L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells

Mendes, José Eduardo; Gonçalves, Ana Cristina; Alves, Raquel; Jorge, Joana; Pires, António; Ribeiro, Ana Isabel; Sarmento‐Ribeiro, Ana Bela

doi:10.1007/s12253-015-9998-4

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…To evaluate the immunological state of an individual, we used the blood collected in the field to make blood smears in the lab, followed by staining [ 44 ]. White blood cell counts and identification (100 cells per smears) were performed using a Nikon Eclipse Ni microscope (Nikon Instruments Europe B.V., Amsterdam, Netherlands).…”

Section: Methodsmentioning

confidence: 99%

Physiological Stress Reactions in Red Deer Induced by Hunting Activities

Vilela

Silva

Palme

et al. 2020

Animals

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Hunting activity is usually seen as a factor capable of causing an intense stress response in wildlife that may lead to short but also long-term stress. In the Lousã Mountain, Portugal, the population of red deer (Cervus elaphus) is the target of intensive seasonal hunting. We collected and measured cortisol (and its metabolites) in three tissues types (blood, feces and hair) from red deer hunted during two hunting seasons to evaluate the stress levels at different time windows. We also assessed the immunological and physical condition of the animals. We predicted that the hunting activity would act as a stressor inducing increased short and long-term stress levels in the population. Results showed an increase in hair cortisol levels during the months of harvesting. Surprisingly, the tendency for plasma cortisol levels was to decrease during the hunting season, which could be interpreted as habituation to hunting activity, or due to the hunting duration. Contrary to our predictions, fecal cortisol metabolites did not show any clear patterns across the months. Overall, our results suggest an influence of hunting activities on the physiological stress in red deer. In addition, hair seems to be useful to measure physiological stress, although more studies are required to fully understand its suitability as an indicator of long-term stress. Methodologically, our approach highlights the importance of simultaneously using different methods to assess short and long-term effects in studies on physiological stress reactions.

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Section: Methodsmentioning

confidence: 99%

Physiological Stress Reactions in Red Deer Induced by Hunting Activities

Vilela

Silva

Palme

et al. 2020

Animals

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“…A Ras/Raf pathway inhibitor, L744,832, induces cytotoxicity and cell death in DLBCL and Burkitt’s lymphoma cells. 38 It is possible that RASIP1 plays its lymphoma-promoting role by interacting with Ras. Meanwhile, RASIP1 has been demonstrated to bind to Rap1 15 , and regulate Cdc42 39 , suggesting that RASIP1 may function by regulating other molecules.…”

Section: Discussionmentioning

confidence: 99%

Ras interacting protein 1 facilitated proliferation and invasion of diffuse large B-cell lymphoma cells

Xing

Wang

Liu

et al. 2023

Cancer Biology & Therapy

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A GTPase binding protein, Ras interacting protein 1 (RASIP1), has been reported with a tumor-promoting role in lung cancer cells, and its role in lymphoma remains unknown. The analysis of medical databank shows that RASIP1 is upregulated in diffuse large B-cell lymphoma (DLBCL) specimens. In this article, we demonstrated that RASIP1 is highly expressed in DLBCL cell lines, compared with primary B cells. The gain- and loss-of-function experiments were performed to investigate the effects of RASIP1 on DLBCL cells. CCK-8, flow cytometry, western blot, and transwell assays demonstrated that silence of RASIP1 inhibited proliferation, cell cycle transition, and invasion and induced significant apoptosis in DLBCL cells, and ectopic expression of RASIP1 played opposite roles. Xenograft results revealed that RASIP1 facilitated the growth of DLBCL cells in vivo . These findings suggest that RASIP1 may be required for malignancy of DLBCL cells. In addition, we also found that the expression of RASIP1 was negatively regulated by forkhead box O3 (FOXO3), which has been reported to suppress the proliferation of DLBCL cells. Our results indicate that FOXO3 is bound to the promoter sequence of RASIP1 and inhibits its transcription. The suppressive effects of FOXO3 on proliferation and invasion of DLBCL cells were neutralized by RASIP1. In conclusion, we demonstrate that FOXO3 negatively regulated RASIP1 facilitates growth and invasion of DLBCL cells, provides novel diagnostic markers and therapeutic targets for DLBCL in clinic.

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“…To date, a limited number of studies are available on the efficacy and tolerance of EVL in the context of oncological diseases and pediatric LT, but there is adequate information available for adult patients. Animal and preclinical studies have shown anti-tumor effects of mTORi [21,22]. mTORi are already being used as a second-line treatment for renal cell carcinomas [14] as well as for advanced pancreatic neuroendocrine tumors [23] .…”

Section: Discussionmentioning

confidence: 99%

Malignancies and Pediatric Liver Transplantation: Promising Management with the mTOR-inhibitor Everolimus

Wehming¹,

Briem-Richter²,

Ganschow³

et al. 2021

OBM Transplantation

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Some malignancies such as hepatoblastoma may be an indication for liver transplantation (LT) or some, for example, post-transplant lymphoproliferative disease (PTLD) may develop after successful LT. An immunosuppressive therapy after LT can promote the recurrence of the primary malignancy. The mammalian target-of-rapamycin inhibitors (mTORi) are immunosuppressive agents with anti-tumor properties. We examined the impact of everolimus (EVL) together with calcineurin inhibitors on allograft outcome and patient survival in pediatric LT (PLT) with various tumors. This retrospective study included eleven liver-transplanted pediatric patients who received EVL after LT. The reason for adding an mTOR inhibitor was the neoplastic disease, either leading to LT (n = 7) or PTLD that developed after LT under immunosuppression (n = 3). The median age at the start of therapy was four years (range: seven months- 18 years); the median follow-up was 3 (range: 1 – 5) years). The primary endpoints were recurrence or metastasis of the primary tumor, uncontrolled PTLD, or death. Graft function and potential side effects were documented. Both patient survival and graft survival rates for the observation period were 100%. No patient developed recurrence or reported metastatic disease of the primary tumor. Liver function test results remained normal during the study period in 8 out of 11 patients. Three patients developed elevated liver enzymes that resolved over time. All the patients received EVL either as monotherapy (n = 2) or in combination with cyclosporine A (n = 7) or tacrolimus (n = 2). Typical side effects documented were recurrent infections (n = 8), stomatitis (n = 5), and cytopenia (n = 2), and medication was temporarily interrupted in one patient. Although the patient cohort was small, our results support the use of EVL in patients with tumor occurrence in the context of pediatric LT. No cases of recurrence or metastases were reported during the follow-up period after LT; sufficient immunosuppression was maintained. The side effect profile appeared acceptable. A longer follow-up in more number of patients is necessary to confirm these preliminary data.

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L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells

Cited by 11 publications

References 32 publications

Physiological Stress Reactions in Red Deer Induced by Hunting Activities

Physiological Stress Reactions in Red Deer Induced by Hunting Activities

Ras interacting protein 1 facilitated proliferation and invasion of diffuse large B-cell lymphoma cells

Malignancies and Pediatric Liver Transplantation: Promising Management with the mTOR-inhibitor Everolimus

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