Hereditary breast and ovarian cancer: from genes to molecular targeted therapies.

Hereditary familial tumors constitute 10-15% of all malignancies and present opportunities for the identification of therapeutic approaches against specific germline genetic defects. Hereditary breast and ovarian cancer (HBOC) syndrome, which is linked to the pathogenic mutations of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes, is an important research model for personalized therapeutic approaches for specific germline mutations. HBOC is characterized by multiple cases of breast and ovarian carcinoma in association with other tumors (prostate, pancreas and stomach carcinoma) within the same family branch, a young age of onset (<36 years), bilaterality and an autosomal dominant pattern of inheritance. Counseling, evaluation of the clinical criteria for the diagnosis of HBOC, and the performance of genetic testing allow for the identification of subjects with BRCA1/2 mutations and provide crucial information for clinical and therapeutic management. The identification of a BRCA gene mutation has therapeutic implications for women with metastatic and non-metastatic breast cancer. In the therapeutic setting of BRCA+ breast cancer, treatment with poly (ADP-ribose) polymerase (PARP) inhibitors, which keep cancer cells from repairing their damaged DNA and cause cell death, is remarkable. This review summarizes the evidence demonstrating the value of BRCA1/2 status as a diagnostic and prognostic tool and as a predictive biomarker in the personalized approach to hereditary BRCA + cancers.

A Proteomic Analysis of Discolored Tooth Surfaces after the Use of 0.12% Chlorhexidine (CHX) Mouthwash and CHX Provided with an Anti-Discoloration System (ADS).

Chlorhexidine (CHX) is considered the gold standard for the chemical control of bacterial plaque and is often used after surgical treatment. However, CHX employment over an extended time is responsible for side effects such as the appearance of pigmentations on the teeth and tongue; the discoloration effects are less pronounced when using a CHX-based mouthwash with added an anti-discoloration system (ADS). The aim of this study was to evaluate, using one- and two-dimensional gel electrophoresis combined with mass spectrometry, the possible proteomic changes induced by CHX and CHX+ADS in the supragingival dental sites susceptible to a discoloration effect. The tooth surface collected material (TSCM) was obtained by curettage after resective bone surgery from three groups of patients following a supportive therapy protocol in which a mechanical control was combined with placebo rinses or CHX or a CHX+ADS mouthwash. The proteomic analysis was performed before surgery (basal conditions) and four weeks after surgery when CHX was used (or not) as chemical plaque control. Changes in the TSCM proteome were only revealed following CHX treatment: glycolytic enzymes, molecular chaperones and elongation factors were identified as more expressed. These changes were not detected after CHX+ADS treatment. An ADS could directly limit TSCM forming and also the CHX antiseptic effect reduces its ability to alter bacterial cell permeability. However, Maillard's reaction produces high molecular weight molecules that change the surface properties and could facilitate bacterial adhesion.

Assessing Biocompatibility of Face Mask Materials during COVID-19 Pandemic by a Rapid Multi-Assays Strategy.

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.

Influence of Tooth-Brushing on Early Healing after Access Flap Surgery: A Randomized Controlled Preliminary Study.

In the present study, the clinical outcomes obtained using three different protocols of post-operative plaque control for the 4 weeks after surgery were compared. Thirty healthy subjects, presenting at least one periodontal pocket requiring resective surgery, were selected and randomly distributed to three different groups corresponding to respective post-surgical protocols: (A) toothbrushes + chlorhexidine + anti-discoloration system (ADS + CHX); (B) toothbrushes + chlorhexidine (CHX); (C) only toothbrushes. The full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing pocket depth (PPD), recession depth (REC), clinical attachment level (CAL), and bleeding on probing (BoP) were measured in six aspects per tooth (mesio-buccal (MB), buccal (B), disto-buccal (DB), disto-lingual (DL), lingual (L), and mesio-lingual (ML)) at baseline, 3 months, and 6 months after surgery. FMPS and FMBS did not significantly change (p > 0.05), whereas PPD and CAL significantly decreased, and REC significantly increased in all groups during the study (p < 0.05). Clinical results were satisfactory in all cases, with no significant differences between groups 3 months after surgery. Six months after surgery, only PPD-MB was significantly different in the three groups (p < 0.05). Nevertheless, this value was not clinically relevant because the value of PPD-B (about 2 mm) in group C was physiologic. The mechanical plaque control was proven to be fundamental and sufficient in all the six aspects per tooth to guarantee an excellent clinical outcome without the need of chemical plaque control.

Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study.

BACKGROUND: Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. METHODS: Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. RESULTS: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student's t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). CONCLUSION: Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.

Urinary proteomic profiles of prostate cancer with different risk of progression and correlation with histopathological features.

