Ganetespib simultaneously deactivated multiple oncogenic pathways to potently reduce cell viability in TNBC cell lines, and suppressed lung metastases in experimental models. Ganetespib potentiated the cytotoxic activity of doxorubicin via enhanced DNA damage and mitotic arrest, conferring superior efficacy to the doxorubicin-cyclophosphamide regimen in TNBC xenografts. Ganetespib also promoted mitotic catastrophe and apoptosis in combination with taxanes in vitro, and these effects translated to significantly improved combinatorial activity in vivo. Marked tumor shrinkage of metastatic lung and lymphatic lesions were seen in patients on ganetespib monotherapy.
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CPA and GLV-1h68 have synergistic antitumor effects on PC14PE6-RFP xenografts. We strongly suppose that in the PC14PE6-RFP model the enhanced tumor growth inhibition achieved by combining GLV-1h68 with CPA is due to an effect on the vasculature rather than an immunosuppressive action of CPA. These results provide evidence to support further preclinical studies of combining GLV-1h68 and CPA in other highly angiogenic tumor models. Moreover, data presented here demonstrate that CPA can be combined successfully with GLV-1h68 based oncolytic virus therapy and therefore might be promising as combination therapy in human clinical trials.
Cyclophosphamide (CP) is a chemotherapy drug which causes deleterious effects on testicular tissue and increases free radicals in the body. The aim of this study is to investigate the protective effects of ethyl pyruvate (EP) on testicular improvement in CP treated animals.
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This case suggests that clinicians should pay more attention to the differential diagnosis between KD and POEMS syndrome. Gene analysis was helpful in detecting this rare confusing disease in this patient.
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This non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained.
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Choosing effective therapy for patients with malignant pheochromocytoma or paraganglioma (PPGL) is problematic and none of the options are curative. Although combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) is an established treatment option, only a limited number of case series have been reported in the literature. To determine the efficacy of CVD in patients treated at Tokyo Women's Medical University. Retrospective review of patients treated with CVD between 1989 and 2012 was conducted. Demographics, clinical presentation, imaging, and laboratory reports were reviewed and analyzed. Efficacy of CVD was ascertained from the biochemical and tumor responses. Twenty-three patients fulfilled study criteria and 6 of these were excluded due to inadequate follow-up or discontinuance by poor general condition or adverse effects. Thus, 17 cases were included in the study. The age and duration of the disease before initiation of CVD were 54.7 ± 12.0 years and 9.1 ± 8.1 years, respectively. The follow-up period after initiation of CVD ranged from 12 to 192 months (median, 60 months). Complete or partial biochemical and/or partial tumor response was achieved in 47.1 % (responders). No significant biochemical or tumor response was seen in 23.5 % and deterioration in biochemical and tumor outcomes was seen in 29.4 % (non-responders). No patient showed complete biochemical and tumor responses. In responders, these effects were documented within 4 months after initiation of CVD with a progression-free survival of 31 to 60 months (median, 40 months). Age at the first diagnosis with PPGL was younger (P < 0.05) and the lag time to eventual diagnosis of malignant disease was longer (P < 0.05) in responders than those in non-responders. The responders had improvements in hypertension and impaired glucose tolerance. Although CVD chemotherapy is not curative for patients with malignant PPGL, it does provide approximately half of the patients with biochemical, tumor, and hypertension benefits.
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IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T(reg)) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T(reg) cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.
In patients with atypical Crohn's disease features, including severe oral ulcerations and resistance to standard treatment, the possibility of a mature clonal CD8(+) T-cell lymphoproliferative disorder should be investigated. Clinicians should be aware of this differential diagnosis because CD8(+) T-cell lymphoma prognosis can be remarkably favorable upon oral treatment with cyclophosphamide.
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We observed rapid neutrophil engraftment on day +21 and for platelets on day +40. No early or late complications were recorded during 15 months follow-up. The patient developed only grade I skin GVHD. On day +30, chimerism assay showed 100% donor cells.
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This study demonstrated reduced likelihood of accepting CYC in African-American lupus patients compared with white lupus patients. This racial/ethnic variation was associated with belief in medication effectiveness and trust in the medical provider, suggesting that education about therapy and improved trust can influence decision-making among SLE patients.