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Biomedical subjects

Y Sawamura

Publications and source records attributed to Y Sawamura.

At least 163 records · Page 9Linked to original sources

[A case of spinal cord glioblastoma multiforme].

A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of ureteral endometriosis; the usefulness of MRI for preoperative diagnosis].

A rare case of ureteral endometriosis is reported. A 46-year-old nulliparous woman was referred to our hospital because of right hydronephrosis which was detected by ultrasonography; Drip infusion pyelography showed right hydroureteronephrosis with the distal obstruction. MRI demonstrated right ovarian endometriosis and resultant ureteral stricture. Based on these findings, we made a preoperative diagnosis of right ureteral endometriosis. Right partial ureterectomy and ureteroureterostomy were performed. Pathological examination of the resected segment showed endometrial tissue around the ureteral lesion. She was administered LH-RH agonist (buserelin); her postoperative course was uneventful. IP showed no abnormalities 6 weeks after the operation. To our knowledge, this case is only the 55th case reported in the literature in Japan.

Endometriosis↗

[Immunotherapy of tumors of the central nervous system].

Malignant brain tumors are rapidly fatal and adjunction of chemo- and radio-therapy to surgical treatment has little changed their poor prognosis. The development of basic and clinical research in immunology of brain tumors has lead to new therapeutic strategies: 1) Humoral factors: Monoclonal antibodies (MAbs): alone or conjugated (to toxins, radionucleides or chemotherapeutic agents), MAbs can theoretically recognize antigens expressed by tumor cells and reach this target with high specificity. Large amounts of tumoricidal agents could be given to the tumor with low toxic effects to normal tissues. 2) Cellular factors: LAK cells: (lymphokine-activated-killer-cells) and activated TILs (tumor-infiltrating-lymphocytes) are autologous cytotoxic cells which can be produced by ex-vivo culture techniques and infused to the patient. These are very potent tumor-killer cells in vitro, however their in vivo effect is far less dramatic at the moment. 3) Cytokines: interferons, interleukins and other biological modifiers can act either directly on the tumor cells (cytotoxic effect) or indirectly through the modulation of the host-to-tumor response. 4) Combination of humoral and cellular factors: bispecific monoclonal antibodies are hybrid-molecules built from two different MAbs which can recognize two different targets, usually a tumor antigen on one hand and the T-cell-receptor (T 3) on the other hand. This combination of humoral and cellular effectors can theoretically lead to a preferential binding of effector cells to the tumor. All these new techniques are extensively studied in research laboratories and clinical trials without clear therapeutical benefit for the moment.

Antibodies, Monoclonal↗

[Cavernous hemangioma of the spermatic cord: a case report].

Cavernous hemangioma of the spermatic cord is a very rare disorder. A 26-year-old man was admitted to our hospital with chief complaints of right intrascrotal mass and hematospermia on October 19, 1990. Physical examination revealed a hard, non-transilluminated mass in the right spermatic cord. The mass was resected via the groin. Pathological examination showed cavernous hemangioma. The patient's postoperative course was uneventful. This is only the fourth case of cavernous hemangioma of the spermatic cord to be reported in the literature in Japan.

Adult↗

Combined cisplatin and radiation therapy for advanced bladder cancer.

Since September 1985, 44 patients with advanced urinary bladder cancer have been treated by combined cisplatin and full-dose radiotherapy. The patients were 32 males and 12 females, and their ages ranged from 33 to 83 years, with a median of 67.4 years. Radiotherapy consisting of a tumor dose of 50-60 Gy was administered with cobalt-60. Cisplatin was infused 5 days at a daily dose of 20 mg on the 1st and 4th weeks of treatment. Of the 39 evaluable patients 27 (69.2%) achieved a complete response. Toxicity was also evaluated for those 44 patients. Mainly gastrointestinal toxicity was noted: loss of appetite in 28 (64%), nausea and/or vomiting in 21 (48%), and diarrhea in 8 (18%). Leukocytopenia was noted in 16 (33%) and mild thrombocytopenia in 5 (11%). Mild dermatitis was noted in 8 (18%).

Aged↗

Antiproliferative effect of trapidil on PDGF-associated growth of human glioma cell lines in vitro.

