Malignant peripheral primitive neuroectodermal tumor of the uterus

Peripheral primitive neuroectodermal tumor (PPNET) is rare, occurring most often in young adults. Approximately 50 cases have been reported, with only four cases involving the female genital tract. We report the fifth patient. The term "PPNET" should be used only for tumors with neuroectodermal elements exclusively that occur at sites outside the central and sympathetic nervous system. The pathologic differential diagnoses include rhabdomyosarcoma, immature malignant teratoma, small cell carcinoma of the cervix, and ganglioneuroma. Therapy for this tumor has varied, and no effective regimen has been established.     

化疗药物靶向肿瘤相关免疫抑制性细胞的研究进展

肿瘤相关免疫抑制性细胞在肿瘤的发生、发展过程中发挥重要的免疫抑制作用,肿瘤的发展和转移常伴有这些细胞的异常聚集。调节性T细胞(regulatory T cells,Treg)和髓系来源的抑制性细胞(myeloid-derived suppressor cells,MDSC)是免疫抑制性细胞网络的主要成分,它们通过直接或间接作用负向调节其他免疫细胞,抑制抗肿瘤的免疫反应。最新研究显示,有些常规化疗药物除可直接杀伤肿瘤细胞外,还可降低Treg和MDSC的数量,抑制其功能,从而增强抗肿瘤免疫功能。因此,将化疗药物作为预处理方案,凭借其免疫调节作用联合后续的过继性细胞免疫治疗可有效增强抗肿瘤免疫应答。化学免疫治疗策略将改变人们对传统化疗抗肿瘤地位的认识,继而更加合理地应用化疗药物。     

An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy

We describe three cases of relapsed hairy cell leukaemia (HCL) treated with pentostatin plus rituximab. All three achieved bone marrow complete remission but had persistent splenomegaly and hypersplenism. Because of the clinical uncertainty of its significance, they were all splenectomized. The spleen histology showed no evidence of HCL, but a five‐fold thickening of the splenic capsule and areas of fibrosis in the red pulp. This process may have contributed to the lack of elasticity and caused the persistent splenomegaly. We discuss the clinical implications for future patient management. The three patients remain in remission at 1 + , 5 +  and 9 +  years.     

Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia

BACKGROUND: The prevalence of chronic lymphocytic leukemia (CLL) increases with age. Although chemoimmunotherapy (CIT) has dramatically improved response rates in patients with CLL, some CIT regimens are not well tolerated by many patients >or=70 years of age. METHODS: Sixty-four previously untreated patients with CLL and serum creatinine <1.5 times the upper limit of normal who met National Cancer Institute (NCI) 96-WG criteria for treatment received pentostatin (2 mg/m(2)), cyclophosphamide (600 mg/m(2)), and rituximab (375 mg/m(2)). The authors measured performance status at study entry and used age, weight, and baseline creatinine to calculate creatinine clearance (CrCl). RESULTS: Eighteen of 64 (28%) patients were ages >or=70 years. Although individuals ages >or=70 years were more likely to have delayed treatment cycles (28% vs 7%; P=.03), there were no significant differences in the number of cycles administered, need for dose reductions, or grade 3-4 hematologic, infectious, or other toxicities. No significant differences in overall response rate, complete response rate, or progression-free survival were observed by age. Twenty-five (39%) patients had a CrCl < 70 mL/min (range, 34-67). Although individuals with CrCl < 70 were more likely to require dose reduction (24% vs 5%; P=.05), there were no significant differences in the number of cycles administered or grade 3-4 hematologic, infectious, or other toxicities. No significant difference in overall response rate, complete response rate, or progression-free survival were observed between patients with CrCl >or= 70 mL/min and those with CrCl < 70 mL/min. CONCLUSIONS: In this clinical trial, the PCR regimen was well tolerated by older patients and individuals with CrCl 相似文献   

Combined effect of fluconazole and thymosin alpha 1 on systemic candidiasis in mice immunosuppressed by morphine treatments.

Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin alpha 1 (T alpha 1)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 10(6) C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and T alpha 1 prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with T alpha 1 or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of T alpha 1 and fluconazole is due to a direct antifungal action and activation of the immunocompetence.     

Chemoimmunotherapy of a murine fibrosarcoma: Critical factors for success of combined modality therapy

Thiabendazole (TBZ), a new nonspecific immunopotentiator, was evaluated in combination with Cytoxan in the therapy of a syngeneic murine fibrosarcoma. The reduction of tumor burden by chemotherapy was critical in achieving an optimal response from immunotherapy. Eighty-eight percent of the mice that responded to Cytoxan had sustained regression of tumor with TBZ treatment. The response to TBZ was markedly diminished, both in duration and magnitude, in the mice considered to be Cytoxan nonresponders. Timing of immunotherapy was also important. If Cytoxan and TBZ were given simultaneously, growth kinetics similar to those observed with Cytoxan alone were observed. However, if TBZ was given 4 days after Cytoxan administration, prolonged regression of tumor was seen. Alone, TBZ was most effective at a dose of 20 mg/kg. However, in combination with Cytoxan the most effective dose was 0.2 mg/kg. The implications of this finding are discussed.     

Mechanisms of levamisole-induced granulocytopenia in breast cancer patients

Five of 39 (13%) women treated with adjuvant combination chemotherapy plus levamisole immunotherapy after mastectomy for Stage II or III breast cancer developed levamisole-induced granulocytopenia. This complication occurred in each of the women between six and ten weeks after the completion of six months of combination chemoimmunotherapy when they were taking levamisole alone. Although none of the patients had an HLA B-27 locus and leukoagglutinins could not be demonstrated, complement-dependent, IgM mediated, peripheral destruction of granulocytes was documented using a microgranulocytotoxicity assay. In addition, a factor(s) present in serum from patients developing levamisole-induced granulocytopenia caused suppression of bone marrow granulocyte progenitor cells (CFU-C). The possible relationships between levamisole-induced peripheral granulocyte destruction and bone marrow CFU-C suppression are discussed.