Roberto Gil

Icahn School of Medicine at Mount Sinai

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Mariana Gil

Hospital Regional de Alta Especialidad del Bajío

Gabriel Prolla

Centro de Pesquisas Oncológicas

N.R. Farnsworth

University of Illinois Chicago

Bernardo Garicochea

Centro de Pesquisas Oncológicas

John M. Pezzuto

Baystate Health

Thawatchai Santisuk

Royal Forest Department

Alexandre A. Jácome

Centro de Pesquisas Oncológicas

Luiza Labrunie

Rinaldo Gonçalves

Instituto Nacional do Câncer

Melanie J. O’Neill

Columbia University

Cooperative Institutions

University of Illinois Chicago

Icahn School of Medicine at Mount Sinai

Centro de Pesquisas Oncológicas

Fleury S.A. (Brazil)

Universidade de São Paulo

Mahidol University

Illinois College

GlaxoSmithKline (United Kingdom)

Wellcome Trust

Sociedade Brasileira de Oncologia Clínica

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Capítulo 9 - Câncer de cólon localizado

Mariana Vargas Gil Roberto Gil Gabriel Prolla

Uma pequena parcela dos pacientes com câncer colorretal (CCR) metastático pode ser curada com ressecção da doença metastática, especialmente pacientes com doença de pouco volume hepático e/ou pulmonar.

10.56271/978-85-8400-180-4-cap9

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The diabetic microenvironment causes mitochondrial oxidative stress in glomerular endothelial cells and pathological crosstalk with podocytes

Cell Communication and Signaling (2020)

Gabriella Casalena Liping Yu Roberto Gil Samuel Rodriguez Shantel Sosa

Abstract Background In the setting of diabetes mellitus, mitochondrial dysfunction and oxidative stress are important pathogenic mechanisms causing end organ damage, including diabetic kidney disease (DKD), but mechanistic understanding at a cellular level remains obscure. In mouse models of DKD, glomerular endothelial cell (GEC) dysfunction precedes albuminuria and contributes to neighboring podocyte dysfunction, implicating GECs in breakdown of the glomerular filtration barrier. In the following studies we wished to explore the cellular mechanisms by which GECs become dysfunctional in the diabetic milieu, and the impact to neighboring podocytes. Methods Mouse GECs were exposed to high glucose media (HG) or 2.5% v/v serum from diabetic mice or serum from non-diabetic controls, and evaluated for mitochondrial function (oxygen consumption), structure (electron microscopy), morphology (mitotracker), mitochondrial superoxide (mitoSOX), as well as accumulation of oxidized products (DNA lesion frequency (8-oxoG, endo-G), double strand breaks (γ-H2AX), endothelial function (NOS activity), autophagy (LC3) and apoptotic cell death (Annexin/PI; caspase 3). Supernatant transfer experiments from GECs to podocytes were performed to establish the effects on podocyte survival and transwell experiments were performed to determine the effects in co-culture. Results Diabetic serum specifically causes mitochondrial dysfunction and mitochondrial superoxide release in GECs. There is a rapid oxidation of mitochondrial DNA and loss of mitochondrial biogenesis without cell death. Many of these effects are blocked by mitoTEMPO a selective mitochondrial anti-oxidant. Secreted factors from dysfunctional GECs were sufficient to cause podocyte apoptosis in supernatant transfer experiments, or in co-culture but this did not occur when GECs had been previously treated with mitoTEMPO. Conclusion Dissecting the impact of the diabetic environment on individual cell-types from the kidney glomerulus indicates that GECs become dysfunctional and pathological to neighboring podocytes by increased levels of mitochondrial superoxide in GEC. These studies indicate that GEC-signaling to podocytes contributes to the loss of the glomerular filtration barrier in DKD. Graphical abstract

Endothelial Dysfunction

10.1186/s12964-020-00605-x

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Later lines of systemic therapy in patients with metastatic colorectal cancer: real-world data from a setting with barriers to access cancer therapies

Journal of Gastrointestinal Oncology (2024)

Alexandre A. Jácome Maria Cecília Mathias-Machado Mariana Gil Thaís de Melo Passarini Stefano Cristofaro

Regorafenib and trifluridine/tipiracil (TFD/TPI) are oral systemic therapies with survival benefit in chemorefractory metastatic colorectal cancer (mCRC) patients, but they are not widely available worldwide. We aimed to evaluate the treatment patterns and outcomes of patients with limited access to these drugs. Retrospective study involving 510 patients with mCRC who were treated at five different centers in Brazil, from January 2011 to December 2019. We analyzed the characteristics and clinical outcomes of patients who were exposed to third-line and beyond systemic therapy (N=148). A total of 148 (29%) and 73 (14%) patients received third- and fourth-line therapies, respectively. Most patients had left-sided tumors (80%) and had undergone primary tumor resection (87%) and metastasectomy (62%). From the initiation of third-line therapy, median follow-up was 17.8 months and median overall survival (OS) was 13.1 months (95% confidence interval: 8.1-18.0) (58% of deaths). The most adopted therapies were reexposure to previous chemotherapy regimens (85% third-line and 71% fourth-line), followed by regorafenib (13% and 25%) and TFD/TPI (2% and 4%). In multivariable analysis, male patients and right-sided tumors were significant unfavorable prognostic factors for OS. In a real-world setting with barriers to accessing the standard of care of chemorefractory mCRC, reexposure to chemotherapy was the main therapeutic strategy, with potential negative influence on OS. Our study highlights how barriers hamper the achievement of health equity in cancer care and increases the awareness of patients and stakeholders, contributing to engaging them in ensuring equitable access to high-quality cancer care.

Systemic therapy

10.21037/jgo-24-524

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ChemInform Abstract: Novel Cytotoxic Ring‐A seco‐Cycloartane Triterpenes from Gardenia coronaria and G. sootepensis.

ChemInform (1997)

Gloria L. Silva Roberto Gil Bao‐Dong Cui H Chai Thawatchai Santisuk

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Terpene

Gardenia

10.1002/chin.199718226

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Colangiocarcinoma

Rinaldo Gonçalves Jéssica Andrade de Albuquerque Luiza Labrunie João Folgaci Jairo Fernandes Frutuoso

O colangiocarcinoma (CC) é uma doença maligna rara, compreendendo um grupo de tumores com características patológicas de diferenciação biliar, podendo ter localização intra ou extra-hepática. A apresentação intra-hepática (CCih) corresponde a 10%-20% de todos os tumores hepáticos primários, sendo o segundo tumor primário mais frequente do fígado depois do hepatocarcinoma.

10.56271/978.65.87679.50.1-13

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