scholarly journals Single-cell analyses unravel cell type–specific responses to a vitamin D analog in prostatic precancerous lesions

2021 ◽  
Vol 7 (31) ◽  
pp. eabg5982
Author(s):  
Mohamed A. Abu el Maaty ◽  
Elise Grelet ◽  
Céline Keime ◽  
Anna-Isavella Rerra ◽  
Justine Gantzer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Single Cell ◽  
Precancerous Lesions ◽  
Matrix Remodeling ◽  
Sequencing Analysis ◽  
C Cells ◽  
Anticancer Activities ◽  
Stromal Fibroblasts ◽  
Vitamin D Analog ◽  
The Impact

Epidemiological data have linked vitamin D deficiency to the onset and severity of various cancers, including prostate cancer, and although in vitro studies have demonstrated anticancer activities for vitamin D, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically engineered Pten(i)pe−/− mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment’s efficacy.

scholarly journals Influence of Estrogen Treatment on ESR1+ and ESR1− Cells in ER+ Breast Cancer: Insights from Single-Cell Analysis of Patient-Derived Xenograft Models

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6375
Author(s):  
Hitomi Mori ◽  
Kohei Saeki ◽  
Gregory Chang ◽  
Jinhui Wang ◽  
Xiwei Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Therapy Response ◽  
Sequencing Analysis ◽  
Gene Set ◽  
Patient Derived Xenograft ◽  
Potential Marker ◽  
The Impact

A 100% ER positivity is not required for an endocrine therapy response. Furthermore, while estrogen typically promotes the progression of hormone-dependent breast cancer via the activation of estrogen receptor (ER)-α, estrogen-induced tumor suppression in ER+ breast cancer has been clinically observed. With the success in establishing estrogen-stimulated (SC31) and estrogen-suppressed (GS3) patient-derived xenograft (PDX) models, single-cell RNA sequencing analysis was performed to determine the impact of estrogen on ESR1+ and ESR1– tumor cells. We found that 17β-estradiol (E2)-induced suppression of GS3 transpired through wild-type and unamplified ERα. E2 upregulated the expression of estrogen-dependent genes in both SC31 and GS3; however, E2 induced cell cycle advance in SC31, while it resulted in cell cycle arrest in GS3. Importantly, these gene expression changes occurred in both ESR1+ and ESR1– cells within the same breast tumors, demonstrating for the first time a differential effect of estrogen on ESR1– cells. E2 also upregulated a tumor-suppressor gene, IL-24, in GS3. The apoptosis gene set was upregulated and the G2M checkpoint gene set was downregulated in most IL-24+ cells after E2 treatment. In summary, estrogen affected pathologically defined ER+ tumors differently, influencing both ESR1+ and ESR1– cells. Our results also suggest IL-24 to be a potential marker of estrogen-suppressed tumors.

scholarly journals Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8171
Author(s):  
Ling-Yu Huang ◽  
Yi-Ping Hsieh ◽  
Yen-Yun Wang ◽  
Daw-Yang Hwang ◽  
Shih Sheng Jiang ◽  
...  
Keyword(s):  
Drinking Water ◽  
Oral Cancer ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Precancerous Lesions ◽  
Enrichment Analysis ◽  
Normal Mucosa ◽  
Gene Set Enrichment Analysis ◽  
Control Group ◽  
Sequencing Analysis

Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg/L) and arecoline (500 mg/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target.

scholarly journals Single-Cell RNA-seq Reveals Obesity-Induced Alterations in the Brca1-Mutated Mammary Gland Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2235
Author(s):  
Pang-Kuo Lo ◽  
Yuan Yao ◽  
Qun Zhou
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cells ◽  
Experimental Studies ◽  
Cell Communication ◽  
Mammary Glands ◽  
Breast Tumorigenesis ◽  
Stromal Fibroblasts ◽  
The Impact

