Twenty patients with aplastic anemia underwent long-term administration (10 weeks) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses from 50 to 800 micrograms/m2 per day by intravenous infusion or 50 to 100 micrograms/m2 per day by subcutaneous injection and re-combinant human erythropoietin (rhEPO) in doses ranging from 2000 to 8000 IU/m2 per day by intravenous injection three times a week for at least 4 weeks. The goal was to evaluate whether therapy ameliorated pancytopenia in these patients as well as to determine its safety. All assessable patients showed a substantial increase in absolute neutrophil count, with a recovery of myeloid components (granulocyte series) in the bone marrow, after 2 to 10 weeks of treatment. An increase > 1.5 g/dL in hemoglobin (Hb) concentration was observed in 2 patients (10%). A decrease > 50% in red cell transfusion requirement was observed in 2 patients (10%). Seven patients showed recovery of neutropenia, anemia, and platelet count. In addition, there was no serious infection before or during therapy, and side effects were mild. Of the 20 patients, 3 showed a dramatic improvement in severe anemia after 10 weeks of treatment accompanying a recovery of erythroid components in the bone marrow. They no longer require red cell transfusions and have had normal Hb concentrations and normal ferrokinetics. These results indicate that long-term administration of rhG-CSF and rhEPO may benefit some patients with aplastic anemia. Further studies will be necessary to elucidate the mechanism by which rhGCSF and rhEPO stimulate hematopoiesis and improve hematologic abnormalities in these patients.

Adolescent↗

PubMedDate not supplied

Mastopathy-mimicking ultrasonographic appearance in a case with Burkitt's lymphoma.

We report a case of Burkitt's lymphoma, which was suspected to involve both breasts. US showed a replacement of the normal breast tissues by a diffusely mixed or mottled pattern of echo texture, associated by hypoechoic cyst-like masses with slight internal echogenicity. This pattern was indistinguishable from the sonographic changes produced by a mastopathy. These findings disappeared after successful chemotherapy for the Burkitt's lymphoma, suggesting that the ultrasonographic pattern of mastopathy was caused by the infiltration of the breast tissues by the lymphomatous cells.

Breast Neoplasms↗

PubMedDate not supplied

Modulation of multidrug resistance by cepharanthine in fresh human gastrointestinal tumor cells.

Resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance (MDR) gene. Cepharanthine (CEP) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we investigated the augmentation of DOX sensitivity by CEP using an MTT assay, and assessed the correlation between DOX sensitivity and P-glycoprotein expression by flow cytometry, in highly purified fresh human tumor cells obtained from 73 cancer patients. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by CEP in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of CEP on cytotoxicity and P-glycoprotein expression. Thus, CEP might be able to circumvent DOX resistance in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointestinal cancer cells.

BACKGROUND/AIMS: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. One of the major problems associated with cancer chemotherapy is drug-resistance of tumor cells, and resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein. We have tried to prove the correlation between P-glycoprotein expression and DOX-sensitivity in highly purified fresh human colorectal cancer and, moreover, to prove the differentiation of P-glycoprotein expression between the different kinds of cancers, including gastric cancer. METHODOLOGY: The present study was designed to quantify P-glycoprotein expression by flow cytometry, and DOX-sensitivity by MTT assay in highly purified fresh human tumor cells obtained from 29 cancer patients including 13 colorectal cancers and 16 gastric cancers. RESULTS: DOX-sensitivity decreased in proportion to P-glycoprotein expression in colorectal cancer. P-glycoprotein expression in colorectal cancer was higher than that in gastric cancer. Particularly, P-glycoprotein expression in colorectal cancer in the DOX low-sensitivity group was higher than in the DOX high-sensitivity group. CONCLUSIONS: The chemotherapeutic management of patients with colorectal cancer might be more effective if we can circumvent the effect of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Neutrophil functions and cytokine production in patients with gastric cancer.

BACKGROUND/AIMS: One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY: Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS: In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS: Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.

Aged↗

PubMedDate not supplied

In vitro antitumor effect of topoisomerase-I inhibitor, CPT-11, on freshly isolated human gastric and colorectal cancer.