The effects of trapidil on platelet-derived growth factor (PDGF)-associated growth of glioblastoma cells were studied. The assessment using PDGF-dependent rat lung endothelium cells revealed secretion of a PDGF-like factor from SF-126 cell line but not from SF-188. Human recombinant PDGF stimulated proliferation of both these glioblastoma cell lines. The anti-PDGF monoclonal antibody inhibited the growth of SF-126 more than SF-188. The results suggest the presence of an autocrine growth mechanism in SF-126 cells mediated by PDGF. The growth of both SF-126 and SF-188 cells was suppressed by trapidil, a specific PDGF antagonist, at 10 and 50 micrograms/ml, respectively. The proliferative response to exogenous PDGF and the antagonistic effect of trapidil were greater in the SF-126 cell line. In addition, trapidil markedly reduced production of prostaglandin E2 in both glioblastoma cell lines. This anti-proliferative effect on malignant glioma cells suggests that trapidil might be a new therapeutic agent for malignant gliomas.

Animals↗

[Ewing's sarcoma in the retroperitoneum].

The patient was a female aged 18. Hematuria was discovered at an examination two years previously at which time the patient was complaining of right lumbar pain. The patient visited our hospital with a chief complaint of right abdominal tumor in June, 1988. A retroperitoneal tumor, 77 X 45 mm in size, was observed by CT and ultrasonic examination, and the right kidney was in hydronephrosis. An operation was performed in September, 1988, based on a diagnosis of retroperitoneal tumor and hydronephrosis. The tumor was seen to have involved the right ureter. Subsequently the tumor was surgically removed; right total nephroureterectomy and partial cystectomy were performed at that time. The removed tumor was 90 X 70 mm in size and 120 g in weight; it was histopathologically diagnosed as extraskeletal Ewing sarcoma. A systemic examination was carried out postoperatively, but no abnormalities were observed. As of September, 1990, the patient had had no recurrence and was being kept observation on an outpatient basis. There have been a total of 210 case reports regarding extraskeletal Ewing sarcoma published worldwide, including our case and 26 cases in Japan, so far as we know. However those of a lesion of retroperitoneal origin are extremely rare, numbering only 11 cases worldwide and 2 Japan. Herein we report our case of extraskeletal Ewing sarcoma with reference to the other 209 cases reported in the literature to date.

Adolescent↗

[Isolation and expansion of glioma-infiltrating lymphocytes in vitro: an analysis of their surface phenotypes and antitumor activities].

The present study was conducted in order to examine the feasibility of isolating and growing glioma-infiltrating lymphocytes in vitro as possible effector cells for use in an adoptive immunotherapy. Thirty surgical specimens obtained from patients with malignant astrocytomas were studied. The glioma-infiltrating lymphocytes were separated from tumor tissue, expanded in the presence of interleukin-2, and evaluated their anti-tumor activities in vitro. Eighteen of 30 cultures of glioma-derived lymphocytes expanded with a substantial increase in cell numbers, of at least 5 x 10(8) cells up to 5 x 10(9), 4 to 8 weeks after the initiation of culture. The expanding glioma-derived lymphocytes consisted of 88 +/- 10% CD3+ T cells including both CD4+ and CD8+ subpopulations. CD16 was expressed on 4 +/- 5% of the cells and three cultures studied exhibited 14% +/- 1 of CD56+ cells. After 4 to 8 weeks of the proliferation period, the lymphocytes ceased to grow in all cultures. The glioma-derived effector lymphocytes could lyse almost all the autologous tumor targets as well as allogeneic glioma cells. The cytotoxic activity of the glioma-derived lymphocytes appeared to be similar or inferior to that of interleukin-2-activated peripheral blood lymphocytes obtained from the same patients in killing autologous glioma cells. The glioma-derived effector cells could also lyse three-dimensional glioma targets (spheroids), but this lytis activity was clearly lower than that of the activated peripheral blood lymphocytes. Ability of these effector cells to infiltrate glioma tissue was doubtful, since after 24-hours coculture of effector cells with target spheroids, the effector cells scarcely infiltrated the spheroids. In summary, glioma-derived lymphocytes expanded in bulk culture with interleukin-2 consisted predominantly of T-lymphoblasts with the ability to kill autologous glioma cells and also to lyse glioma spheroids. However a benefit of use of the glioma-derived lymphocyte as a novel effector cells in clinical trail replacing the IL-2-activated peripheral blood lymphocytes could not be found.

Adult↗

Arteriovenous malformation in meningothelial meningioma: case report.

An unusual association of a meningioma and an arteriovenous malformation is reported. A 68-year-old man developed left homonymous hemianopsia, left hemiparesis, and gaze palsy. Magnetic resonance imaging showed a right occipital mass lesion containing multiple signal-void areas with tubular and honeycomb appearance, suggesting a marked vascular component. An angiogram showed abnormal vasculature in the mass supplied by the posterior cerebral artery and a dural arteriovenous malformation on the tentorium. Neuropathological examination after total removal of the mass revealed a meningothelial meningioma including major portions of an arteriovenous malformation that extended from the dura and leptomeninges, through the meningioma, and into the occipital lobe, where the tumor was located.

