Luiz F Pianowski

Kyolab laboratório de pesquisas farmacêuticas · Research

The identification of signaling pathways that are involved in gliomagenesis is crucial for targeted therapy design. In this study we assessed the biological and therapeutic effect of ingenol-3-dodecanoate (IngC) on glioma. IngC exhibited dose-time-dependent cytotoxic effects on large panel of glioma cell lines (adult, pediatric cancer cells, and pr...

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and...

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activit...

A large number of classic antineoplastic agents are derived from plants. Euphorbia tirucalli L. (Euphorbiaceae) is a subtropical and tropical plant, used in Brazilian folk medicine against many diseases, including cancer, yet little is known about its true anticancer properties. The present study evaluated the antitumor effect of the tetracyclic tr...

Fatigue is frequent among oncologic patients. Unpurified Paullinia cupana dry extract showed encouraging results for chemotherapy-induced fatigue in our previous studies. We report two randomized, double-blind studies with a standardized dry purified Paullinia cupana extract named PC-18. For both studies, we recruited early breast cancer patients w...

Background Some latency-reversing agents (LRAs) inhibit HIV-specific CD8+ T cell responses. In a prior study of protein kinase C (PKC) agonists, we found that bryostatin-1 inhibited elite controller/suppressor (ES) CD8+ T cell suppressive activity whereas prostratin had no effect. Ingenol-B is another PKC agonist with potent LRA activity both by it...

CD69 expression is upregulated following treatment with PKC-agonists. PBMCs from 6 CPs were treated with LRAs for 6 h, washed, then cultured for up to three days and examined for CD69 expression on CD8 + T cells. Mean expression ± standard error is indicated for each treatment at (A) 6 hours, (B) day 1, and (C) day 3. Symbols directly above treatme...

CD25 expression is not upregulated following treatment with LRAs. PBMCs from 6 CPs were treated with LRAs for 6 h, washed, then cultured for up to three days and examined for CD25 expression on CD8 + T cells. Mean expression ± standard error is indicated for each treatment at (A) 6 hours, (B) day 1, and (C) day 3. Symbols directly above treatments...

Ingenol-B/JQ1 combination causes slightly higher levels of % PD1 expression on CP CD8+ T cells. PBMCs from 6 CPs were isolated and treated with LRAs for 6 h, washed, then cultured for up to three days and examined for cell death as measured by percent annexin V expression. Mean expression ± standard error is indicated for each treatment at (A) 6 ho...

6Hours Data CPs. (XLSX)

Day1 Data CPs. (XLSX)

Ingenol-B does not induce proliferation of CD8+ T cells. (A) PBMCs were isolated from 6 HD PBMCs and CD4+ and CD8+ T cells enriched. Cells were combined at a 1:1 ratio and exposed to CellTrace CFSE. They were treated with LRAs for 6hrs incubated for an additional 3 days before examination for CD8+ T cell proliferation by percent CFSE expression. Me...

Day3 Suppression ES. (XLSX)

CD38 and HLA-DR co-expression is not upregulated following treatment with LRAs. PBMCs from 6 CPs were treated with LRAs for 6 h, washed, then cultured for up to three days and examined for CD38 and HLA-DR co-expression on CD8 + T cells. Mean expression ± standard error is indicated for each treatment at (A) 6 hours, (B) day 1, and (C) day 3. Symbol...

LRAs do not increase levels of cell death in CD8+ T cells following incubation with CD4+ T cells. PBMCs were isolated from 6 healthy donors and CD4+ and CD8+ T cells enriched. Cells were combined at a 1:1 ratio, co-cultured and treated with LRAs for 6hrs after which cells were extensively washed and incubated for an additional 3 days before examini...

6 Hours Data HDs. (XLSX)

Day1 Data HDs. (XLSX)

Day3 Data HDs. (XLSX)

Ingenol-B/JQ1 combination causes modest levels of cell death in CD8+ T cells. PBMCs from 6 CPs were isolated and treated with LRAs for 6 h, washed, then cultured for up to three days and examined for cell death as measured by percent annexin V expression. Mean expression ± standard error is indicated for each treatment at (A) 6 hours, (B) day 1, an...

