Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic use of octreotide is restricted primarily to the management of acromegaly and neuroendocrine tumors, both of which are rare medical conditions. Similarly, chloroquine is used mainly for the treatment of malaria, which is designated as a rare disease in Western countries. This limited exploitation contradicts the experimental findings of numerous studies outlining the possible expansion of the use of octreotide to include the treatment of common human malignancies and the repositioning of chloroquine in oncology. Herein, we review the current knowledge on the antitumor function of these two agents stemming from preclinical or clinical experimentation. In addition, we present in silico evidence on octreotide potentially binding to multiple Wnt-pathway components. This will hopefully aid in the design of new efficacious anticancer therapeutic regimens with minimal toxicity, which represents an enormous unmet demand in oncology.

Marketed drugs used for the management of hypercholesterolemia as anticancer armament.

The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor-patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity. This review aims to present the anticancer properties of drugs used for the management of hypercholesterolemia. A global view of the antitumorigenicity of all marketed antihypercholesterolemic drugs is of major importance, given that atherosclerosis, which is etiologically linked to hypercholesterolemia, is a leading worldwide cause of morbidity and mortality, while hypercholesterolemia and tumorigenesis are known to be interrelated. In vitro, in vivo and clinical literature data accumulated so far outline the mechanistic basis of the antitumor function of these agents and how they could find application at the clinical setting.

Biochemical Effects of Levothyroxine Withdrawal in Patients with Differentiated Thyroid Cancer.

BACKGROUND: Patients with differentiated thyroid carcinoma (DTC) are submitted to withdrawal of levothyroxine (LT4) aftter thyroidectomy, in order to undergo radiodine ((131)I) treatment. PATIENTS AND METHODS: A total of 345 patients with a history of DTC were enrolled in the study. Their biochemical profile and serum free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH) levels were measured during withdrawal of LT4 treatment, and several months after restarting LT4. RESULTS: During withdrawal, the intra-individual percentage increase in total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and triglycerides was of the order of 60-80% and that for high density lipoprotein-cholesterol 30%. Creatinine increased by 30%, whereas Na and K levels decreased by 1%. The increase for creatine phosphate kinase was around 200-300%, for aspartate aminotransferase and alanine aminotransferase 50-80%, for γ-glutamyl transpeptidase 10-20%, and for lactate dehydrogenase 25%. Glucose decreased by 1-4%. CONCLUSION: Short-term, acute hypothyroidism in patients with DTC induces significant alterations in several biochemical parameters. The presence of other deteriorating diseases should be considered before submitting these patients to LT4 withdrawal.

Lower Levels of Vitamin D Among Bangladeshi Immigrants with Diabetes in Greece Compared to Indigenous Greek Patients with Diabetes.

AIM: Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences. We investigated a cohort of predominantly white Greek Caucasian and Bangladeshi immigrant patients with diabetes mellitus in order assess the association between diabetes mellitus and 25-hydroxyvitamin D [25(OH)VitD]. MATERIALS AND METHODS: A total of 165 patients from Bangladesh and 118 patients from Greece with diabetes were assessed for diabetes and 25(OH)VitD status. RESULTS: The 25(OH)VitD levels of Bangladeshi patients were significantly lower compared to Greek patients (12.42±5.86 ng/ml vs. 23.06±12.36 ng/ml, p<0.001). Only 1.2% of Bangladeshi patients vs. 24.57% of Greek patients had sufficient levels of 25(OH)VitD (≥30 ng/ml) CONCLUSION: The prevalence of vitamin D deficiency is very high amongst patients with diabetes but immigrants are at greater risk. Vitamin D supplementation could be valuable in the prevention or treatment of diabetes.

Primary thyroid lymphoma: The two ends of the spectrum.

We describe two different cases of prinary thyroid lymphoma (PTL). PTL is a rare malignancy. Nevertheless, it frequently presents diagnostic and therapeutic challenges. The first patient, a 79-year-old female, presented with a large, painless thyroid mass accompanied by severe obstructive symptoms of the upper respiratory and gastrointestinal track. The second patient (67-year-old female) presented with nodular goiter. Thyroidectomy - performed on the first patient for alleviation of obstructive symptoms - revealed the presence of a diffuse large B-cell lymphoma. Although she was administered standard chemotherapy she deceased four months later. In the second patient, primary thyroid lymphoma was an incidental finding following thyroidectomy performed for nodular goiter. These two cases illustrate the variable course of PTL, the possibility of which should be kept into consideration in clinical practice.

Association of Basal and Calcium-stimulated Calcitonin Levels with Pathological Findings After Total Thyroidectomy.

BACKGROUND/AIM: Medullary thyroid carcinoma (MTC) originates from thyroid C-cells and is a calcitonin-secreting tumor. Calcitonin is also elevated in C-cell hyperplasia (CCH). The objective of the study was to determine the optimal basal (bCT) and peak stimulated calcitonin (psCT) cut-off value for differentiating MTC from CCH, and to examine the histological findings of thyroidectomy in patients with maximum psCT >100 pg/ml. PATIENTS AND METHODS: Fifty-five patients had a maximum calcium-psCT >100 pg/ml and underwent total thyroidectomy. RESULTS: A total of 20 patients were diagnosed with MTC and the remaining 35 with CCH. A bCT level >17.4 pg/ml and psCT level >452 pg/ml demonstrated the best sensitivity and positive predictive value for differenting MTC from CCH. CONCLUSION: The overlap of calcitonin levels between MTC and CCH reduces the accuracy of the calcium stimulation test. Remarkably, an appreciable number of patients with psCT levels >100 pg/ml harbor differentiated thyroid carcinoma of follicular origin.

Seasonal variation of serum vitamin D among Greek female patients with osteoporosis.

BACKGROUND/AIM: Vitamin D (vitD) levels are positively associated with bone health and seasonality affects serum vit D. The aim of the study was to investigate the degree of seasonal variation on 25-hydroxyvitamin D (25(OH)D) serum levels in a population-based cohort of post-menopausal women with osteoporosis. PATIENTS AND METHODS: Serum levels of 25(OH)D were assessed in 596 patients (mean age=65.3 years; standard deviation (SD)=9.4) in different time points over a period of 2.5 years. RESULTS: The minimum 25(OH)D serum levels were observed in March (13.4±9.5 ng/ml) and the maximum levels in August, September and October (29.1±16.1, 28.9±12 and 28.4±8.9 ng/ml, respectively). The prevalence of vitD deficiency, insufficiency and sufficiency in March was 76.5, 15.7 and 7.8%, respectively. On the contrary, the highest prevalence of vitD sufficiency was observed in August, September and October (38.1%, 45.3% and 46.5%, respectively). CONCLUSION: Seasonal variations should be considered when measuring for 25(OH)D serum levels and treating vitD deficiency.