Aged↗

[A case of prostatic hyperplasia in a young male].

Prostatic hyperplasia in young males is a very rare disease. A 28-year-old man was admitted to our hospital on June 24, 1989, with the chief complaints of intermittent macrohematuria and dysuria. Endoscopic examination revealed two papillary tumors in the prostatic urethra; no urinary bladder tumor was found. A transurethral resection was done for the urethral tumors. Pathological examination revealed prostatic hyperplasia. These lesions were considered ectopic prostatic tissue at first. However, imaging showed that this may in fact be prostatic hyperplasia of the apical region near the capsule. The post-operative course was uneventful and he is presently observed as an outpatient. This patient represents the seventh case reported in the literature.

Adult↗

Human glioblastoma cells release interleukin 6 in vivo and in vitro.

This study demonstrates interleukin 6 (IL-6) production and release by human glioblastomas. Twenty glioblastoma cell lines were tested for IL-6 bioactivity using an IL-6-dependent cell line (7TD1). All of the lines tested with one exception (LN-229) constitutively released IL-6. A significant induction of IL-6 production and secretion was observed when LN-229 cells were treated with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha. Various amounts of IL-6 mRNA were found in five of six cell lines tested. IL-6 mRNA was detected in line LN-229 only when the cells were treated with IL-1 beta or tumor necrosis factor alpha, confirming the bioassay data. Glioblastoma cells also produce IL-6 in vivo. (a) IL-6 activity was detected in 11 of 13 cerebrospinal fluids and five of five tumor cyst fluids. (b) IL-6 mRNA was found in four of four tumors. (c) Immunohistochemical analysis showed IL-6 within the tumor cells in 15 of 20 glioblastoma sections. In conclusion, biologically active IL-6 is released by almost all glioblastomas both in vitro and in vivo. The elevated levels of serum acute phase proteins and immune complexes found in glioblastoma patients may be the result of this secretion.

Glial Fibrillary Acidic Protein↗

Immunobiology of brain tumors.

In summary, many actual interactions between tumors in the CNS and the immune system have been demonstrated. The normal brain does not possess a lymphatic system and is partially hidden from the systemic immune system by the BBB, furthermore brain cells do not express MHC antigens which are necessary for the initiation of an immune response. In pathological conditions however, immunocompetent cells may find their way through transformed endothelial cells. Microglia and astrocytes may function as antigen presenting cells. Glioma cells when stimulated by cytokines such as IFN gamma can be induced to express MHC class I and class II antigens, thus making them more susceptible to an immune attack. In addition glioma cells are capable of secreting several cytokines including IL 1, IL 3 and IL 6 also involved in the generation of an immune response. Indeed, a functional analysis of lymphocytes infiltrating gliomas has revealed the accumulation at the tumor site of cytotoxic T lymphocytes as well as NK cells. However host-immune responses against gliomas seem to be weak in comparison to other cancers. Glioma cells are known to secrete TGF beta 2 and PGE 2 which may in part be responsible for this lack of immune response, thus shielding themselves from immune attack. In order to be recognized by the immune system the tumor cells must express TAA in addition to MHC antigens, and such TAA have been identified by MAbs. These MAbs can be used for "targeted" therapy when coupled to toxic agents or radionuclides. Preclinical studies have shown that, after intravenous or intracarotid injection, there is specific accumulation of the MAb in the tumor but in insufficient amounts for therapeutic use. The relatively small amount of MAb binding to the tumor in vivo can be due to several factors: not all the cells in a single tumor express a given tumor-associated antigens, the MAb may have a low affinity for the antigen, the BBB may hinder the passage of the MAb. Attempts have been made to overcome these drawbacks by opening the BBB for example. In addition MAbs can readily be used for the treatment of carcinomatous meningitis. There has been little success in the development of immunotherapy with IFN beta 1 and even less with adoptive immunotherapy using LAK cells plus IL 2. TIL as well as LAK cells can be expanded in vitro with IL2 and it is feasible to reinject these cells into the tumor site.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

In vitro prostaglandin E2 production by glioblastoma cells and its effect on interleukin-2 activation of oncolytic lymphocytes.

