Vitamin D Receptor, Retinoid X Receptor, Ki-67, Survivin, and Ezrin Expression in Canine Osteosarcoma

Canine osteosarcoma (OS) is an aggressive malignant bone tumor. Prognosis is primarily determined by clinical parameters. Vitamin D has been postulated as a novel therapeutic option for many malignancies. Upon activation, vitamin D receptors (VDRs) combine with retinoid receptor (RXR) forming a heterodimer initiating a cascade of events. Vitamin D's antineoplastic activity and its mechanism of action in OS remain to be clearly established. Expression of VDR, RXR, Ki-67, survivin, and ezrin was studied in 33 archived, canine OS specimens. VDR, RXR, survivin, and ezrin were expressed in the majority of cases. There was no statistically significant difference in VDR expression in relationship with tumor grade, type, or locations or animal breed, age, and/or sex. No significant association (p=0.316) between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and VDR expression (ρ=−0.466), a positive correlation between survivin and RXR expression was found (p=0.374). A significant relationship exists between VDR and RXR expression in OSs and proliferative/apoptosis markers. These results establish a foundation for elucidating mechanisms by which vitamin D induces antineoplastic activity in OS.

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Retrospective immunohistochemical study of VDR, RXR, Ki-67, and Bcl-2 expression in primary and metastatic osteosarcoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e21516 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e21516-e21516 ◽

Cited By ~ 1

Author(s):

O. Tawfik ◽

R. Garimella ◽

J. Tancabelic ◽

J. Keighley ◽

D. Pinson ◽

...

Keyword(s):

Proliferative Activity ◽

Therapeutic Option ◽

Immunohistochemical Analysis ◽

Antineoplastic Activity ◽

Retinoid Receptor ◽

Ki 67 ◽

Primary Tumors ◽

Cellular Events ◽

Biologic Effect ◽

Histologic Types

e21516 Background: Osteosarcoma (OS) is a highly malignant tumor with a peak incidence in adolescents and young adults. Patient's prognosis is limited to clinical parameters whereas molecular markers of tumor aggression are yet to be identified. Vitamin D (Vit D) has been postulated as a novel therapeutic option for a variety of malignancies such as breast and prostatic carcinomas. The biologic effect of vitamins is mainly mediated through receptors. Vit D receptors (VDRs) are members of the steroid hormone superfamily and are ubiquitous in a various tissues including bone. Upon activation by its ligand, VDR combines with retinoid receptor (RXR) forming a heterodimer initiating a cascade of cellular events. How Vit D induces its antineoplastic activity in OS remains to be elucidated. Methods: Immunohistochemical analysis for VDR, RXR, Ki-67, and bcl-2 was performed on 87 OS specimens to evaluate differentiation, proliferation and apoptosis. Clinical data including site of the primary tumor, presence or absence of metastasis, therapeutic regimens, and outcome were recorded. Results: The mean age of OS patients is 25.7 years (range 7–68). Fifty-four patients were <30 years. Thirty-five OSs were conventional, 17 chondroblastic, 6 giant cell, 6 fibroblastic, 6 mixed, 3 telangiectatic, and 2 epithelioid variants. Twelve of the 87 samples were metastatic. All metastatic OSs were high grade, located in the lungs with a mean age of 25 years (range 7–52). The majority of the OSs expressed VDR (74/87, 85%) and RXR (72/78, 92%). Proliferative activity varied between tumors types with highest Ki-67 percentage noticed in conventional variant (29%), followed by chondroblastic variant (16%). Metastatic tumors consistently had the highest proliferative activity as compared to primary tumors (35%). None of the tumors studied was immunoreactive for bcl-2. Conclusions: Our results demonstrate that VDR and RXR are expressed on most OSs. A significant relationship exists between tumor histologic types and proliferative activity. Metastatic OSs appears to have a significantly higher level of proliferative activity as compared to primary tumors. These results would establish a foundation for elucidating mechanisms by which Vit D induces its antineoplastic activity in OS. No significant financial relationships to disclose.

