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Galectin-3 (Gal-3) regulates basic cellular functions such as cell-cell and cell-matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay.We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings.In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions.

The use of galectin-3 ThyroTest in the preoperative evaluation of cytologically indeterminate (Thy-3) thyroid nodules has been largely validated by retrospective and prospective multicentre studies. Here we report the results of galectin-3 ThyroTest routinely applied in the management of Thy-3 nodules in combination with clinical and ultrasonography (US) examination, in which galectin-3 positive nodules were directly referred to surgery whereas galectin-3 negative lesions were considered for clinical and US long-term follow-up. A cohort of 331 patients, bearing 340 thyroid Thy-3 nodules, was enrolled and subjected to galectin-3 expression analysis. A total of 256 galectin-3 negative nodules were directed to periodical clinical and US examination, while 84 galectin-3 positive cases were referred to surgery. Excluding 63 dropout patients plus 15 patients that were operated because of clinical reasons the remaining 176 galectin-3 negative nodules were followed with clinical and US examination for an average period of 31 months. During the follow-up, the volume of galectin-3 negative nodules was unchanged in 85 cases (48 %), reduced in 47 (27 %), and increased in 44 (25 %). Based on combined clinical features and US follow-up results, a total of 36 out of 191 galectin-3 negative nodules (19 %) were referred to surgery, with a final histological finding of 28 benign lesions, three follicular tumor of uncertain malignant potential (FT-UMP), and five malignant lesions, corresponding to a 7 % false negative rate. In the group of 84 galectin-3 positive nodules, we detected 65 thyroid cancers with a prevalence of 77 %, 12 FT-UMPs, and 7 false positive lesions, corresponding to a 4 % false positive rate. A total of 150 patients were not operated and are still under clinical and US monitoring while surgery was performed in 118 patients with a final 70 thyroid cancers diagnosed, corresponding to a 59 % prevalence of malignancy detected at surgery and to a 26 % prevalence of malignancy among the entire Thy-3 nodule population. Galectin-3 ThyroTest is an easy and cheap diagnostic procedure that integrates conventional fine-needle-aspiration cytology, reduces the number of unnecessary thyroidectomies and increases the rate of malignancy at surgery. Clinical and US follow-up of galectin-3 negative lesions allows to further reduce false negative cases.

In Western countries, breast cancer is the most common cancer in women, whereas metastases to the breast from extramammary malignancies are extremely rare. We present the case of a 60-year-old woman, who underwent surgery in 2007 for clear cell renal cell carcinoma and who 4 years later presented with a breast metastasis from clear cell renal cell carcinoma.

Background: Microtubules are involved in cell growth and division, motility, signalling and in the development and maintenance of cell shape. Consequently, the non-equilibrium dynamics of these microtubules can be crucial to cellular function, including cancer development. Although the involvement of tubulins in human development has been well investigated, the role of alpha- and beta-tubulins in human tumorigenesis still remains controversial. The aim of this study was to investigate alpha- and beta-tubulin protein expression in rectal cancer development., Patients and Methods: By immuno-histochemistry, using alpha- and beta-tubulin monoclonal antibodies, 66 patients were examined, 32 of whom (22 male, 10 female; range 31-60 years, mean age 49.5 years) had preneoplastic lesions discovered during endoscopic surveillance, which were classified as mild, moderate and severe dysplastic polyps of the rectum, and 34 had invasive adenocarcinomas (24 male, 10 female; range 39-60 years, mean 52 years) of the rectum, with no local or distant metastases at the time of surgical resection., Results: In preneoplastic lesions, no statistically significant relationship was found among alpha- and beta-tubulin protein expression, grade of dysplasia, or other clinical data. Statistical association among alpha- and beta-tubulin immunoreactivity and Dukes' stages B and C was found with p = 0.017 and p = 0.009, respectively. No statistical relationship was found between alpha- and beta-tubulin protein expression among different grades of dysplasia. On the contrary, a significant relationship was detected among tubulins in different stages of cancer., Conclusion: In this preliminary study a significant difference of alpha- and beta-tubulin protein expressions was found in polyps and invasive cancer of the rectum, indicating a possible role of tubulins in invasive, but not in preinvasive cancer development. This preliminary data suggest the possibility of performing alpha- and beta-tubulin protein expression in order to identify B stage versus C stage rectal cancer, before surgical treatment.

Recent technological advances have led to an increasing ability to detect isolated or groups of tumour cells in blood, lymph nodes or bone marrow in patients with different tumour types. However, the clinical evidence of these advances is unclear. The detection and the characterisation of circulating breast cancer cells and the eventually micrometastasis represent an important prognostic factor with therapeutic implications. The number of neoplastic cells being very small, these are not easily detected by using only cytomorphology, possibly associated to immunocytochemistry. In the last decade many studies have been directed in order to identify new assays. In the present review the Authors summarize advantages and disadvantages about two different technical approaches: molecular and immunomagnetic selection with cellular enrichment and immunocytochemistry.

