Dysgerminoma in a patient with a tumor of the neck. Empiric treatment of stage IV dysgerminoma

The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient's fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.     

Familial association of basilar bifurcation aneurysm and moyamoya disease--four case reports

Four patients presented with familial intracranial aneurysms and familial moyamoya disease, including one patient with both familial intracranial aneurysm and moyamoya disease. Basilar bifurcation aneurysms were present in two patients, moyamoya disease in one, and both basilar bifurcation aneurysm and moyamoya disease in one. These events are most likely to arise from different genetic abnormalities associated with basilar bifurcation aneurysm and moyamoya disease.     

Angiosarcoma of the spleen 11 years after chemotherapy for testicular seminoma: a case report

A 32-year-old man who had previously undergone chemotherapy for testicular seminoma 11 years ago was admitted to our hospital with a pain in the right leg. Computed tomography (CT) and bone scintigraphy revealed splenomegaly and multiple bone disease. Laboratory examination showed thrombocytopenia. The pathologic diagnosis of the resected spleen and the biopsied rib was angiosarcoma. We found no reports of angiosarcoma following previous chemotherapy for testicular cancer. It is unclear whether the angiosarcoma is a secondary neoplasm induced by the chemotherapy or not. However, the patient had a chromosomal aberration of the peripheral lymphocytes. The chemotherapy might also have affected the chromosomal aberration presumably in endothelial progenitor cells causing the development of a secondary neoplasm. To our knowledge, this is the first case of angiosarcoma after chemotherapy for testicular seminoma.     

Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has recently been described as a distinct clinicopathological entity among idiopathic interstitial pneumonias (IIP), having more favorable prognosis than usual interstitial pneumonia (UIP). Although NSIP was initially reported to also occur in patients with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), the prevalence of NSIP and its prognostic significance in IP-CVD remains to be determined. Thus, we attempted to clarify clinical characteristics and prognostic significance of NSIP in IP-CVD. METHODS: We histologically examined surgical lung biopsies from 43 patients with IP-CVD based on a current classification of interstitial pneumonias, and compared the clinical characteristics and prognostic significance of NSIP with UIP in IP-CVD. We also studied 98 patients with biopsy-proven NSIP and UIP in IIP, and compared the prognostic significance of histopathologic subclassification in IIP with that in IP-CVD. RESULTS: In IP-CVD, twenty-six patients (60%) were classified as NSIP, 17 (40%) as UIP. In contrast, 76 (77%) were categorized into UIP and 22 (23%) into NSIP of the patients with IIP. No significant difference in survival rates was observed between UIP and NSIP in IP-CVD (p = 0.3863), while, in IIP, NSIP has a significant better survival than UIP (p = 0.022). CONCLUSIONS: These results suggest that NSIP is more common histologic pattern than UIP in IP-CVD and, unlike in IIP, the prognosis of NSIP patients may not be different from that of UIP patients in IP-CVD.     

A novel carbazole topoisomerase II poison,ER-37328: potent tumoricidal activity against human solid tumors in vitro and in vivo

We have discovered a novel topoisomerase II (topo II) poison, ER-37328 (12,13-dihydro-5-[2-(dimethylamino)ethyl]-4H-benzo[c]py-rimido[5,6,1- jk ]carbazole-4,6,10(5H, 11H)-trione hydrochloride), which shows potent tumor regression activity against Colon 38 cancer inoculated s.c. Here, we describe studies on the cell-killing activity against a panel of human cancer cell lines and the antitumor activity of ER-37328 against human tumor xenografts. In a cell-killing assay involving 1-h drug treatment, ER-37328 showed more potent cell-killing activity (50% lethal concentrations (LC₅₀s) ranging from 2.9 to 20 μM ) than etoposide (LC₅₀s>60 μM ) against a panel of human cancer cell lines. ER-37328 induced double-stranded DNA cleavage, an indicator of topo II-DNA cleavable complex formation, within 1 h in MX-1 cells, and the extent of cleavage showed a bell-shaped relationship to drug concentration, with the maximum at 2.5 μM . After removal of the drug (2.5 μM ) at 1 h, incubation was continued in drug-free medium, and the amount of cleaved DNA decreased. However, at 10 μM , which is close to the LC₅₀ against MX-1 cells, DNA cleavage was not detected immediately after 1-h treatment, but appeared and increased after drug removal. This result may explain the potent cell-killing activity of ER37328 in the 1-h treatment. In vivo , ER-37328 showed potent tumor regression activity against MX-1 and NS-3 tumors. Moreover, ER-37328 had a different antitumor spectrum from irinotecan or cisplatin against human tumor xenografts. In conclusion, ER-37328 is a promising topo II poison with strong cell killing activity in vitro and tumor regression activity in vivo , and is a candidate for the clinical treatment of malignant solid tumors. (Cancer Sci 2003; 94: 119–124)     

Membrane transport and antitumor activity of pirarubicin, and comparison with those of doxorubicin.