Clinical and experimental studies have shown that obesity increases the development and progression of breast cancer. The impact of obesity on the tumor microenvironment plays an important role in tumorigenesis, yet the precise mechanisms underlying obesity-mediated effects on cell-to-cell communication within the tumor microenvironment have been difficult to define. In this study, we conducted single-cell RNA sequencing (scRNA-seq) studies to investigate the impact of high-fat diet (HFD)-induced obesity on transcriptomic landscapes of stromal and immune cells in mammary glands of Brca1−/−; p53+/− mice, an animal breast cancer model. Hierarchical clustering and gene pathway enrichment analyses of scRNA-seq data showed that five different subtypes of stromal fibroblasts existed in mouse Brca1-mutated mammary glands. HFD-induced obesity led to upregulated expression of extracellular matrix (ECM) genes (Col3a1, Col6a3, Eln, and Sparc) and downregulated expression of immunoregulatory genes (Iigp1 and Cxcl10) in these stromal subtype cells. These findings, taken together, suggest that obesity alters the ECM composition and immune ecosystem through modulating the functionality of mammary stromal fibroblasts. Moreover, scRNA-seq analysis of mammary immune cells indicated that HFD-induced obesity promoted the generation and/or recruiting of pro-tumorigenic M2 macrophages in mammary glands. Our studies provide new insight into a mechanistic paradigm wherein obesity modulates the functions of stromal and immune cells to create the tumorigenic microenvironment for promoting breast tumorigenesis.

190: BXL-628, a Vitamin D Analog, Decreases RHOA/ROK Signalling in Rat and Human Bladder

2006 ◽  
Vol 175 (4S) ◽  
pp. 62-62
Author(s):  
Annamaria Morelli ◽  
Sandra Filippi ◽  
Rosa Mancina ◽  
Linda Vignozzi ◽  
Gabriella B. Vannelli ◽  
...  
Keyword(s):  
Vitamin D ◽  
Human Bladder ◽  
Vitamin D Analog

Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis

2020 ◽  
pp. 1-8
Author(s):  
Hasan Haci Yeter ◽  
Berfu Korucu ◽  
Elif Burcu Bali ◽  
Ulver Derici
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Antioxidant Status ◽  
Total Antioxidant Status ◽  
Stress Index ◽  
Total Oxidant Status ◽  
Vitamin D Analog ◽  
Total Antioxidant ◽  
Oxidant Status ◽  
And Oxidative Stress

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

2020 ◽  
Vol 26 (21) ◽  
pp. 2492-2496 ◽  
Author(s):  
Fiammetta Romano ◽  
Giovanna Muscogiuri ◽  
Elea Di Benedetto ◽  
Volha V. Zhukouskaya ◽  
Luigi Barrea ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sleep Disorders ◽  
Vitamin D Deficiency ◽  
Sleep Apnea Syndrome ◽  
Regulatory Mechanisms ◽  
Sleep Regulation ◽  
Vitamin D Receptors ◽  
Obstructive Sleep ◽  
The Impact

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. Conclusions: : Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

scholarly journals Vitamin D and Blood Parameters

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1017
Author(s):  
Thomas Müller ◽  
Lutz Lohse ◽  
Andreas Blodau ◽  
Katja Frommholz
Keyword(s):  
Vitamin D ◽  
Mean Corpuscular Volume ◽  
Plasma Concentrations ◽  
Blood Parameters ◽  
Vitamin D Supplementation ◽  
Mean Corpuscular Hemoglobin ◽  
Corpuscular Volume ◽  
Corpuscular Haemoglobin ◽  
Mean Corpuscular Haemoglobin ◽  
The Impact

Background: Vitamin D has a steroid- and an anabolic-resembling chemical structure. Vitamin D is essential for many processes in the human body after hydroxylation. Aims of the Study: To investigate the impact of 25-hydroxy-vitamin D plasma concentrations on the blood parameters number of erythrocytes, hematocrit, mean corpuscular hemoglobin and mean corpuscular volume. Methods: Serial assessments were done in 290 patients with multiple sclerosis and repeated after a mean interval of 245 days. A recommendation for vitamin D supplementation was given in case of a concentration lower than 20 ng/mL combined with a prescription of a formulation containing vitamin D but not vitamin K. Results: There was a fall of vitamin D in 119 subjects and a rise in 164, while no change appeared in 7 participants. When vitamin D values went down between both assessments moments, the computed increase of mean corpuscular haemoglobin was significantly lower compared with the rise of mean corpuscular haemoglobin associated with a vitamin D elevation. When vitamin D declined, the computed fall of mean corpuscular volume fall was significantly lower compared with the decrease of mean corpuscular volume, when vitamin D rose. Positive correlations were found between differences of vitamin D and mean corpuscular haemoglobin, respectively mean corpuscular volume. Inverse relations appeared between disparities of vitamin D and erythrocytes, respectively haematocrit. Conclusions: The elevation of vitamin D plasma levels provides enhanced preconditions for a better tissue oxygenation on a cellular level.

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