Browsing by Author "Mariash, Cary"

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    Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice
    (Springer Nature, 2013-09-13) Siddiqui, Rafat A.; Harvey, Kevin A.; Walker, Candace; Altenburg, Jeffrey; Xu, Zhidong; Terry, Colin; Camarillo, Ignacio; Jones-Hall, Yava; Mariash, Cary; Medicine, School of Medicine
    Background: The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice. Methods: We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean ± SD and analyzed with one-way ANOVA and Tukey's post hoc procedure. Results: Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of "PAM50" genes in the SK-BR-3 cell line from an ER⁻/Her-2⁺ to that resembling a "normal-like" phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin. Conclusions: The SK-BR-3 cells and DMBA-induced tumors, both with an ER⁻ and Her-2⁺ phenotype, were affected by the synergistic interaction of DHA and CCM. This suggests that the specific breast cancer phenotype is an important factor for predicting efficacy of these nutraceuticals. The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon the molecular phenotype of the cancer.
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    COVID-19-Induced Graves' Disease
    (Springer Nature, 2022-02-15) Ghareebian, Hagop; Mariash, Cary; Medicine, School of Medicine
    COVID-19, a multi-system disease, could potentially play a role in thyroid dysfunction. New reports show a prevalence of COVID-related thyroiditis. Recent studies suggest that there may be a higher risk of thyroiditis in the setting of SARS-CoV-2, and several cases of Graves’ disease have been reported in individuals with SARS-CoV-2, although the incidence of such findings and their relationship to COVID-19 is unknown. In this report, we present Graves’ hyperthyroidism in a 48-year-old African American male who was admitted to the hospital for complaints of cough, fatigue, and palpitations. He tested positive for SARS-CoV-2 and was found to have suppressed thyroid-stimulating hormone (TSH) and an elevated free T4. The patient had no prior history of thyroid disease. Initially, it was thought to be a case of viral thyroiditis, and he was discharged on prednisone. However, he was found to have positive thyroid-stimulating immunoglobulin (TSI) and a diffuse increase in flow on doppler ultrasound of the thyroid. Subsequently, he was started on anti-thyroid medications with significant improvement. What is unique about this case is that, unlike other described cases in the literature where there was a relapse of a known Graves' disease after COVID-19 disease, our patient did not have a history or symptoms of thyroid disease prior to this event, which should raise the concern about possible activation of Graves' disease after SARS-CoV-2 infection through an autoimmune pathway. In our opinion, physicians, particularly endocrinologists, must be aware of this condition and keep it in mind as a potential differential diagnosis when encountering a similar clinical scenario.
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    Dual Heterozygous Mutations in CYP21A2 and CYP11B1 in a Case of Nonclassic Congenital Adrenal Hyperplasia
    (Elsevier, 2022-10-21) Frontera, Eric D.; Brown, Joshua J.; Ghareebian, Hagop; Mariash, Cary; Medicine, School of Medicine
    Background/objective: Nonclassic congenital adrenal hyperplasia (NCCAH) may be overlooked or mistaken for polycystic ovarian syndrome. Unlike congenital adrenal hyperplasia (CAH), the enzymatic activities of 21-hydroxylase or 11β-hydroxylase in NCCAH are not completely lost. In this case, NCCAH presented in a patient with CYP21A2 and CYP11B1 heterozygous mutations, one of which is a variant of unknown significance in CYP11B1. Case report: A 30-year-old woman presented with a chief complaint of irregular menses and hirsutism. Previous medical history was significant for a prolactin level of 34.7 ng/mL (reference range, 2.0-23.0 ng/mL), a total serum testosterone level of 77 ng/dL (reference range, 25-125 ng/dL, not sex-specific), and a 2-mm × 3-mm pituitary lesion. An adrenocorticotrophic hormone stimulation test increased the 17-hydroxyprogesterone level from 444 ng/dL at baseline to 837 ng/dL at 60 minutes (baseline female reference range and stimulated reference ranges are 10-300 ng/dL and <1000 ng/dL, respectively). Gene sequencing revealed a heterozygous pathogenic CYP21A2 variant and a heterozygous, previously undescribed variant of unknown significance in CYP11B1. Discussion: Unlike CAH, NCCAH presents more subtly and later in life, and salt wasting and hypertension are not typically seen. Although mutations in CYP11B1 that cause steroid 11β-hydroxylase deficiency more commonly lead to the CAH phenotype, cases have been reported of CYP11B1 mutations leading to NCCAH, depending on the location of the mutations. Conclusion: This patient's case demonstrates physical examination and laboratory findings suggestive of NCCAH. Our case adds to the database of described mutations in CYP11B1 and suggests that heterozygous mutations in 2 different genes may present phenotypically as NCCAH.
