Background. Although the biologic characteristics of papillary cystic tumors (PCT) generally indicate a good prognosis, a malignant form has been reported. Methods. Twenty-two examples of PCT were examined to assess their malignant potential by histologic, flow cytometric, and immunohistochemical studies. Results. Three had hepatic, peritoneal, and/or lymph node metastases (metastasizing tumors [MT]); the other 19 PCT had no such metastatic features (nonmetastasizing tumors [NMT]). Venous invasion was detected in all three MT and two NMT. Compared with the 19 NMT, the MT had a higher nuclear grade and more prominent necrobiotic nests characterized by aggregates of cells with pyknotic nuclei and eosinophilic cytoplasm. In the flow cytometric analysis of cellular DNA content, one MT was aneuploid, and eight NMT were diploid. Immunohistochemically, there was no difference between the MT and NMT. Conclusions. These results support the assumption that venous invasion, nuclear grade, and prominent necrobiotic nests are useful as histologic parameters to detect the malignant potential of PCT. Cancer 1993; 71:82-92.
Two children with stage III, IV sacrococcygeal yolk sac carcinoma were treated with cisplatin (CDDP), vinblastine (VBL), and bleomycin (BLM)(PVB therapy). One patient was a 1-year-6-month-old female having pulmonary and liver meatatasis, the other was a 1-year-9-month-old female with bilateral inguinal lymph node metastasis. In both, the blood levels of α-fetoprotein markedly decreased after 3 or 4 cycles of this therapy, and the tumors were resected.As maintenance therapy, the first patient received CDDP and adriamycin (ADM), and the second received CDDP+VBL because CDDP was considered to be the most effectie drug in this therapy, and from our experience in the treatment of advanced neuroblastoma, CDDP can be used up to a total dose of 1000 mg/m2 if attention is given to renal and auditory function, although VAC therapy and pulse VAC therapy had been used in some studies. The patients now have no evidence of disease.These results suggest that PVB therapy followed by active maintenance therapy with CDDP, ADM and VBL may be very effective for sacrococcygeal yolk sac carcinoma in children.
Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and systemic low dose rIL-2 effectively eradicates pulmonary metastases of the murine MCA-105 sarcoma. We described earlier that host CD8+ T cells are critical for tumor eradication and that successful treatment is associated with production of high levels of IFN-gamma and granulocyte/macrophage (GM)-CSF by donor TIL in vitro. Here, we propose the mechanism through which adoptively transferred Thy-1.1+ TIL induce a host antitumor response in congenic Thy-1.2+ tumor-bearing mice. Donor Thy-1.1+ TIL were detected at the tumor site 12 h after transfer. These Thy-1.1+ cells produced IFN-gamma and GM-CSF in situ. The percentage of Thy-1.1+ TIL at the tumor site increased up to 16.4 +/- 4.9% 24 h after transfer but decreased to undetectable levels thereafter. In contrast, the percentages of host cells producing IFN-gamma and GM-CSF continued to increase at the tumor site. These increases were significantly higher in TIL + rIL-2-treated mice compared with untreated mice and rIL-2-treated mice 48 h after TIL transfer. The appearance of IFN-gamma+ and GM-CSF+ cells was followed by a large influx of host CD4+, CD8+, and Thy-1.2+ TIL and eventually by tumor eradication. This response was tumor specific since TIL obtained from MCA-205 did not induce high levels of IFN-gamma and GM-CSF and did not induce tumor eradication of MCA-105 tumor. Coinjection of Thy-1.1+ TIL and anti-IFN-gamma or anti-GM-CSF mAb significantly inhibited antitumor efficacy of the TIL + rIL-2 treatment. We conclude that successful adoptive immunotherapy in this model is mediated through cytokine production by adoptively transferred TIL that induce a host T cell-dependent antitumor response.
A soluble beta-galactoside-binding lectin, galectin-3 has been shown to be involved in cell adhesion and activation of immune cells. Although galectin-3 is known to be expressed in various types of cells, it has not been shown whether galectin-3 is expressed in T lymphocytes. We present evidence here that galectin-3 is expressed in activated murine T lymphocytes including CD4+ and CD8+ T cells but not in resting T cells. Galectin-3 expression was induced by anti-CD3 mAb or mitogen and enhanced by common gamma-chain signaling cytokines, IL-2, IL-4, and IL-7, in activated T lymphocytes, whereas the inflammatory cytokines including TNF-alpha and IFN-gamma did not. Galectin-3 expression and proliferation were down-regulated by withdrawal of IL-2 and gamma irradiation. Antisense but not sense phosphorothioated oligonucleotides for galectin-3 inhibited galectin-3 expression and blocked proliferation of T cells significantly. This study suggests that up-regulation of galectin-3 plays an important role in proliferation of activated T lymphocytes.
