Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors

Altieri, Barbara; Barrea, Luigi; Modica, Roberta; Bottiglieri, Filomena; Cicco, Federica de; Muscogiuri, Giovanna; Circelli, Luisa; Savarese, Giovanni; Somma, Carolina Di; Savastano, Silvia; Colao, Annamaria; Faggiano, Antongiulio

doi:10.1007/s12020-021-02869-w

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…This demonstrates that low VDR levels in ECs promote the development of endocrine tumors (gastrointestinal carcinoid tumors) in the midgut, consistent with findings of previous studies. Case studies in patients with intestinal carcinoid tumors have shown that VitD deficiency is common [55][56][57]. An association between VDR polymorphisms and the risks and outcomes of several malignancies such as colon cancer has been reported [34,35].…”

Section: Discussionmentioning

confidence: 99%

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

Park,

Na,

Kim

2024

Aging

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Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells' environment. Age-and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor pathway contributes to anti-aging and extends life expectancy are not well understood. In this study, we aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging. By utilizing a wellestablished Drosophila midgut model for stem cell aging biology, we revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age-and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.

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Section: Discussionmentioning

confidence: 99%

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

Park,

Na,

Kim

2024

Aging

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“…Particularly, phosphoremia levels were lower in NF1 patients, though within the normal range. The lower phosphoremia could be related to the lower vitamin D and higher PTH levels observed in NF1 patients [ 25 ]. However, the clinical meaning of this finding is unclear and has to be confirmed and explained in further studies.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical assessment included sex, age, BMI for both patients and controls, and evaluation of the 7 main clinical features according to NIH criteria for NF1 patients. BMI was calculated by weight and height (weight (kg) divided by height squared (m 2 ), kg/m 2 ] following standard criteria [ 24 , 25 ]. According to WHO’s criteria, patients were classified by BMI as normal weight (BMI 18.5–24.9 kg/m 2 ), overweight (BMI 25.0–29.9 kg/m 2 ), and obese (BMI ≥ 30.0 kg/m 2 [ 24 ].…”

Section: Experimental Designmentioning

confidence: 99%

Vitamin D and Bone Metabolism in Adult Patients with Neurofibromatosis Type 1

et al. 2023

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Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients.

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“…Clinical characteristics, including age, sex, anthropometric measurements (i.e., height and weight), symptoms at diagnosis, smoking habits, comorbidities, tumor size, imaging procedures, type of surgical resection, assessment of lymph nodes metastasis, pathological tumor stage, adjuvant treatment, as well as follow-up and patient outcome were collected from medical records. Body mass index (BMI) was evaluated from the anthropometric measurements and was classified according to the WHO criteria as normal weight (BMI 18.5–24.9 kg/m 2 ), overweight (BMI 25.0–29.9 kg/m 2 ), and obesity (BMI ≥ 30.0 kg/m 2 ), as previously reported [ 27 , 28 , 29 ]. Symptoms at diagnosis were considered tumor mass-related or hormonal-related.…”

Section: Methodsmentioning

confidence: 99%

Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection

Altieri

Salvia

Modica

et al. 2023

JPM

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Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. Results: 39 patients (M:F = 26:13), with a median age of 64 years (44–83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4–169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46–12.07, p = 0.008 and HR = 13.56, 95%CI 2.45–74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23–38.83, p = 0.002 and HR = 11.88, 95%CI 2.28–61.84, p = 0.003, respectively). Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.

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Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors

Cited by 8 publications

References 54 publications

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

Vitamin D and Bone Metabolism in Adult Patients with Neurofibromatosis Type 1

Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection

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