The Authors highlight the efficacy of the Lauren's classification in 28 surgically treated gastric cancer patients. Lauren's classification allows a prognostic evaluation corresponding to the effective gastric cancer natural history. Present histo-morphological classification criteria appear not to coincide with the clinical evolution; as a matter of fact over- or understaging is possible in gastric cancer patients. 64,28% of the Lauren's classification intestinal type patients survive after a four year follow up vs. 42,85% of the diffuse type patients. The Authors discuss about new biomolecular knowledge in gastric cancer oncogenesis.

Purpose: The present study investigates the daily pattern of hunger sensation (HS), namely orexia, in patients affected by "Dysthymic Disorder" (DD). The aim is to detect whether there are changes in the circadian rhythm (CR) of HS, herein investigated as a "marker rhythm", that can reveal a dysfunction of the "circadian biological clock" (CBC). In such a circumstance, one could be authorised to suggest a resynchronizing therapy, via antidepressant chronizing drugs and/or morning exposure to bright light, as it is currently done in other types of human depression, having a documented dysfunction of the CBC., Materials and Methods: Volunteered with informed consent for the study 6 women (age = 34-56 years; mean BMI = 22.7 +/- 4.8 kg/m2) affected by DD. 10 clinically healthy women (CHW, age = 21-52 years; mean BMI = 24.0 +/- 0.5 kg/m2) were recruited as the controls. Both of the dysthymic patients (DP) and CHW were asked to compile the "orexigram", which was chronobiometrically analyzed by means of the 1. conventional statistical methods; 2. rhythmometric analysis for the CR; 3. spectral analysis for the harmonic components of the orexigram., Results: The DP were found to be characterized by a normal daily level of HS, with 1. the CR of the orectic stimulus to be preserved and well located in its acrophase, and 2. the spectrogram of the orexigram to be substantially well configured., Conclusions: The above-cited results suggest that the DP show no alterations in the HS marker rhythm that can be taken as an evidence for declaring that the DD is not characterized by a relevant dysfunction of the CBC. Lacking in particular a phase-shift in HS marker rhythm, it can be argued that the DD is an affective disorder for which a resynchronizing therapy (exposure to bright light or pharmacological chronizers) seems to be "a priori" not indicated.

This investigation deals with the circadian rhythm (CR) of hunger sensation (HS) in obese patients before and after a four-week, moderately hypocaloric diet with a substitutive meal. The study was performed on 25 non-diabetic obese patients (5 males and 20 females, mean age: 39.7 +/- 7, mean BMI: 27.9 1.4 Kg/m2), whose obesity was not associated with impaired glucose tolerance (IGT), binge eating, nor endocrine diseases. Their daily HS profile (orexigram) was analysed chronobiometrically. The moderately hypocaloric diet with a substitutive meal reduced the daily HS by about 10% by the fourth week. This reduction was apparently due to a tonic and amplitude modulation of the HS CR and was not accompanied by its disruption. No conclusions, however, could be drawn with regard to its orectic and clinical effects beyond four weeks.

Objective: The present study investigates the daily pattern of hunger sensation (HS) in women affected by "seasonal affective disorder--depression type" (SAD-DT), before and after therapeutic exposure to bright light (phototherapy). The aim is to detect whether there are disorders in daily HS during the active phase of the disease which can be normalized by an effective treatment of the depressive status, via phototherapy., Materials and Methods: Volunteered for the study 4 women affected by SAD-DT, 32-58 years old (BMI: 17.8-29.6 Kg/m2); 10 clinically healthy women (CHW), 21-52 years old (BMI: 23 e 25 Kg/m2) were recruited as controls. Both of the SAD-DT patients and CHW were asked to compile the "orexigram", which was chronobiometrically analyzed by means of the 1. conventional statistical methods; 2. rhythmometric analysis; 3. spectral analysis., Results: Before phototherapy, the SAD-DT patients were found to be characterized by an increased HS (hyperorexia), with the circadian rhythm of the orectic stimulus (OS) which is shifted in its acrophase, being prone to become "free running". After phototherapy, the SAD-DT patients were found to show a little insignificant decrease in their OS, which still maintains a delayed phase in its circadian rhythm as well as the tendency to be "free running"., Conclusions: The pre-treatment findings suggest that the SAD-DT patients are affected by hyperorexia associated with a "phase-shift" for the circadian periodicity of their HS, which is prone to the desynchronization. Such a dyschronism reinforces the hypothesis that the SAD-DT may be pathogenetically sustained by a mechanism of "phase-shift". The post-treatment findings suggest that both the hyperorexia and dyschronism of the orectic circadian rhythm are uncorrected by the phototherapy, even though the SAD-DT patients seem to have had beneficial antidepressive effects from the therapeutic intervention. The persisting dyschronism indicates that the photic stimulus is not able to completely reset the biological clock of the suprachiasmatic nuclei, at least for the phasic modulation of the HS circadian rhythm. The orexigram, thus, could be enclosed among the clinical tools in order to assess the complete efficacy of the phototherapy in SAD-DP patients.

