• Bioactive vitamin D3 conjugate
• Esterase-activatable micelle
• Intracellular drug delivery
• Paclitaxel
• Pancreatic ductal adenocarcinoma

• ATRA
• Ascorbic acid
• Calcitriol
• Cancer
• Pancreatic cancer
• Vitamins

• tumour heterogeneity
• pancreatic cancer

• Animals
• Mice
• Vitamin D/pharmacology
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/metabolism
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Azacitidine/pharmacology
• Epigenesis, Genetic
• Gene Expression Profiling
• Cell Line, Tumor
• Cell Proliferation
• Gene Expression Regulation, Neoplastic

• RSG-20-036-01 American Cancer Society (American Cancer Society, Inc.)

• 25-hydroxyvitamin D
• Meta-analysis
• Overall survival
• Pancreatic cancer
• Prognostic marker

• Humans
• Vitamin D
• Calcifediol
• Prognosis
• Pancreatic Neoplasms

The only potential curative treatment for patients with pancreatic cancer is surgery; however, the prognosis remains poor. Measures of body composition based on computed tomography (CT) have been established as a reliable predictor of the prognosis of cancer patients after surgery.

To elucidate the associations of body composition measures derived from preoperative CT scans with the prognosis of patients with pancreatic cancer.

One hundred fifteen patients undergoing pancreatic resection with curative intent for pancreatic cancer were retrospectively enrolled. A preoperative CT scan at the third lumbar vertebral level was performed to measure the skeletal muscle index (SMI), mean skeletal muscle radiodensity, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratio. The clinical and pathological data were collected. The effects of these factors on long-term survival were evaluated.

Among the five body composition measures, only low SMI independently predicted overall survival (OS) [hazard ratio (HR): 2.307; 95% confidence interval (CI): 1.210-4.402] and recurrence-free survival (HR: 1.907; 95%CI: 1.147-3.171). Furthermore, patients with low SMI (vs high SMI) were older (68.8 ± 9.3 years vs 63.3 ± 8.4 years); low SMI was present in 27 of 56 patients (48.2%) aged 65 years and older and in 11 of 59 younger patients (18.6%). In addition, subgroup analyses revealed that the correlation between low SMI and OS was observed only in patients aged 65 years and older.

Low preoperative SMI was more prevalent in elderly patients and was associated with a poor prognosis among pancreatic cancer patients, especially elderly patients.

• Pancreatic cancer
• Body composition
• Elderly
• Skeletal muscle index
• Prognosis

Thyroid cancer is the most common endocrine malignancy in the United States and papillary thyroid cancer is by far the most common subtype. Vitamin D has been postulated as a key modulator in several cancer-related pathways, although its contributions to thyroid cancer remain controversial. In this paper, we review the metabolic pathways of vitamin D and explore potential links to cancer-related mechanisms. In addition, we also explore the medical literature related to vitamin D as a prognostic marker for staging in papillary thyroid cancer.

The role of vitamin D in modulating several cancer-related pathways has received an increasing amount of attention in the past several years. Previous literature has found an abundance of evidence of vitamin D exerting an anti-proliferative, anti-inflammatory, and pro-differentiation effect in various types of cancers including breast, colon, prostate, and pancreatic cancer. Although the link between vitamin D and thyroid cancer remains controversial, both biochemical evidence and clinical studies have attempted to establish a link between papillary thyroid carcinoma (PTC) and vitamin D status. Furthermore, the use of vitamin D as a prognostic marker has received increased attention, both in regards to clinical outcomes and cancer staging. In this review, we briefly discuss the metabolism and proposed mechanism of action of vitamin D in the context of PTC, and explore links between modulators in the vitamin D pathway and progression of PTC. We provide evidence from both clinical studies as well as molecular studies of metabolic targets, including vitamin D receptor and activating enzymes exerting an effect on PTC tissue, which indicate that vitamin D may play a significant prognostic role in PTC.

