Concentrations of trace elements and <i>KRAS</i> mutations in pancreatic ductal adenocarcinoma

Gómez-Tomás, Álvaro; Pumarega, José; Alguacil, Juan; Amaral, André F.S.; Malats, Núria; Pallarès, Natàlia; Gasull, Magda; Porta, Miquel

doi:10.1002/em.22296

Cited by 18 publications

(34 citation statements)

References 73 publications

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“…Although Ni is considered a carcinogen, it has been shown to exhibit an inverse correlation between Ni content and the incidence of PC (31,32). One report demonstrated a positive correlation between Ni content and PC involving KRAS mutations (51). There is a mounting body of evidence that supports Ni involvement in an array of pancreasrelated dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of organic and inorganic nickel in pancreatic cell cultures: Comparison to cadmium

Wallace¹,

Buha-Đorđević²,

Benton³

2020

Arhiv za farmaciju

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Nickel compounds are Group 1 carcinogens and possibly cancer-causing in the pancreas. We examined the toxicity of nickel in both 2-D and 3-D pancreatic cell cultures, to determine the LD50 for organic and inorganic nickel in normal and cancerous cells. Assays with cadmium chloride were performed to be a comparison to potential nickel-induced toxicity. Cells were exposed to twelve concentrations of NiCl2 or Ni-(Ac)2 for 48h (2-D), or six concentrations for 48 hours (3-D). There was a significant (P=0.0016) difference between HPNE and AsPC-1 LD50 values after cadmium exposure, at 69.9 µM and 29.2 µM, respectively. Neither form of nickel exhibited toxicity in 2-D or 3-D cultures, but after 48h, changes in spheroid morphology were observed. The inability of Ni to reduce viable cell numbers suggests a toxic mechanism that differs from cadmium, also a Group 1 carcinogen. The cell microenvironment was not a factor in nickel toxicity with no changes in viable cells in either 2-D or 3-D cultures. These studies only examined cytotoxicity, and not genotoxicity, a potential mechanism of nickel carcinogenicity. Alterations in DNA function or the expression of apoptotic proteins/processes would take longer to manifest. Current work focuses on cellular changes following extended nickel exposure.

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Section: Discussionmentioning

confidence: 99%

Toxicity of organic and inorganic nickel in pancreatic cell cultures: Comparison to cadmium

Wallace¹,

Buha-Đorđević²,

Benton³

2020

Arhiv za farmaciju

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“…However, large amounts of whole grains, which are good sources of Se, including whole meal pasta and wheat, sourdough bread, stoneground wheat bread, and brown rice, are recommended by the MD (135). Higher levels of Se appeared protective for both mutated and KRAS wild-type PDAC (136). Amaral et al (137) found that high concentrations of Se were inversely associated with the risk of exocrine PC.…”

Section: Micronutrients and Pcmentioning

confidence: 99%

Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

Zhang

Yang

et al. 2021

Front. Oncol.

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Pancreatic cancer (PC) is a malignant tumor with high invasiveness, easy metastatic ability, and chemoresistance. Patients with PC have an extremely low survival rate due to the difficulty in early diagnosis. It is estimated that nearly 90% of PC cases are caused by environmental risk factors. Approximately 50% of PC cases are induced by an unhealthy diet, which can be avoided. Given this large attribution to diet, numerous studies have assessed the relationship between various dietary factors and PC. This article reviews three beneficial diets: a ketogenic diet (KD), a Mediterranean diet (MD), and a low-sugar diet. Their composition and impact mechanism are summarized and discussed. The associations between these three diets and PC were analyzed, and we aimed to provide more help and new insights for the prevention and treatment of PC.

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“…Second, in the specific presence of catalytic metals, such as iron and copper, vitamin C may become a pro-oxidant and behave as an anti-cancer agent, e.g., via production of H 2 O 2 [ 196 , 197 ]. Levels of both copper and iron tend to be higher in PDAC [ 198 , 199 ]. Accordingly, vitamin C may exert a protective role against PDAC.…”

Section: Dietary Considerationsmentioning

confidence: 99%

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

Jentzsch

Davis

Djamgoz

2020

Cancers

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The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.

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Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

Cited by 18 publications

References 73 publications

Toxicity of organic and inorganic nickel in pancreatic cell cultures: Comparison to cadmium

Toxicity of organic and inorganic nickel in pancreatic cell cultures: Comparison to cadmium

Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

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