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    SAT-495 1-α-Hydroxylase Activity-Mediated Hypercalcemia Associated with Ovarian Dysgerminoma
    (Oxford University Press, 2019-04-15) Subbu, Karthik; Saeed, Zeb; Mariash, Cary; Graduate Medical Education, IU School of Medicine
    Background: Humoral hypercalcemia of malignancy is classically associated with increased tumor production of parathyroid hormone-related peptide (PTHrP). While 1,25 dihydroxy vitamin D (1,25D) mediated hypercalcemia has been demonstrated with a range of granulomatous disorders and lymphomas, there have only been 11 cases reported in ovarian dysgerminomas, of which only 2 were in adults. Ovarian dysgerminoma is the most common ovarian malignancy in childhood but is much more infrequent in adults. We present a case of a rare ovarian malignancy in an adult woman with an even more rare presentation of 1,25D mediated hypercalcemia. Case: A 23 year old African American female with a history of intravenous drug abuse was admitted for dilation and curettage for suspected molar pregnancy. Her operative course was complicated by uterine perforation requiring diagnostic laparoscopy which revealed a large, firm, irregular left ovarian mass concerning for malignancy. Laboratory findings were pertinent for calcium 13.4mg/dl (8.5-10.5), albumin 3.5g/dl (3.5-5.0), creatinine 1.61mg/dl (0.6-1.2), phosphorus 4.0mg/dl (2.5-4.5), alkaline phosphatase elevated at 170 Units/L (25-125) and appropriately suppressed PTH of 4 pg/ml (10-65). Previous calcium levels were all normal. Additional work-up revealed normal PTHrP, 25-OH Vitamin D 14.2 mg/dl (20-50) and high-normal 1,25 dihydroxy vitamin D at 76pg/ml (19.9-79.3). Tumor markers β-hCG, LDH, α-fetoprotein, and CA 19-9 were all elevated. CT scan of the abdomen and pelvis characterized the lesion to be a heterogenous 16.5 x 10.0 x 18.3 cm pelvic mass. The patient was initially given intravenous isotonic fluids and 4mg of intravenous zoledronic acid which decreased calcium to 10mg/dl. Biopsy of the mass performed during initial laparoscopy confirmed the suspected diagnosis of ovarian dysgerminoma. A left salpingo-oophorectomy was performed and the patient developed mild hypocalcemia post-operatively to a nadir of 6.7mg/dl (adjusted for albumin: 7.7) requiring calcium supplementation. The 1,25D level on post-operative day 2 was low at 9.1 pg/ml. Surgical pathology demonstrated metastatic ovarian dysgerminoma with para-aortic lymph node involvement. Conclusion: Our case demonstrates an unusual case of humoral hypercalcemia of malignancy. Exogenous 1-α-hydroxylase expression has been reported exceedingly rarely in solid tumors other than lymphomas. While we were unable to stain the tumor for 1-α-hydroxylase, the abrupt drop in 1,25D and calcium levels post resection strongly support our diagnosis. To our knowledge, our patient is the second oldest patient reported in literature to have 1,25D mediated hypercalcemia associated with an ovarian dysgerminoma.