• papillary thyroid carcinoma
• prognosis
• staging
• vitamin D

• TGF beta
• cell motility
• cell proliferation
• epithelial–mesenchymal transition
• human pancreatic cancer
• mitochondria
• reactive oxygen species
• respiratory chain
• vitamin D receptor

Recent efforts in the field of nutritional science have allowed the discovery of disease-beating molecules within foods based on the commonality of bioactive food molecules to FDA-approved drugs. The pioneering work in this field used an unsupervised network propagation algorithm to learn the systemic-wide effect on the human interactome of 1962 FDA-approved drugs and a supervised algorithm to predict anticancer therapeutics using the learned representations. Then, a set of bioactive molecules within foods was fed into the model, which predicted molecules with cancer-beating potential.The employed methodology consisted of disjoint unsupervised feature generation and classification tasks, which can result in sub-optimal learned drug representations with respect to the classification task. Additionally, due to the disjoint nature of the tasks, the employed approach proved cumbersome to optimize, requiring testing of thousands of hyperparameter combinations and significant computational resources.To overcome the technical limitations highlighted above, we represent each drug as a graph (human interactome) with its targets as binary node features on the graph and formulate the problem as a graph classification task. To solve this task, inspired by the success of graph neural networks in graph classification problems, we use an end-to-end graph neural network model operating directly on the graphs, which learns drug representations to optimize model performance in the prediction of anticancer therapeutics.

The proposed model outperforms the baseline approach in the anticancer therapeutic prediction task, achieving an F1 score of 67.99%±2.52% and an AUPR of 73.91%±3.49%. It is also shown that the model is able to capture knowledge of biological pathways to predict anticancer molecules based on the molecules’ effects on cancer-related pathways.

We introduce an end-to-end graph convolutional model to predict cancer-beating molecules within food. The introduced model outperforms the existing baseline approach, and shows interpretability, paving the way to the future of a personalized nutritional science approach allowing the development of nutrition strategies for cancer prevention and/or therapeutics.

The online version contains supplementary material available at (10.1186/s40246-021-00333-4).

• Cancer research
• Genomics
• Graph deep learning
• Hyperfoods
• Systems biology

• breast cancer
• cell line
• colorectal cancer
• cytotoxic
• vitamin D

• 25-hydroxyvitamin D
• Biomarkers of inflammation
• C-reactive protein
• Interleukin-6
• Pancreatic cancer
• Prognosis
• Survival
• YKL-40

• PDAC
• cytokines
• immune system
• intracellular calcium
• intracellular signaling pathways
• vitamin D

• Cancer
• Vitamin D
• Vitamin D receptor

• 25(OH)D
• gestational diabetes mellitus
• meta-analysis
• vitamin D

Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in China. 1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃] has been shown to possess significant antitumor potential and is degraded by 25-hydroxyvitamin D-24-hydroxylase (CYP24A1). In the present study, the role of CYP24A1 and autophagy, and their underlying mechanisms in the anticancer effects of 1,25(OH)₂D₃ in DLBCL cells, were investigated. It was found that the levels of CYP24A1 in DLBCL lymph node tissues were higher than in hyperplasia lymphadenitis tissue. Moreover, the expression of CYP24A1 was positively associated with the Ann Arbor stage and the International Prognostic Index in patients with DLBCL, and negatively associated with the clinical response to treatment. Patients >60 years of age were found to have a higher level of CYP24A1. 1,25(OH)₂D₃ inhibited the proliferation of the Pfeiffer DLBCL cell line and increased the G1 phase population of Pfeiffer cells. Rapamycin (RAPA) in combination with 1,25(OH)₂D₃ increased the G1 phase distribution of Pfeiffer cells. Furthermore, RAPA blocked the increase of CYP24A1 and vitamin D receptor (VDR) expression induced by 1,25(OH)₂D₃. 1,25(OH)₂D₃ induced the formation of autophagosomes, increased the expression of autophagy related protein light chain (LC)3II/LC3I and reduced the expression of the ubiquitin binding protein P62. In addition, 1,25(OH)₂D₃ decreased the phosphorylation of AKT and mammalian target of RAPA (mTOR), and downstream targets eukaryotic translation imitation factor 4E-binding protein 1 and ribosomal protein S6 kinase β-1 in Pfeiffer cells. The results from the present study suggested that CYP24A1 may be a novel prognostic indicator for DLBCL. 1,25(OH)₂D₃ inhibited proliferation and induced autophagy of Pfeiffer cells. In addition, 1,25(OH)₂D₃ increased the G1 phase population of Pfeiffer cells. These effects may be mediated by inhibition of the AKT/mTOR/PI3K signaling pathway. RAPA increased the cell cycle arrest induced by 1,25(OH)₂D₃ by blocking the upregulated expression of CYP24A1 and VDR.