We have compared the membrane transport and antitumor activity of pirarubicin with those of doxorubicin in M5076 ovarian sarcoma, which exhibits low sensitivity to doxorubicin. Pirarubicin was rapidly taken up by M5076 cells and the intracellular concentration of pirarubicin reached more than 2.5-fold that of doxorubicin. In terms of the 50% cell growth-inhibitory concentration in vitro, pirarubicin was more effective than doxorubicin. Thus, the intracellular concentration influenced the cytotoxicity of these anthracycline agents. On comparison of the nuclear uptake of pirarubicin and doxorubicin, the nucleus/cell ratio of pirarubicin was found to be about 40%, whereas that of doxorubicin reached more than 80%. As the intranuclear concentration of pirarubicin is dependent on nuclear transport, the increases in not only cell membrane transport, but also nuclear membrane transport contributed to the enhancement of the efficacy of pirarubicin. In M5076 solid tumor-bearing mice, pirarubicin reduced the tumor weight to 60% of the control level, although doxorubicin had no effect. These results were supported by the intracellular uptake of pirarubicin. Moreover, theanine, which inhibited the pirarubicin efflux from M5076 cells, increased by 1.3-fold the pirarubicin concentration in the tumor and enhanced the therapeutic efficacy of pirarubicin 1.7-fold. In conclusion, our results suggest that an increase in the concentration of an anthracycline derivative in tumor cells due to alteration of cell membrane transport results in enhancement of the antitumor activity.     

Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.     

In vivo Cisplatin Resistance Depending upon Canalicular Multispecific Organic Anion Transporter (cMOAT)

The in vitro sensitivities to cisplatin of AH66 and AH66F cells, a variant obtained from AH66 cells, were very similar, when assayed in a medium containing 5% fetal bovine serum (FBS), whereas in the in vivo experiments AH66F cells were sensitive and AH66 cells were highly resistant to cisplatin. In this study, we examined the mechanism of the in vivo cisplatin resistance of AH66 cells. The in vitro cisplatin sensitivity of AH66 cells was lowered by changing FBS to 5% ascites fluid (ASF) in the assay medium and the sensitivity in FBS by treatment with buthioninesulfoximine (BSO). The sensitivity of AH66F cells was not changed by these treatments. Moreover, after culture in 5% ASF for 48 h, the accumulation of cisplatin in AH66 cells was decreased and the efflux of cisplatin from the cells was accelerated. The accumulation of cisplatin in AH66 cells in ASF was increased by pretreatment with BSO, sodium azide or probenecid. Then, we examined the expression of the glutathione (GSH) conjugate efflux pump family. Among them, only the expression of canalicular multispecific organic anion transporter (cMOAT) in AH66 cells was decreased by culture in FBS and enhanced by ASF. These results suggest that some substances contained in ASF enhanced the expression of cMOAT in the plasma membrane of AH66 cells and this transporter actively extruded cisplatin-GSH conjugate from the cells. Consequently, AH66 cells afford a cisplatin-resistant tumor in the host.     

Experimental study on intraoperative autotransfusion during urological operation]

The value of autotransfusion is widely recognized in the surgical community and may be of increasing importance in prevention of acquired immunodeficiency syndrome and hepatitis. The concern of possible contamination of the blood with urine, bacteria in urine or viable tumor cells has limited the wide use of intraoperative autotransfusion (IAT) in urological operation. There have been no experimental reports about protection of the blood from such contamination. To investigate separation of the blood from a contaminated mixture by using an autotransfusion machine, Haemonetic Cell Saver, a study composed of three experiments was performed. First, 200 ml of blood was mixed 200 ml of urine, and thereafter, the mixture was processed by the machine and the concentration erythrocytes were collected in a bag. Biochemical analysis of the collected erythrocyte solution (CES) was performed. Second, 200 ml of blood was mixed with 200 ml of urine that was adjusted to contain each 10(7)/ml of four bacterial strains. The bacteriological study of the CES was performed. Third, 200 ml of blood was mixed with 200 ml of urine that was adjusted to contain 10(7) cancer cells. Two cell lines, KK47 originated from human bladder cancer and ACHN originated from human renal cell carcinoma was used. The cytological study of the CES was performed. The results of these experiments were: Urine constituents were completely removed from the mixture. However, all strains of bacteria could not be separated, although the number of bacteria decreased. Cancer cells were found in the CES. In conclusion IAT should be done at urological operation in selected patients that have sterile urine and do not have tumor cells in the operation field.