Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma.

Lessons Learned: Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

Background: Current data support the possibility of antitumor activity of melatonin and metformin.

[Family diabetes and main noncommunicable diseases: The described and potential effect of metformin (remembering Vladimir Dilman).].

The work discusses the two biomedical problems: family diabetes (bearing in mind the presence of cases of type 2 diabetes mellitus in the family, including its different generations) and the features of relationship of family diabetes with major non-communicable human diseases (NCDs). The paper is timed to the anniversary of the famous - in our country and abroad - expert in the field of gerontology and endocrinology, Professor V.M.

Upregulation of Akt/Raptor signaling is associated with rapamycin resistance of breast cancer cells.

mTOR inhibitors are considered today to be one of the most promising anticancer drugs. Here to study the mechanism of the acquired resistance of MCF-7 breast cancer cells to mTOR inhibitors two different models of the cell resistance were used: rapamycin-resistant MCF-7/Rap subline developed under long-term rapamycin treatment, and metformin-resistant MCF-7/M subline obtained by long-term metformin treatment. We have found that both resistant sublines were characterized by common features: increased expression of mTOR-interacting Raptor protein, increased phosphorylation of Akt, and activation of growth-related transcriptional factor AP-1.

Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways.

The phenomenon of the primary or acquired resistance of cancer cells to antitumor drugs is among the key problems of oncology. For breast cancer, the phenomenon of the resistance to hormonal or target therapy may be based on the numerous mechanisms including the loss or mutation of estrogen receptor, alterations of antiapoptotic pathways, overexpression of growth-related signaling proteins, etc. The perspective approaches for overcoming the resistance may be based on the usage of compounds such as inhibitors of the cell energetic metabolism.

Dissimilar associations of same metabolic parameters with main chronic noncommunicable diseases (cancer vs some other NCDs).

Hormone-dependent tissues' cancers (mainly breast and endometrial and several others) are among the most frequent malignancies in adults and are often discussed in context of their correlation with other chronic noncommunicable diseases (NCDs), for example, cardiovascular and cerebrovascular conditions, and their risk factors, which may also be hormone metabolic. An idea that is often expressed delineates common factors leading to NCDs of malignant and nonmalignant nature. However, this idea is not always confirmed by study results.

Endocrinology of obese and nonobese endometrial cancer patients: is there role of tumor molecular-biological type?

To compare endocrine characteristics of  endometrial cancer (EC) patients based on recent molecular EC types classification.  A total of 234 treatment-naive EC patients as well their tumors were studied. Patients with mutations demonstrated tendency to lower body mass index (BMI) and higher serum estradiol.

Endometrial cancer evolution: new molecular-biologic types and hormonal-metabolic shifts.

The question hidden in the title of this manuscript (whether the topic develops or remains constant) is important for all areas of science. It is also a serious problem for endometrial cancer (EC) study. In recent times the incidence of EC gradually increases in parallel with obesity epidemics.

[Endocrinology of cancer and age: early and late stages of ontogenesis].

Processes important for hormone-mediated carcinogenesis are present on different, even very early, ontogenesis stages. Early shifts in hormone-metabolic status often display opposite correlations with the risk of most common age-associated non-communicable pathologies (namely, hormone-dependent cancers and cardiovascular diseases). Additional known contradiction is the raise of reproductive system tumors incidence in the age associated with lower production of mitogenic hormones.

Features of endometrial cancer in patients with 'metabolically healthy' versus 'standard' obesity: the decreasing frequency of metabolically healthy obesity.

Background: As endometrial cancer (EC) prevalence increases with obesity, we aimed to determine whether EC characteristics depend upon obesity type: 'standard' (SO) or 'metabolically healthy obesity' (MHO).

Patients & Methods: 258 EC patients were included. Data on anthropometry, blood hormones, lipids and glucose, and tumor features were collected.

Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases.

The changes in the brain signaling systems play an important role in etiology and pathogenesis of Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), being a possible cause of these diseases. Therefore, their restoration at the early stages of T2DM and MS can be regarded as a promising way to treat and prevent these diseases and their complications. The data on the functional state of the brain signaling systems regulated by insulin, IGF-1, leptin, dopamine, serotonin, melanocortins and glucagon-like peptide-1, in T2DM and MS, are analyzed.

Features of omental adipose tissue in endometrial cancer patients with 'standard' or 'metabolically healthy' obesity: associations with tumor process characteristics.

Purpose: Adipose tissue products may contribute to endometrial cancer (EC) initiation and further growth that encourages the analysis of this issue in patients with different obesity phenotypes.