Purpose: The present study is devoted to identify the normotensive subjects who are at a "presumptive risk" (PR) for hypertensive crisis, by applying the "fractal interpolation" (FI) to blood pressure 24-h pattern., Materials and Methods: The investigation was performed on 109 ascertained cases of normotension, who underwent a non-invasive ambulatory monitoring of their 24-h blood pressure, by applying the FI to their daily mean arterial pressure., Results: The study showed that the PR for hypertensive crisis can be found in 12% out of the investigated normotensives. The proportion of such a risk is not significantly higher in non-dippers as compared to dippers. Vice versa, the prevalence of cases with a PR for hypertensive crisis was found to be significantly increased in normotensives who were deprived by a significant blood pressure circadian rhythm as compared to those who showed the blood pressure circadian rhythm to be preserved. Furthermore, the cases "at risk" were found to show a different spectrum for the harmonic formants which compose the complex harmonic structure of the blood pressure 24-h variability., Conclusions: The PR for hypertensive crisis in normotensives seems to be increased by the loss of the blood pressure circadian rhythm, due to a change in the harmonic structure which confers the 24-h periodicity to the hemodynamic variable. This means that the abrogation of the blood pressure circadian rhythm in conditions of normotension promotes an adjunctive disorder for which the PR for hypertensive crisis is augmented.

Purpose: The present study applies the "fractal interpolation" (FI) to 24-h blood pressure nonivasively and ambulatorily monitored over a day-night period in secondary hypertensives. The purpose is the evaluation of the prevalence for a "presumptive risk" (PR) of hypertensive crisis., Materials and Methods: The study was carried out in 108 cases of secondary hypertension, who were non-invasively and ambulatorily monitored for their 24-h blood pressure values. The FI was applied to the time-qualified values of the mean arterial pressure., Results: The PR of hypertensive crisis was found in 11% of the investigated secondary hypertensive patients. Such a risk shows a not significant prevalence in dippers as compared to non-dippers, and in those who showed a significant blood pressure circadian rhythm as compared to those who showed the blood pressure circadian rhythm to be abolished. Additionally, a not significant difference was found between the cases "at risk" and "not at risk" as far as the spectrum of harmonic formants of the 24-h blood pressure pattern is concerned., Conclusions: The PR of hypertensive crisis is not associated with the dipping/non-dipping phenomenon as well as the circadian rhythmicity of blood pressure. Its occurrence in secondary hypertensives is essentially related to the disorder that is detectable in blood pressure non-linear variability. Therefore, such a risk may be caused by neurovegetative mechanisms which notoriously confer a non-linear chaotic variability to 24-h blood pressure pattern.

Purpose: The present study applies the "fractal interpolation" (FI) to blood pressure that was nonivasively and ambulatorily monitored over a day-night period in essential hypertensives. The purpose is the identification of cases who are at a "presumptive risk" (PR) for hypertensive crisis., Materials and Methods: The investigation was performed on 380 ascertained cases of essential hypertension, who underwent a non-invasive ambulatory monitoring of 24-h blood pressure. The FI was applied to the ambulatory mean arterial pressure., Results: The FI showed that the PR of hypertensive crisis can be found in 14% of the investigated essential hypertensive patients. Such a risk is not significantly higher in dippers as compared to non-dippers, and in those who showed a significant blood pressure circadian rhythm as compared to those who showed the blood pressure circadian rhythm to be abolished. Furthermore, no significant difference was found between the cases "at risk" and "not at risk" as far as the spectrum of harmonic formants of the 24-h blood pressure pattern is concerned., Conclusions: The PR of hypertensive crisis is not correlated to the dipping/nondipping condition, circadian rhythmicity and complex harmonic structure of 24-h blood pressure pattern. Its occurrence depends essentially from the disorder that is detectable in 24-h blood pressure pattern. Therefore, such a PR in essential hypertensives may be attributed to the mechanisms, likely neurovegetative, which confer a non-linear chaotic variability to 24-h blood pressure values.

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Hunger sensation (HS) is a signal whose levels change during the 24-h day. The daily mean level of HS was correlated with the human body compartments, as investigated by bioelectrical impedance analysis, to detect the relationship between the orectic perception and both the free fat mass (FFM) and the fat body mass (FBM) in 22 clinically healthy subjects (CHS) (2 M, 20 W, BMI: 18.5-24.0 kg/m2) and 48 obese patients (OP) (4 M, 44 W, BMI: 25.2-54.7 kg/m2). In CHS, the daily mean level of HS correlated positively with the FFM and negatively with the FBM. These correlations were not present in OP. This lack of relationships between HS and the body compartments where energy is maximally consumed (i.e., the FFM) and maximally stored (i.e., the FBM) indicates that the orectic response to energy expenditure and the orectic inhibition to fat accumulation are feedback mechanisms which are impaired in obesity.