CPT-11 is a comptothecin analogue which has shown a broad spectrum of strong antitumor effect against various cancers, including gastroenterological malignancies. In the present study, the antitumor effect of CPT-11 was determined by MTT assay for freshly isolated human gastric and colorectal cancer cells, especially highly purified tumor cells. Twenty-three patients with gastric cancer, and 32 patients with colorectal cancer were enrolled in this study. Three gastric and 3 colonic cancer cell lines were used to study the antitumor effect of CPT-11, and freshly isolated cancer cells from 3 patients with gastric cancer were investigated. The in vitro antitumor effect was tested by MTT assay, and showed % inhibition rate. CPT-11 and SN-38 showed the antitumor effect as a dose dependent matter for human gastric and colorectal tumor cells in vitro. From the results of chemosensitivity for freshly isolated gastric and colorectal tumor cells, antitumor effect of SN-38 was as strong as other conventional anticancer agents. It was demonstrated that the MTT assay was appropriate for the analysis of the antitumor effects of CPT-11 and SN-38, and that CPT-11 may be a worthwhile choice as an anticancer agent against gastric and colorectal cancer.

Antineoplastic Agents↗

PubMedDate not supplied

Elevation of serum alkaline phosphatase in clear cell chondrosarcoma of bone.

BACKGROUND: Clear cell chondrosarcoma is a rare bone tumor, which is sometimes misdiagnosed as a different bone neoplasm. MATERIALS AND METHODS: The files of 6 patients with clear cell chondrosarcomas were reviewed. Histological slides, radiographic studies, and pre- and post-operative serum alkaline phosphatase (ALP) levels were evaluated. Molecular and histochemical analyses of ALP were documented in one case of clear cell chondrosarcoma. RESULTS: Pre-operative serum ALP levels were elevated in 3 patients, and were normal in another 3 patients. After removal of the tumors, the enzyme levels decreased in all patients and returned to normal in 3 patients, who had pre-operative high ALP levels. Enzyme histochemical and molecular analyses demonstrated that the tumor produced ALP. CONCLUSION: Clear cell chondrosarcoma produces ALP, which can be used as a tumor marker in diagnosis and follow-up.

Adolescent↗

PubMedDate not supplied

Treatment of myxoid liposarcoma by marginal or intralesional resection combined with radiotherapy.

Local recurrence-free survival rate for myxoid liposarcoma (MLS) is related to negative surgical margins. The goal of surgery in the treatment of MLS is to obtain tumor-free surgical margins. When a tumor is adjacent to critical structures, wider resection, which can result in amputation, would be selected for local control. While recognizing that marginal or intralesional resection is associated with high risk of recurrence, circumstances occur that lead surgeons to conduct conservative surgery. To determine whether marginal or intralesional resection combined with radiotherapy can achieve local control, 10 cases (12 tumors) were reviewed involving MLS treated with marginal (8 tumors) or intralesional resection (4 tumors) followed by postoperative radiotherapy (50-70 Gy, average 59.2 Gy). No recurrences of MLS were observed locally at the mean follow-up of 58.1 months. The development of severe radiation-related complications was not detected. This medium follow-up study suggested that this method can achieve a high rate of local control.

Adult↗

PubMedDate not supplied

Non-T cell disturbance causes the suppression of the autologous mixed lymphocyte reaction in patients with gastric carcinoma.

We investigated the accessory function of non-T cells to autoreactive T cells in autologous mixed lymphocyte reaction (AMLR) and clarified the cause of the suppression of autoreactivity in patients with gastric carcinoma. The response of T cells in the AMLR in gastric cancer patients was significantly suppressed compared with that in controls. In patients in whom the AMLR of the spleen was suppressed more than that of the peripheral blood, the degree of stimulation of non-T cells from the spleen was remarkably suppressed, on the other hand, in patients in whom AMLR of the peripheral blood was suppressed more than the spleen, the degree of stimulation from the peripheral blood was remarkably suppressed. The expression of HLA-DR antigens on non-T cells of gastric cancer patients was lower than that of controls. AMLR was considerably decreased in controls by the treatment non-T cells with anti-HLA-DR MoAb, but not in cancer patients. Treatment of non-T cells from the spleen of gastric cancer patients with IFN-gamma remarkably improved T cell proliferation in the AMLR. IFN-gamma also enhanced the expression of HLA-DR antigens on non-T cells. The disturbance of non-T cells was not biased to a specific population. These disturbances of non-T cells suppressed the AMLR independently of stage status. Therefore, the immunological abnormality of non-T cells manifested by reduced accessory function to autoreactive T cells may cause impaired immunological surveillance against tumors and permit cancer cell growth.

Antibodies, Monoclonal↗

PubMedDate not supplied

Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro.