• eye cancer
• predictive markers
• prognostic markers
• outcomes research

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism
• Adult
• Aged
• Aged, 80 and over
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Melanins/metabolism
• Melanoma/metabolism
• Middle Aged
• Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism
• Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
• Receptors, Calcitriol/metabolism
• Uvea/metabolism
• Uveal Neoplasms/metabolism
• Vitamin D3 24-Hydroxylase/metabolism

• I01 BX004293 BLRD VA
• R01 AR071189 NIAMS NIH HHS
• R01 AR073004 NIAMS NIH HHS
• Z01 ES101586 Intramural NIH HHS
• EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
• U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)

• gastric cancer
• tumorigenesis
• vitamin D
• vitamin D receptor

Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too.

Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise.

The anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer.

• Anti-inflammatory
• Current therapies
• Liver disorders
• Vitamin D

• Diet
• Foods
• Nutrients
• Pancreatic cancer
• Pancreatic cancer risk

• 25-hydroxyvitamin D
• mortality
• pancreatic cancer
• risk
• vitamin D

• Cohort Studies
• Global Health/statistics & numerical data
• Humans
• Incidence
• Pancreatic Diseases/epidemiology
• Pancreatic Diseases/mortality
• Regression Analysis

Vitamin D deficiency is implicated in neoplastic processes in multiple organs, including the pancreas. While animal and human data have established a relationship between serum vitamin D (25(OH)D) and the development of pancreatic cancer, few studies have examined the effects of 25(OH)D on time to progression (TTP) and overall survival (OS) in this patient population. We hypothesize that lower baseline serum concentrations (BSC) of 25(OH)D will be associated with decreased TTP and OS.

This retrospective analysis of 1222 patients with pancreatic cancer aims to identify potential relationships between 25(OH)D and both TTP and OS, while controlling for the effects of ethnicity and body mass index (BMI). Baseline 25(OH)D was divided into quartiles defined as deficient (<20 ng/mL), insufficient (20–39 ng/mL), sufficient (40–59 ng/mL), and optimal (≥60 ng/ml). Statistical significance was declared if the two-sided p-value was ≤ 0.05.

For the 627 subjects included for analysis, the median 25(OH)D was 27 ng/mL (range 4 to 114), 30.0 % were 25(OH)D deficient (<20 ng/mL), and 47.2 % were insufficient (20–39 ng/mL). Ethnicity (p < 0.0001) and BMI (p = 0.05) were significantly associated with (BSC)of 25(OH)D, while TTP (p = 0.39) and OS (p = 0.37) were not associated.

Suboptimal vitamin D levels (<60 ng/mL) occurred in 96 % of patients analyzed. Both ethnicity and BMI were statistically significantly associated with vitamin D deficiency and insufficiency. Similar to results previously reported in the literature, this analysis did not identify a significant association between BSC of 25(OH)D and OS or TTP in patients with pancreatic cancer.

Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

• cancer prevention
• diet
• obesity
• pancreatic cancer