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THE EFFECTS OF CURCUMIN AND VITAMIN D COMBINATION AS INHIBITOR TOWARD SALMONELLA TYPHI BACTERIA GROWTH IN VIVO

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019.v11s5.t0093 ◽

2019 ◽

pp. 116-120

Author(s):

AMI FEBRIZA ◽

VIVIEN NOVARINA A KASIM ◽

HASTA HANDAYANI IDRUS ◽

MOCHAMMAD HATTA

Keyword(s):

Vitamin D ◽

Typhoid Fever ◽

Antimicrobial Effect ◽

Control Groups ◽

Post Intervention ◽

Asian Continent ◽

Vitamin D Receptors ◽

Group I ◽

Significant Difference

Objectives: The prevalence of typhoid fever was reportedly high, especially in the Asian continent, as many as 80% of cases came from slums inBangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and Vietnam. Due to many cases of antibiotic resistance in typhoid fever, various effortshave been made by combining antibiotic therapy or active compounds with adjuvants and herbs. Curcumin is an active compound found in manyherbal plants, especially in the Asian Continent. Curcumin has an antimicrobial effect, presumably due to its ability to bind Vitamin D receptors (VDR)as a potential ligand. This condition increases the expression of cathelicidin antimicrobial peptides and eradicates bacteria. Vitamin D will definitelybind to VDR as well; on this basis, this study wants to prove the effect of the combination of curcumin and Vitamin D therapy in inhibiting the growthof Salmonella typhi.Methods: This study is a true experimental pre- and post-test design using colony calculation method to investigate the effectiveness of curcumin andVitamin D in suppressing the growth of S. typhi bacteria in peritoneal fluid male mice strain balb/c. Mice were divided into five groups randomly, namely,the negative control groups, Group I (curcumin 200 mg/BB/day), Group II (curcumin 400 mg/BB/day), and Group III (curcumin 200 mg/BB/day andVitamin D 200 IU/day), and the positive control groups (antibiotic levofloxacin). The intervention was carried out for 5 days. After the 5th day, micewere then maintained for 3 weeks to determine the amount of colony growth in the post-intervention period.Results: The comparison of the results between each group gave significance in the average number of bacterial colonies of intraperitoneal fluid.Each group gave a significant difference of <0.05. Curcumin has an activity as an antimicrobial, the higher the dose, the greater the number of bacteriainhibited growth. After curcumin therapy, 200 mg/kg and 400 mg/kg for 5 days, a decrease in the number of bacterial colonies in the intraperitonealfluid was found. This study concluded that curcumin has an antimicrobial effect on S. typhi. The groups with combination therapy of Vitamin D andcurcumin intervention also gave the same results. Conclusion: Based on the results of this study, the combination of curcumin and Vitamin D is able to inhibit the growth of S. typhi bacteria, even upto 30 days after infection.

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Ki-67 and mitotic index in triple-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12551 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12551-e12551

Author(s):