Ingenol-B/JQ1 combination causes transient, slightly higher levels of % PD1 expression on HD CD8+ T cells. PBMCs from 8 HDs were treated with LRAs for 6 h before being washed and cultured for up to three days and examined for cell exhaustion as measured by percent PD1 expression. Mean expression ± standard error is indicated for each treatment at (...

Surface CD3 expression is downregulated following treatment with PKC-agonists. PBMCs from 6 CPs were isolated and treated with LRAs for 6 h, washed, then cultured for up to three days and examined for CD3 expression. Mean expression ± standard error is indicated for each treatment at (A) 6 hours, (B) day 1, and (C) day 3. Symbols directly above tre...

Day2 Data HDs. (XLSX)

Day3 Data CPs. (XLSX)

Day3 Proliferation HDs/CPs. (XLSX)

Objective: Resting CD4+ T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an SIV/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. Design: Pigtailed macaques were dual inoculated with SIVDel...

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi)...

Evidences suggest protein kinase C epsilon (PKCε) activation is involved in both inflammatory and neuropathic pains. We have previously shown that tetracyclic triterpene euphol produces antinociception in different models of persistent pain, an action associated with its anti-inflammatory properties. Among these properties, the cannabinoid system a...

The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known a...

HIV infection is not cleared by antiretroviral drugs due to the presence of latently infected cells that are not eliminated with current therapies and persist in the blood and organs of infected patients. New compounds to activate these latent reservoirs have been evaluated so that, along with HAART, they can be used to activate latent virus and el...

Although HAART effectively suppresses viral replication, it fails to eradicate latent viral reservoirs. The 'shock and kill' strategy involves the activation of HIV from latent reservoirs and targeting them for eradication. Our goal was to develop new approaches for activating HIV from latent reservoirs. We investigated capacity of Ingenol B (IngB)...

Purpose: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. Methods: We inclu...

e13559 Background: The latex from Euphorbia tirucalli is used in Brazil as anticancer and other disease as folk treatment; however, little is known about its anticancer proprieties. We report in vitro activity of 3 semi-synthetic ingenol compounds derived from E. tirucalli, ingenol A (ingenol-3-trans-cinnamate), ingenol B (3-caproyl-ingenol) and in...

e13557 Background: The tetracyclic triterpene alcohol euphol is the main constituent found in the sap of Euphorbia tirucalli. In Brazil its latex is used as anticancer and other diseaseas folk treatment, yet, little is known about its anticancer proprieties. We aimed to study the antitumor effect of euphol on a large panel of human cancer cell line...

e20680 Background: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. Methods: W...

Inflammation underlies the development and progression of a number of skin disorders including psoriasis, atopic dermatitis and cancer. Therefore, novel antiinflammatory agents are of great clinical interest for prevention and treatment of these conditions. Herein, we demonstrated the underlying molecular mechanisms of the antiinflammatory activity...

During the early stages of HIV infections, the virus establishes latency in a portion of the population of infected long-lived memory cells CD4+. Such latent viral reservoirs are inaccessible to standard antiretroviral drugs and result in an inability to eradicate the infection. A reactivation of the latent virus would offer an opportunity to expos...

e19552 Background: Paulinia cupana (guaraná) is an amazonic plant with stimulant proprieties which was shown previously to be effective for chemotherapy related fatigue in patients with breast cancer in a randomized double blind placebo controlled trial conducted by our group (J Altern Complement Med. 2011;17(6):505-12). Purpose: Extend our study t...

Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to hav...

The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and th...

e21002 Background: Paulinia cupana also known as Guarana is an amazonic plant which has been used for centuries as a tonic by indigenous populations. We have recently demonstrated that the dry crude extract of Guarana is effective in preventing the treatment of cancer related fatigue (CRF) in breast cancer patients undergoing adjuvant chemotherapy....

Trichilia catigua is a native plant of Brazil; its barks are used by some local pharmaceutical companies to prepare tonic drinks, such as Catuama. The present study was addressed to evaluate the effects of T. catigua hydroalcoholic extract in mouse nociception behavioral models, and to evaluate the possible mechanisms involved in its actions. Male...

This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (...

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the...

The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageena...