Insulinoma: Literature’s Review (2)

AlJadir, Saadi Js

doi:10.15406/emij.2015.02.00031

Cited by 3 publications

(2 citation statements)

References 90 publications

(56 reference statements)

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“…However, in some patients, they may develop metastatic disease several years after the excision of insulinomas [ 6 , 7 ]. Despite the availability of multimodal treatment options, including surgery, chemotherapy, embolization, radiofrequency ablation, somatostatin analogs, insulin secretion inhibitors, and mTOR or tyrosine kinase inhibitors, the prognosis of malignant insulinoma is poor and the median survival is approximately 2 years [ 8 , 9 ]. Chemotherapy-based treatment of malignant insulinomas relies on the co-administration of streptozotocin and doxorubicin and/or 5-fluorouracil (5-FU), which may reduce hormonal symptoms in 6 to 70% of metastatic insulinoma patients [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

Filip

Lewińska

Adamczyk‐Grochala

et al. 2022

Cells

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5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic action of 5-azaC was observed in cells treated with the oxidant. On the contrary, 5-azaC stimulated an autophagic response, as demonstrated by the increase in phosphorylated eIF2α and elevated pools of autophagic marker LC3B in oxidant-treated β-TC-6 cells. Notably, autophagy resulted in increased necrotic cell death in β-TC-6 cells with higher levels of nitric oxide compared to less affected NIT-1 cells. In addition, 5-azaC increased levels of RNA methyltransferase Trdmt1, but lowered 5-mC and m6A levels, suggesting Trdmt1 inhibition. We postulate that the 5-azaC anticancer action may be potentiated during oxidative stress conditions that can be used to sensitize cancer cells, at least insulinoma cells, with limited drug responsiveness.

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Section: Introductionmentioning

confidence: 99%

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

Filip

Lewińska

Adamczyk‐Grochala

et al. 2022

Cells

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“…При инсулиноме значимым эффектом может обладать сочетание эверолимуса с октреотидом или сунитиниба с октреотидом. В качестве химиотерапии при злокачественных инсулиномах может быть использовано совместное введение стрептозоцина и доксорубицина и/или 5-фторурацила, что уменьшает степень выраженности симптомов у 60–70% пациентов [ 45 ]. Многообещающей является также схема FOLFOX, включающая сочетание 5-фторурацила с оксалиплатином.…”

Section: комплексная терапия злокачественных в том числе метастатичес...unclassified

Current views on the treatment of insulinoma

Chernykh,

Malyugin,

Khachaturov

et al. 2024

Probl Endokrinol (Mosk)

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Relevance: Insulinoma is the most common hormonally active neuroendocrine tumor (NET) of the pancreas. In recent years, there has been a trend towards an increase in the incidence of NET especially insulinoma.Aim: Summarizing and analyzing current data on various approaches to the treatment of insulinoma. Our review includes a comprehensive assessment of the advantages and disadvantages of currently available insulinoma treatment methods in comparison with past experience, as well as a review of promising methods that are not currently widely used.Materials and methods: Analysis of literature from such databases as scientific electronic library elibrary.ru, Pubmed, Google Scholar, MedLine, Scopus and Web of Science.Results: The most common treatment for insulinoma is surgery. For patients with high operative risk, alternative methods such as alcohol ablation, radiofrequency ablation, and tumor embolization may be used. Medications include the use of somatostatin analogues, diazoxide. The literature describes the potential benefit of the use of beta-blockers, phenytoin, glucagon, however, in clinical trials, these drugs have not demonstrated a significant effect. For the treatment of malignant and metastatically advanced insulinoma, targeted therapy (primarily Everolimus), chemotherapy, as well as embolization (including chemoembolization, radioembolization), radiofrequency ablation (RFA), microwave ablation and cryoablation, ultrasound ablation (HIFU), laser ablation, brachytherapy, irreversible electroporation are used.Conclusion: The study of new drugs is an important task for scientists, among medications the most promising are new generations of somatostatin analogues, targeted drugs and chemotherapy drugs. The rare frequency of insulinoma makes it difficult to conduct randomized controlled trials and prospective studies. That is why physicians and scientists need to maintain close contacts with each other and take into account the experience of treating each patient with such disease, which will help develop effective treatment algorithms in the future.

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Insulinoma: Literature’s Review (Part 1)

AlJadir¹

2015

EMIJ

Self Cite

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Insulinoma is rare a tumor of the islet cell of the pancreas that produces excessive amounts of insulin, inappropriately to plasma glucose levels. The average age of onset 40-50 years .The typical symptoms that patients complain about are related to the development of hypoglycemia. Patients with insulinoma usually develop neuroglycopenic symptoms (confusion, headache, visual difficulties, irrational behavior and extremely, coma) particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and eventually neurological damage. Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e., tremulousness, palpitations, tachycardia, sweating, hunger, anxiety) are not uncommon. Weight gain is sometimes observed and not uncommonly the patient might become massively obese. Insulinomas are small in 90% <2cm, solitary >90 %, and 5-10% malignant. They are almost invariably occur in the pancreas and distributed equally in head, body and tail. Insulinoma should be suspected in all patients with hypoglycemia, especially those with attacks provoked by fasting or with a family history of MEN-1. The diagnosis of an insulinoma is usually made biochemically with low blood glucose, elevated insulin, C-peptide levels and proinsulin, by a 72-hour fasting under close supervision, and confirmed by localizing the tumor by computed tomography, MRI, or transabdominal and endoscopic ultrasonography. Sometimes detection of lesions might be challenging and ancillary tests are occasionally required. The definitive treatment is surgical removal of the tumor, and laparoscopic surgery for localized lesions is increasingly reported. Medical treatment is reserved for unresectable tumors, preoperative preparation or for unsuitable candidates for surgery.

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Insulinoma: Literature’s Review (2)

Cited by 3 publications

References 90 publications

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

Current views on the treatment of insulinoma

Insulinoma: Literature’s Review (Part 1)

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