Maria Mikhailovna Urezkova ◽

Tatiana Semiglazova ◽

Anna Artemyeva ◽

Asel Kudaybergenova

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Proliferative Activity ◽

Group Versus ◽

Tumor Grade ◽

Ki 67 ◽

Development Of Resistance ◽

Significant Difference ◽

Histological Malignancy ◽

Positive Breast Cancer

e12551 Background: A grade in breast cancer is the strongest prognostic factor. In the new edition of the AJCC 8th, the tumor grade is one of the criteria that determines patients with breast cancer in the prognostic groups. According to the Nottingham system the mitotic count (MC) mostly determines the grade. Interobserver reproducibility for MC is not as good as for IHC marker phh3. The group of triple-positive breast cancer (TPBC) is characterized by the presence of a crosstalk mechanism between the signaling pathways of ER and HER2, which leads to the development of resistance to therapy. However, according to the 8th AJCC, patients with ER+/HER2+ belong to a more favorable prognostic group. Methods: We selected 284 patients with early BC who received treatment at our centre from 2012 to 2020 and didn’t receive presurgical therapy. The patients were divided according to the surrogate subtype into triple-positive (n = 90) and other subtypes (n = 194). The Ki-67, the number of nuclei of tumor cells stained with anti-phh3 antibody, the cell density of the tumor per 1 mm2 and the number of phh3 + per 1000 tumor cells were assessed. Results: Visually accessed number of mitoses was grade 3 in 30% of tumors in the TPBC group and 29% in the second group. There was no statistically significant difference in the Ki-67 index of proliferative activity in the two studied groups. In the TPBC group the median Ki-67 was 16.8%, in the second group - 18.3% (p = 0.376516), while the groups differed significantly in terms of the phh3 index (the median in the TPBC was 23.7/mm2, the median in the second group - 16.06/mm2, p = 0.024703). The groups also significantly differed in the number of nuclei of tumor cells that directly entered the mitotic phase (5.1/1000 nuclei in the TPBC group versus 3.2/1000 nuclei in the second group, p = 0.003901). Conclusions: Despite similar indices of proliferative activity in the TPBC and non-TPBC groups, mitotic activity and the number of directly dividing tumor cells in the TPBC group are significantly higher than in the rest of the BC population. Considering the criteria for assessing phh3 (MC 1 < 4/mm2, MC 2 2 4 to 7/mm2, MC 3 > 7/mm2), most TPBCs will have a histological malignancy grade of 3, which according to AJCC 8th places them in the group of poor outcome. We suggest that these differences may be due to the crosstalk mechanism. The second conclusion of our study is the fact that Ki-67 is a poor predictor of the MC.

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Tumor grade 2 as the independent predictor for lymph node metastasis in 10–20 mm sized rectal neuroendocrine tumor

Korean Journal of Clinical Oncology ◽

10.14216/kjco.21006 ◽

2021 ◽

Vol 17 (1) ◽

pp. 37-43

Author(s):

Byung-Soo Park ◽

Sung Hwan Cho ◽

Gyung Mo Son ◽

Hyun Sung Kim ◽

Su Jin Kim ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Size ◽

Tumor Grade ◽

Radical Resection ◽

Independent Factor ◽

Ki 67 ◽

Node Metastasis ◽

Significant Difference ◽

National University

Purpose: Rectal neuroendocrine tumors (NETs) <10 mm are endoscopically resected, while those ≥20 mm are treated with radical surgical resection. The choice of treatment for 10–20 mm sized rectal NETs remains controversial. This study aimed to verify factors predicting lymph node metastasis (LNM) of 10–20 mm sized rectal NET and utilize them to decide upon the treatment strategy.Methods: Twenty-eight patients with 10–20 mm sized rectal NETs treated at Pusan National University Yangsan Hospital from January 2009 to September 2020 were divided into LNM (+) and LNM (–) groups, and their respective data were analyzed.Results: Seven patients (25%) had LNM while 21 patients (75%) did not. Endorectal ultrasound findings showed tumor size was significantly larger in the LNM (+) than in the LNM (–) group (15 mm vs. 10 mm, P=0.018); however, pathologically, there was no significant difference in tumor size (13 mm vs. 11 mm, P=0.109). The mitotic count (P=0.011), Ki-67 index (P=0.008), and proportion of tumor grade 2 patients (5 cases, 71% vs. 1 case, 5%; P=0.001) were significantly higher in the LNM (+) group. In multivariate analysis, tumor grade 2 was the independent factor predicting LNM (odds ratio, 61.32; 95% confidence interval, 3.17–1,188.64; P=0.010).Conclusion: Tumor grade 2 was the independent factor predicting LNM in 10–20 mm sized rectal NETs. Therefore, it could be considered as the meaningful factor in determining whether radical resection is necessary.

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Study of Vitamin D Receptor Levels in Children with Immune Thrombocytopenic Purpura

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2021/v7i230209 ◽

2021 ◽

pp. 1-6

Author(s):

Eman Abd Elkhalek Elnady ◽

Ibrahim Mohamed Badraia ◽

Adel Abd El-Haleim Hagag ◽

Sarah Amr Hamam

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Immune Thrombocytopenic Purpura ◽

Conventional Treatment ◽

Statistical Difference ◽

Vitamin D Supplementation ◽

Healthy Children ◽

Thrombocytopenic Purpura ◽

Vitamin D Receptors ◽

Significant Difference

Background: Vitamin D, affecting many tissues and organs of the body. It exerts many of its effects through contact with Vitamin D receptor (VDR) It Is Important especially in immune system; Immune thrombocytopenia is one of the most common causes of symptomatic thrombocytopenia in children. Aim: The main objective of our study was to study vitamin D receptor level in children with immune thrombocytopenic purpura and effect of vitamin D supplementation upon the response of the thrombocytopenia to conventional therapy of ITP. Subjects and Methods: This is a case control study which included 30 ITP children, who would be attendants to Hematology and Oncology Unit, Pediatric Department, Tanta University Hospital in Egypt. This study would include also 30 apparently healthy children matched in age and sex as a control group. The duration of the study ranges from 6 to 12 months, for all patients and controls the following were done: complete blood count, bone marrow aspiration, serum level of Vitamin D receptors, serum calcium level, serum phosphorus level, serum alkaline phosphatase level and serum parathyroid hormone level. Results: the results revealed that mean ± SD of Vitamin D receptors in case group is 132.43 ± 14.58 and there was statistical difference between groups regarding Vitamin D receptor. There was statistical difference between platelets count and Serum total Ca (mg/dl) with negative correlation, while there was no statistical difference between platelets count and Vitamin D receptor. There was statistically significant difference in platelets count in patient with ITP before and after conventional treatment and platelets count in patient with ITP under conventional treatment plus vitamin D supplementation. Conclusion: VD receptors elevation is very common in ITP. Supplementing VD might diminish recurrence. Further research is needed.

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Assessment of Serum Vitamin D Levels in Patients with Vitiligo in Jordan: A Case-Control Study

Dermatology Research and Practice ◽

10.1155/2019/2048409 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Diala M. Alshiyab ◽

Firas A. Al-qarqaz ◽

Leen H. Heis ◽

Jihan M. Muhaidat ◽

Wlla S. Eddin ◽

...

Keyword(s):

Vitamin D ◽

Case Control Study ◽

Skin Diseases ◽

Serum Vitamin ◽

Case Control ◽

Vitamin D Receptors ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Significant Difference ◽

Control Study

Background. Low vitamin D serum levels have been associated with many autoimmune disorders and several other skin diseases. Vitiligo is an autoimmune disease characterized by destruction of melanocytes by immune mechanisms. Melanocytes express vitamin D receptors, and their function can be affected by vitamin D status. Objectives. The main objective of this study is to compare vitamin D levels in patients with vitiligo vs normal population and whether vitamin D deficiency is associated with vitiligo. Methods. A case-control study was conducted. 100 vitiligo patients and 100 as controls were included in this study. Serum vitamin D level was measured for both vitiligo patients and controls, results were compared, and statistical analysis was done to compare the results. Results. The median age of vitiligo cases was 23 years (ranges, 2–80). 58% of vitiligo patients were females. The median vitamin D level was not significantly different between the two groups (vitiligo = 14.1 (IQR 9.9–20.4) vs control = 16.5 (IQR 10.3–25.3) (P=0.28)). Most vitiligo cases and controls were found to have low levels of vitamin D (either insufficient 20–30 ng/mL or low <20 ng/mL). Conclusions. There was no significant difference in vitamin D levels in vitiligo patients compared to controls. However, vitamin D levels were generally low in both groups.

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Factors predicting metastasis in patients with 10–20-mm sized rectal neuroendocrine tumor

10.21203/rs.3.rs-51218/v2 ◽

2020 ◽

Author(s):

Byung-Soo Park ◽

Sung Hwan Cho ◽

Gyung Mo Son ◽

Hyun Sung Kim ◽

Su Jin Kim ◽

...

Keyword(s):

Tumor Size ◽

Tumor Grade ◽

Radical Resection ◽

Ki 67 ◽

Appropriate Treatment ◽

Lymph Node Enlargement ◽

Significant Difference ◽

National University ◽

Rectal Neuroendocrine Tumor ◽

Predicting Factor

Abstract Background: Rectal neuroendocrine tumors (NET) <10 mm are typically treated with endoscopic resection, while those >20 mm should be treated with radical surgical resection. However, the proper treatment methodology for 10-20-mm sized rectal NETs remains controversial. The purpose of this study was to investigate the appropriate treatment strategy for 10-20-mm sized rectal NETs by verifying factors that can predict metastasis.Methods: A total of 24 patients with 10–20-mm sized NETs who were treated at Pusan National University Yangsan Hospital from January 2009 to September 2020 were included. The patients were divided into the metastasis and non-metastasis groups, and their respective data were analyzed.Results: Seven patients had metastasis (29.2%) while 17 patients had no metastasis (70.8%). The tumor size, based on the endorectal ultrasound (EUS) findings, was significantly larger in the metastatic than in the non-metastatic group (14.4 vs. 10.2 mm, p = 0.029); however, the pathological tumor size did not show significant differences (13.3 vs. 11.8 mm, p = 0.065). Lymph node enlargement was observed in a single patient (14.3%) in the metastatic group, based on EUS and computed tomography (CT) imaging findings. The mitotic count (p = 0.017) and Ki-67 index (p = 0.014) were significantly higher in the metastatic group than in the non-metastatic group. The two groups also showed a significant difference in the proportion of patients with tumor grade 2 (71.4% vs. 5.9%, p = 0.003). In multivariate analysis, the tumor grade was the only independent metastasis-predicting factor (odds ratio = 49.25; 95% confidence interval = 2.55–950.83; p = 0.010). Conclusions: Regarding the treatment of 10–20-mm sized rectal NETs, tumor grade 2 should be the most important factor to determine whether additional radical resection is necessary.

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Intralesional Zinc Sulfate 2% Vs Intralesional Vitamin D In The Treatment Of Planter Warts

QJM ◽

10.1093/qjmed/hcab093.016 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Fatma Saber

Keyword(s):

Vitamin D ◽

Zinc Sulfate ◽

Therapeutic Option ◽

Sulfate Solution ◽

University Hospital ◽

Response To Treatment ◽

Intralesional Injection ◽

Equal Chance ◽

Significant Difference ◽

Randomization Process

Abstract Background verrucae are benign proliferations seen in skin and mucosae due to infection with papillomaviruses. Aim and Objectives the aim of this work is to compare the clinical efficacy of intra-lesional 2% zinc sulfate solution vs intralesional vitamin D in the treatment of planter warts, Subjects and Methods this is Three armed single blinded randomized clinical trial included 105 patients presented with planter warts, Patients were all recruited from the Dermatology outpatient clinic at Ain-Shams University Hospital and Almateria hospital during the period From July 2018 to July 2019, Patients included in the present study were divided into 3 groups, 35 patients per group by simple randomization process which could allocate patients to either of three arms randomly and each patient would have an equal chance to be allocated to either of the three arms, Results There was no statistically significant difference between the 3 studied groups as regard the response to treatment after 1st, 2nd and 4th session. While after the 3rd session, there was statistically significant increase in the numbers of partial responders in the 3 studied groups (P = 0.023), Conclusion the current study showed that intralesional injection of 2% zinc sulfate is a better therapeutic option in the treatment of planter warts in comparison with intralesional vit D,

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1615: Testicular Maturation Arrest to Testis Cancer - is there a Spectrum of Expression of Vitamin D Receptors and a Role for Vitamin D Treatment

The Journal of Urology ◽

10.1016/s0022-5347(18)33807-2 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 520-521

Author(s):

Ajay K. Nangia ◽

Vince Memoli ◽

Alan Schned ◽

Oya Hill ◽

Catherine E. Schwender

Keyword(s):

Vitamin D ◽

Testis Cancer ◽

Maturation Arrest ◽

Vitamin D Receptors

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Potential predictive marker of treatment effectiveness in patients with osteopenic syndrome after surgical menopause

GYNECOLOGY ◽

10.26442/20795696.2020.4.200188 ◽

2020 ◽

Vol 22 (4) ◽

pp. 39-42

Author(s):

Yansiiat Z. Zaydieva ◽

Elena V. Kruchinina ◽

Olga S. Gorenkova ◽

Elena Yu. Polyakova ◽

Elena N. Kareva ◽

...

Keyword(s):

Vitamin D ◽

Combination Therapy ◽

Vitamin D Receptor ◽

Surrogate Marker ◽

Predictive Marker ◽

Expression Level ◽

Mineral Density ◽

Vitamin D Receptors ◽

Surgical Menopause

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy. Aim. To search a molecular predictive marker of the effectiveness of OS treatment. Materials and methods. The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood. Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy. Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

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