Glioblastoma cells constitutively produce various amounts of PGE2 (prostaglandin E2) in vitro. The amounts of PGE2 found in the conditioned medium of the glioblastoma cultures (less than 5 ng/ml) were not enough to inhibit the IL-2 (interleukin-2) activation of peripheral blood lymphocytes. However the amount of PGE2 produced by approximately 1 x 10(7) of the glioblastoma cells can be assumed to suppress the generation of IL-2-induced killing activity against glioblastoma cells.

Brain Neoplasms↗

Cavernous hemangioma in the cavernous sinus: case report.

The case of a middle-aged woman with a cavernous hemangioma of the right cavernous sinus who showed ipsilateral hemianopsia associated with contralateral blindness caused by left retrobulbar optic neuritis is presented. Total removal of the tumor was followed by recovery of the visual function of the right eye.

Cavernous Sinus↗

Influence of PGE2- and cAMP-modulating agents on human glioblastoma cell killing by interleukin-2-activated lymphocytes.

Human glioblastoma cells secrete factors, such as prostaglandin E (PGE) and transforming growth factor beta type 2, which are capable of suppressing several immune functions. The present study investigated the effect of PGE2 and agents known to increase intracellular cyclic adenosine monophosphate (cAMP) levels on 1) the induction of lymphokine-activated killer (LAK) cell activity from the peripheral blood lymphocytes (PBL) of both normal and glioma patients and on 2) the cytolytic activities of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). Cytolytic activity was measured against autologous and allogeneic tumor cells and the natural killer-resistant Daudi cell line. The results demonstrate that PGE2 and agents known to increase intracellular cAMP levels can significantly suppress the IL-2-dependent generation of cytolytic activity from the PBL of normal and glioma patients and from glioblastoma-derived TIL's. The inhibitory effects of these agents could not be reduced by higher concentrations of IL-2 or by cyclic guanosine monophosphate. Although the suppressive effect of PGE2 was most significant during the early stages of LAK cell generation, an inhibitory effect was still evident when PGE2 was added directly to the cytotoxicity assay. Secretion of PGE2 by glioblastoma cells in vivo may regulate both the generation of an immune response and the effectiveness of adoptively transferred immune cells.

Bucladesine↗

[Treatment using CDDP and radiation therapy in treating bladder tumor].

Combination therapy consisting of cis-diamine-dichloroplatinum (CDDP) and radiotherapy was used to treat bladder cancer. The subjects were 20 patients with bladder cancer we experienced since September, 1986. They were between 33 and 83 years old and consisted of 13 males and 7 females. Among the histotypes and grades, there were 3 cases of G2, 7 of G2-G3 and 10 of G3 metastatic epithelial carcinoma. The classification of primary tumors was T2 in six cases, T3a in 12 cases and T4 in two cases. In 12 cases where the bladder was preserved, this therapy was performed after TUR biopsy or TUR, and the effects were evaluated after observation periods of 5-17 months. Side effects caused by CDDP were anorexia in 15 cases, nausea and vomiting in 10 cases, leukopenia in 10 cases and thrombocytopenia in four cases. Those caused by the radiotherapy were diarrhea in seven cases and skin disorders in six cases. All of these side effects were mild and the patients recovered spontaneously.

Adult↗

Modification of lymphokine-activated killer cell accumulation into tumor sites by chemotherapy, local irradiation, or splenectomy.

The effects of chemotherapy or local irradiation on lymphokine-activated killer (LAK) cell accumulation into tumor sites were investigated. Lymphokine-activated killer cells labeled with 111In-oxine were injected into the caudal vein of C57BL/6 mice that had been previously transplanted with 3LL cancer. An adoptive transfer of LAK cells was carried out 4 days after treatments. Twenty-four hours after the transfer, tumor tissues were excised, and the accumulation of labeled LAK cells in the tumor was measured. In two different experiments, LAK cell accumulation in tumor in the nontreated group was 2.15% and 1.58% of the administered dose per gram of tissue. The accumulation in the groups of mice treated with cyclophosphamide, nimustine hydrochloride, or Adriamycin increased fourfold (7.38% dose/g, 6.61% dose/g), threefold (6.47% dose/g) and twofold (4.46% dose/g), respectively, as compared with the nontreated group. These agents induced significant tumor regression. In the group treated with bleomycin, which showed no significant effect on tumor growth, LAK cell accumulation in tumor remained unaltered (1.57% dose/g). However, the group treated with local irradiation, which induced significant tumor reduction, showed no increase in LAK cell accumulation into tumors. These results suggest that some antitumor drugs enhance LAK cell accumulation into tumor sites and that this increase is due to tumor modification by antitumor drugs.

Animals↗