Abstract Introduction Anti‐N‐methyl‐D‐aspartate receptor encephalitis is caused by auto‐antibodies that target the N‐methyl‐D‐aspartate receptor. Autonomic instability is a hallmark of the disease. The objective of this case series is to examine how anesthesia affects pediatric patients with this disease. Methods We performed a retrospective chart review of 28 records in 17 patients who underwent anesthesia. Our primary outcomes were hemodynamic changes during the perioperative period. Heart rate, systolic and diastolic blood pressures, respiratory rate, and oxygen saturation comprise our endpoints. A subgroup of patients, who underwent imaging with anesthesia, was then compared to controls. Results In anti‐N‐methyl‐D‐aspartate receptor encephalitis cases, there were significant percent changes from baseline in heart rate; median = −14.3%, 95% CI (−19.3, −9.0), p < .01 at 30 min and −15.7%, (−21.1, −9.8), p < .01 at 60 min; in systolic blood pressure, −19.4%, (−23.7, −14.8) at 30 min, p < .01, and −14.8%, (−19.7, −9.5) at 60 min, p < .01; in diastolic blood pressure, −41.9%, (−46.9, −36.3), p < .01 at 30 min, and −37.5%, (−43.4, −30.9), p < .01 at 60 min. When compared to controls, there were no significant differences between the two groups across time of anesthesia (baseline to 60 min) in heart rate ( p = .24), systolic blood pressure ( p = .30), and diastolic blood pressure ( p = .11). No patients experienced hemodynamic lability under anesthesia. One patient, with severe symptoms, died within 24 h of anesthesia. Conclusion Although pediatric patients with anti‐N‐methyl‐D‐aspartate receptor encephalitis experienced vital sign changes with anesthesia, they were not clinically significant and they behaved similarly to controls. Disease severity may be a risk factor for perioperative complications.
Previously we described that the adoptive transfer of tumor-infiltrating lymphocytes (TIL) + interleukin-2 (IL-2) leads to eradication of established methyl-cholanthrene (MCA)-105 fibrosarcoma pulmonary metastases in a congenic murine model. The in vivo efficacy of TIL was associated with their ability to secrete interferon-γ (IFN-γ), and to a lesser extent granulocyte-macrophage colony-stimulating factor. The local secretion of these cytokines resulted in recruitment of naive host immune cells to the tumor and eventually in a successful host antitumor immune response. In the present study, to further evaluate the role of IFN-γ in the induction of a host antitumor immune response, we compared the treatment efficacy of adoptively transferred T cells and IFN-γ gene transfected tumor cells (MCA-105/IFN-γ) as delivery systems of IFN-γ. Treatment with TIL-IL-2 or irradiated MCA-105/IFN-γ induced a similar reduction in pulmonary metastases of MCA-105 tumor. In contrast, irradiated wild-type MCA-105 or TIL from IFN-γ gene knockout mice did not cause tumor eradication. MCA-105 tumor-bearing mice treated with MCA-205/IFN-γ showed a partial reduction in the number of pulmonary metastases. Histologically, lungs of successfully treated mice showed that initially activated macrophages expressing inducible nitric oxide synthase (iNOS) and dendritic cells infiltrated the tumor bed. Subsequently, CD4+ and CD8+ T cells infiltrated tumors. The therapeutic efficacy of IFN-γ transfected tumor cells was eliminated when either CD4+ T cells or CD8+ T cells were depleted. These results suggest that local secretion of IFN-γ induces a tumor-specific host antitumor immune response mediated through activated macrophages, dendritic cells, and tumor-specific T cells. This may be a common component of successful immunotherapy.
Neuroblastoma has been recognized as the most common solid tumor of infancy and childhood. The occurrence of bilateral adrenal neuroblastoma, however, is extremely rare and only a small number of cases have been previously reported. The authors herein report the clinical, histopathological and molecular biological features of two bilateral adrenal cases out of 125 neuroblastoma patients treated at Kyushu University Hospital over a 35-year period. The clinical and histopathological data of the two cases of bilateral adrenal neuroblastoma were reviewed. In Case 1, which had multiple liver metastases, a post-mortem examination revealed bilateral adrenal involvement. In Case 2, which had been detected by mass screening, CT showed masses in both adrenal glands. No big differences in size were recognized between the tumors in either of the cases. A histopathological examination revealed rosette fibrillary type neuroblastomas in both cases. The DNA of these tumor samples stored at -80°C was extracted and the number of copies of the N-myc gene was determined by a Southern blot analysis. Fourteen copies of the gene were detected in Case 1, whereas neither of the tumors in Case 2 showed any amplification. The clinical outcome, histopathological findings and N-myc gene analysis of two cases might support the variety of biological features of this rare group of neuroblastoma.
