Efficacy of oral metformin in a patient with metastatic adrenocortical carcinoma: Examination of mechanisms and therapeutic implications

Rd, Peixoto; Lm, Gomes; Tt, Sousa; Dj, Racy; Shigenaga, Mark K.; Ra, Nagourney

doi:10.1177/2036361317749645

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…We cannot attribute these higher figures during the first wave to the severity of the disease alone but also to the initial lack of knowledge in the management of COVID-19 by clinical staff. Other studies showed a higher percentage of ICU admission (17% and 26%) [3,49,50] with a similar median stay of 14 days. Of those patients in our study admitted to the ICU, 6.5% needed orotracheal intubation with the highest rate also in the 1st wave (10.7% vs. 5.1% 2nd wave, p < 0.05; and 3.5% 3rd wave, p < 0.01).…”

Section: Discussionmentioning

confidence: 62%

A Comparative Study between the Three Waves of the Pandemic on the Prevalence of Oropharyngeal Dysphagia and Malnutrition among Hospitalized Patients with COVID-19

et al. 2022

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Background: The phenotype of patients affected by COVID-19 disease changed between the waves of the pandemic. We assessed the prevalence of oropharyngeal dysphagia (OD), malnutrition (MN), and mortality between the first three waves of COVID-19 patients in a general hospital. Methods: a prospective observational study between April 2020–May 2021. Clinical assessment for OD was made with the volume-viscosity swallowing test; nutritional assessment was performed consistent with GLIM criteria. A multimodal intervention was implemented in the second and third wave, including (a) texturized diets—fork mashable (1900 kcal + 90 g protein) or pureed (1700 kcal + 75 g protein), (b) oral nutritional supplements (500–600 kcal + 25–30 g protein), and (c) fluid thickening (250 mPa·s or 800 mPa·s). Results: We included 205 patients (69.3 ± 17.6 years) in the 1st, 200 (66.4 ± 17.5 years) in the 2nd, and 200 (72.0 ± 16.3 years;) in the 3rd wave (p = 0.004). On admission, prevalence of OD was 51.7%, 31.3% and 35.1%, and MN, 45.9%, 36.8% and 34.7%, respectively; mortality was 10.7%, 13.6% and 19.1%. OD was independently associated with age, delirium, and MN; MN, with age, OD, diarrhea and ICU admission; mortality, with age, OD and MN. (4) Conclusions: Prevalence of OD, MN and mortality was very high among COVID-19 patients. OD was independently associated with MN and mortality. An early and proactive multimodal nutritional intervention improved patients’ nutritional status.

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Section: Discussionmentioning

confidence: 62%

A Comparative Study between the Three Waves of the Pandemic on the Prevalence of Oropharyngeal Dysphagia and Malnutrition among Hospitalized Patients with COVID-19

et al. 2022

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“…The patient was treated with mitotane in combination with other chemotherapeutic drugs, which resulted in stable disease. This was followed by metformin treatment (500 mg/twice a day) in combination with mitotane, which resulted in the further reduction of the nodule size, with a continued response to this combination therapy for nine months (Peixoto et al 2018).…”

Section: Tumors Of the Adrenal Cortex: Adrenocortical Adenoma/adrenocmentioning

confidence: 99%

The role of an anti-diabetic drug metformin in the treatment of endocrine tumors

Thakur

Daley

Kłubo-Gwieździńska

2019

Journal of Molecular Endocrinology

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Incidence of endocrine cancers is rising every year. Over the last decade, evidence has accumulated that demonstrates the anti-cancer effects of an anti-diabetic drug, metformin, in endocrine malignancies. We performed a literature review utilizing the PubMed, Medline and clinicaltrials.gov databases using the keyword ‘metformin’ plus the following terms: ‘thyroid cancer’, ‘thyroid nodules’, ‘parathyroid’, ‘hyperparathyroidism’, ‘adrenal adenoma’, ‘Cushing syndrome’, ‘hyperaldosteronism’, ‘adrenocortical cancer’, ‘neuroendocrine tumor (NET)’, ‘pancreatic NET (pNET)’, ‘carcinoid’, ‘pituitary adenoma’, ‘pituitary neuroendocrine tumor (PitNET)’, ‘prolactinoma’, ‘pheochromocytoma/paraganglioma’. We found 37 studies describing the preclinical and clinical role of metformin in endocrine tumors. The available epidemiological data show an association between exposure of metformin and lower incidence of thyroid cancer and pNETs in diabetic patients. Metformin treatment has been associated with better response to cancer therapy in thyroid cancer and pNETs. Preclinical evidence suggests that the primary direct mechanisms of metformin action include inhibition of mitochondrial oxidative phosphorylation via inhibition of both mitochondrial complex I and mitochondrial glycerophosphate dehydrogenase, leading to metabolic stress. Decreased ATP production leads to an activation of a cellular energy sensor, AMPK, and subsequent downregulation of mTOR signaling pathway, which is associated with decreased cellular proliferation. We also describe several AMPK-independent mechanisms of metformin action, as well as the indirect mechanisms targeting insulin resistance. Overall, repositioning of metformin has emerged as a promising strategy for adjuvant therapy of endocrine tumors. The mechanisms of synergy between metformin and other anti-cancer agents need to be elucidated further to guide well-designed prospective trials on combination therapies in endocrine malignancies.

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“…Adrenocortical carcinoma (ACC) is another of the index cancers associated with LFS. An adult patient with LFS and metastatic ACC, a disease with a grim prognosis, was started on metformin following a phenotypic drug screen that identified the related drug phenformin as active against her tumour [ 72 ]. Treatment at a relatively low dose of 1000 mg/day was associated with an objective response that lasted for nine months.…”

Section: Drugging the Undruggablementioning

confidence: 99%

Inhibiting the Priming for Cancer in Li-Fraumeni Syndrome

Pantziarka

Blagden

2022

Cancers

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The concept of the pre-cancerous niche applies the ‘seed and soil’ theory of metastasis to the initial process of carcinogenesis. TP53 is at the nexus of this process and, in the context of Li-Fraumeni Syndrome (LFS), is a key determinant of the conditions in which cancers are formed and progress. Important factors in the creation of the pre-cancerous niche include disrupted tissue homeostasis, cellular metabolism and chronic inflammation. While druggability of TP53 remains a challenge, there is evidence that drug re-purposing may be able to address aspects of pre-cancerous niche formation and thereby reduce the risk of cancer in individuals with LFS.

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Efficacy of oral metformin in a patient with metastatic adrenocortical carcinoma: Examination of mechanisms and therapeutic implications

Cited by 5 publications

References 38 publications

A Comparative Study between the Three Waves of the Pandemic on the Prevalence of Oropharyngeal Dysphagia and Malnutrition among Hospitalized Patients with COVID-19

A Comparative Study between the Three Waves of the Pandemic on the Prevalence of Oropharyngeal Dysphagia and Malnutrition among Hospitalized Patients with COVID-19

The role of an anti-diabetic drug metformin in the treatment of endocrine tumors

Inhibiting the Priming for Cancer in Li-Fraumeni Syndrome

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