These findings have implications for understanding the contribution of specific neuronal tissue in regulation of components of the immune/inflammatory response and in susceptibility to inflammatory disease. Furthermore, this model could be used in the development of potential new treatments for inflammatory/autoimmune diseases aimed specifically at sites within the CNS.

Identification of a novel inflammation-protective locus in the Fischer rat.

Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N rats are relatively resistant to development of a wide variety of inflammatory diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs. F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10 that protects in a dominant fashion against the exudate volume component of innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be similar to one of the multiple regions found to link to inflammatory arthritis phenotypes in other crosses. The suggestive linkage on Chr 2 has not been previously reported and does not seem to contribute to this phenotype in the same manner as the QTL on Chr 10. These findings are consistent with the hypothesis that the innate exudate volume trait is a sub-phenotype of more complex inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage region could account for differences in this non-specific acute phase component of the inflammatory response. Since the rat Chr 10 exudate volume linkage region we have identified is syntenic with a region of human Chr 17 that has been shown to link to a variety of autoimmune/inflammatory diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of genes within this linkage region will shed light on genes relevant to the earliest inflammatory component and to susceptibility and resistance to such human autoimmune/inflammatory diseases.