Methods/patients: Omental fat depot characteristics were studied in EC patients (n = 57) with "standard" (SO) or "metabolically healthy" (MHO) obesity. Collected omental samples were evaluated by immunohistochemistry /IHC/ for brown fat marker UCP1, CYP19 (aromatase) and macrophage infiltration markers (CD68, CD163, crown-like structures/CLS) expression.

Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer.

Thyroid cancer (TC) is the most common endocrine malignancy and its incidence has increased over the last few decades. As has been revealed by a number of studies, TC tissue's micro-RNA (miRNA) profile may reflect histological features and the clinical behavior of tumor. However, alteration of the miRNA profile of plasma exosomes associated with TC development has to date not been explored.

Serum Levels of 8-Hydroxy-2'-Deoxyguanosine DNA in Patients with Breast Cancer and Endometrial Cancer with and without Diabetes Mellitus.

Blood levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured by enzyme immunoassay after overnight fasting in untreated breast cancer and endometrial cancer patients (N=170) of mainly postmenopausal age with and without type 2 diabetes mellitus. The concentrations of 8-OHdG in patients with breast cancer were higher than in patients with endometrial cancer and in patients with breast cancer and diabetes in comparison with patients with breast cancer without diabetes. No correlations of blood 8-OHdG levels with glycemia, age, and clinical stage of disease were detected.

The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling.

Metformin, a biguanide antidiabetic drug, is used to decrease hyperglycemia in patients with type 2 diabetes. Recently, the epidemiological studies revealed the potential of metformin as an anti-tumor drug for several types of cancer, including breast cancer. Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways.

[Pre-surgical hormonal-metabolic state in endometrial cancer patients who underwent laparoscopy or laparotomy].

73 randomly selected from the entire array menopausal endometrial cancer patients (34 of whom were subjected to further surgery by laparotomy and 39 - by laparoscopic ap- proach) were examined 48-72 hours before surgery. Patients passed anthropometry, their medical history was collected, and in the blood serum, taken on an empty stomach, glucose, gly- cated hemoglobin, lipid fractions, insulin, thyrotropin, estradiol and testosterone levels were measured while insulin resistance index was calculated. Although patients who later went through laparoscopic surgery were characterized by somewhat higher body mass and waist circumference, other investigated pa- rameters did not differ between laparoscopy and laparotomy groups.

[The role of inflammatory and anti- inflammatory factors in endometrial cancer and its types: tumor and adipose tissue].

An inflammation expressed in a moderate degree and hav- ing a chronic character is associated with the local changes in the tumor and adipose tissue (manifested, in particular, by lym- phocytic and macrophage infiltration) as well as with systemic shifts involving hormone and hormone-like elements for their implementation. The unfavorable consequences of these shifts may be restrained due to the endogenous anti-inflammatory re- serves (systems) and intentionally used exogenous agents with the same action. These issues are considered on the example of endometrial cancer, for the occurrence and course of which a considerable significance is attributed to the excess of body fat, especially in its <>, rather than <> variant.

[The first results of assessment of clinical efficacy of melatonin and metformin in patients with disseminated skin melanoma receiving dacarbazine as first-line systemic therapy].

The aim of the study was to assess efficacy and safety of combined therapy with dacarbazine and melatonin or metformin in comparison with dacarbazine alone in the 1st line of therapy of cutaneous melanoma. Thirty-six patients with disseminated melanoma, therapy naïve, were included between March 2014 and December 2015. Patients received DTIC 1000 mg/m2 in day 1 of 28-day cycle either as monotherapy (group 1) or in combination with melatonin 3 mg PO daily (group 2) or metformin 850 mg 2 times a day PO daily (group 3).

[Oncoendocrinology: interim results and new challenges].

Over the few past years there have been passed many significant and positive changes in various fields of oncology due to both the use of achievements, stimulated by previous generations, and the progress of modern technology. This largely concerns endocrinology of malignant tumors, which is reflected in this article on the basis of the experience of the N.N.

[Hormone-associated properties and plasticity of omental fat: the relation with clinical-morphological features of endometrial cancer in patients with different obesity phenotypes].

The authors aimed to compare expression of UCP1, aromatase (CYP19), markers of macrophage infiltration (CD68, CD163), omentin and PTEN in omental fat of endometrioid or non-endometrioid endometrial cancer (EC) patients with signs of standard (SO) or metabolically healthy obesity (MHO) by immunohistochemical (IHC) or real-time PCR methods. Totally 57 omental fat samples collected during surgery in EC pts (average age 60.1) were studied.