We have investigated whether or not polysaccharide preparation PSK directly augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes (TILs). TILs were separated from 10 patients with gastrointestinal cancer (5 gastric cancers, 3 colon cancers and 2 pancreatic cancers). TILs were cultured with IL-2 and PSK for 7 days. The DNA synthesis of TILs was augmented by incubation with 100 micrograms/ml of PSK, which was similar to serum level with oral administration of PSK in cancer patients. The effect of PSK in DNA synthesis was also found by elimination of non-T cells. Furthermore, we established TIL clones and examined the effect of PSK on TILs clones. The DNA synthesis was augmented by PSK in CD4 positive and CD8 positive TIL clones without non-T cells, suggesting that PSK acts directly on TILs. We examined the cytotoxic activities of TILs by the 4-h and 16-h 51Cr release assay. PSK did not affect the cytotoxic activity of TILs against autologous tumor cells and KATO-III cells in the 4h 51Cr release assay, whereas PSK induced high lysability of TILs against autologous tumor cells in the 16-h 51Cr release assay. We studied the ability of PSK to induce cytokines from TILs using a double chamber plate. The DNA synthesis of tumor cells was more suppressed by the mixed-tumor cell culture supernatants of TILs cultured with PSK, compared to that of TILs cultured without PSK. It is suggesting that PSK induced long term killing activity of TILs by induction of cytotoxic cytokines. Thus, PSK augmented the proliferative response of TILs without interaction of T cells and non-T cells and induced cytotoxic cytokines of TILs.

Cell Division↗

PubMedDate not supplied

In vitro augmentation of cytotoxic activity of peripheral blood lymphocytes and spleen cells of cancer patients by ubenimex.

Ubenimex is used for the immunotherapy of malignant diseases as a biological response modifier (BRM) and shows beneficial effects as an adjuvant treatment. In the present study, the in vitro effects of ubenimex on the cytotoxic activity of peripheral blood lymphocytes (PBL) and spleen cells of cancer patients and the mechanism of killer cell activation were investigated. Cytotoxic activity against K562, KATO-III and autologous tumor cells was augmented by in vitro sensitization with ubenimex (p < 0.05). The optimal concentration of ubenimex for induction of cytotoxic activity was 1 micrograms/ml, similar to serum levels after clinical oral administration. The major population of killer cells activated by ubenimex recognizing K562 was CD16+, and those recognizing KATO-III were mainly CDA+ or CD8(5) cels and CD16+ NK cells, while CDA5 or CD8+T cells comprised the majority of killer cells which showed autologous tumor-killing activity. Augmentation of the cytotoxic activity of mononuclear cells by ubenimex was blocked by both anti-IL-1 beta Ab and anti-IL-2 AB. However, the expression of IL-2 receptor (p55, p75) on effector cells was not altered. Ubenimex augmented not only NK activity but also autologous tumor killing activity of PBL and spleen cells via macrophage activation. These activities of ubenimex may be clinically beneficial as an adjuvant treatment.

Adjuvants, Immunologic↗

PubMedDate not supplied

Ubenimex treatment enhances the susceptibility of gastric cancer cell lines to lymphokine-activated killer cells.

We investigated the direct effects of ubenimex on the modification of gastric carcinoma cell lines' susceptibility to killer cells, and the mechanism of its action. The susceptibility of both MKN-45 cells and KATO-III cells to LAK cells was enhanced by treatment with ubenimex for 48 h (p < 0.05), and the optimal concentration for this effect was 10 micrograms/ml. The susceptibility of ubenimex treated KATO-III cells to CD3+ LAK cells, especially to those also expressing CD8, was enhanced. DNA synthesis of tumor cells was not impaired by treatment with ubenimex at all concentrations tested. The binding rate of LAK cells and ubenimex-treated KATO-III cells was similar to that between LAK cells and untreated KATO-III cells. Moreover, no alterations in the expression of any antigen related to mononuclear cell-binding to tumor cells were induced by ubenimex. Lysis or the inhibition of DNA synthesis of tumor cells by LAK cell supernatant was enhanced by ubenimex. These results suggested that the mechanism responsible for the augmentation of tumor cell susceptibility by ubenimex may be a result of the alteration of their sensitivity to some Iytic factors released by LAK cells. Thus ubenimex shows not only an indirect host-mediated anti-tumor activity but also a direct effect on tumor cells, modifying their susceptibility to killer cells, and this may explain why ubenimex shows beneficial clinical effects as an adjuvant treatment.

Adjuvants, Immunologic↗