Prostate cancer (PCa) is the most common tumor in men with extremely variable outcome, varying from latent or indolent form to very aggressive behavior. High grade tumors, expansions exceeding the prostatic capsule into the surrounding soft tissues and spreading through lymph vascular channels, represent the most consistent unfavorable prognostic factors. However, accuracy in the prediction of the disease progression is sometimes difficult. Along with new molecular diagnostic techniques and more accurate histopathological approaches, proteomic studies challenge to identify potential biomarkers predictive of PCa progression. In our study we analyzed the urinary proteomes of 42 patients affected by PCa through two-dimensional electrophoresis associated with mass spectrometry. Proteomic profiles were correlated to histopathological features including pTNM stage and tumor differentiation in order to provide new promising markers able to define more accurately the PCa aggressiveness and driving new therapeutic approaches.

Liquid biopsy with cell free DNA: new horizons for prostate cancer.

Although prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years. Due to the high variability of the scientific methods adopted and a lack of standardized median cfDNA levels, results fluctuate across different studies. These differences may be due to the cfDNA source, the quantification method, or the fragmentation pattern. Blood plasma is the most frequently analyzed biological fluid, but seminal plasma has been reported to contain higher cfDNA concentration due to its vicinity to the tumor origin. CfDNA has been shown to be composed of single-stranded (ssDNA) and double-stranded DNA (dsDNA), so the total cfDNA concentration should be preferred as it corresponds best to the tumor mass. Fluorometry and capillary electrophoresis (CE) may be quick and cost-effective tools for cfDNA assessment in a clinical setting. The greatest future challenge is the elaboration of common guidelines and standardized procedures for diagnostic laboratories performing cfDNA analysis. A multiparametric approach combining the analysis of total cfDNA (both ssDNA and dsDNA), cfDNA fragment length, and specific genetic mutations (ctDNA assessment) is required for optimal future applications of liquid biopsy.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study.

BACKGROUND: Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30). METHODS: Participants were women with migraine afferent to a headache centre; controls were female patients' acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS. RESULTS: In menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than in the respective control groups (fertile age and post-menopause) (p < 0.001, one-way analysis of variance followed by Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/3 months (p ≤ 0.005, linear regression analysis). CONCLUSION: Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.

Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response.

In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD-1 treatments. The therapeutic response of patients was also retrospectively assessed. The cohort of the current study included 14 patients with advanced MM that had received anti PD-1 from January 2014 to December 2016 (12 males, 2 females; average age, 71 years; age range, 47-88 years). IHC analysis of MLH1, PMS2, MSH2 and MSH6 proteins was performed on paraffin-embedded primary tumor samples from each patient and on the 23 available metastasis specimens obtained from the Division of Pathology (University of Modena and Reggio Emilia). The results revealed that 7% of the primary melanoma tissue obtained from the patient cohort exhibited the loss of expression of at least one MMR protein. Three samples from one patient, including one primary melanoma and two metastases, exhibited no MSH6 expression and had the most successful response to anti PD-1 treatment, with a progression-free survival and overall survival of 956 and 2,546 days, respectively. In conclusion, the assessment of MMR protein expression represents a potential predictive marker that may have critical importance for patients with primary and metastatic MM, primarily as criterion for the adoption of immunotherapy treatments.

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis.

BACKGROUND: Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis. METHODS: Thirty patients with histologically proven PCa, 33 with benign prostate hyperplasia (BPH) and 21 healthy controls were enrolled. cfDNA was extracted from seminal fluid samples. cfDNA quantification and analysis were performed using Qubit ssDNA Kit and Agilent 2100 Bioanalyzer. Statistical analysis included: Levene's test, Shapiro-Wilk, Kolmogorov-Smirnov and Kruskal Wallis tests. RESULTS: Median cfDNA was significantly higher in PCa patients 428.45 ng/mL (173.93-1159.62) compared to BPH patients 77.4 ng/mL (18.23-501) and healthy controls 25.4 ng/mL (15.37-76.62). scfDNA fragments longer than 1000 base-pairs were more common in patients with PCa compared to those with BPH and controls. CONCLUSIONS: scfDNA concentration and fragment size differed significantly in the three groups of PCa, BPH and healthy controls. Both parameters are potential clinical biomarkers for PCa and can be used in both early diagnosis and follow-up. Using automated systems for high-throughput cfDNA quantification could improve the reproducibility of the method and facilitate the implementation of liquid biopsies in the clinical setting.

Evaluation of potential cardiovascular risk protein biomarkers in high severity restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder that, in case of severe symptoms, can be very distressing and negatively interfere with quality of life. Moreover, increasing evidences associate RLS with higher risk of cerebrovascular and cardiovascular disease (CVD). The purpose of this study was to quantify two proteins, previously identified by proteomics and potentially linked with CVD risk, namely kininogen-1 (KNG1) and alpha-1-antitrypsin (A1AT), in primary RLS patients at high severity grade (HS-RLS) in comparison to healthy control subjects. Proteins were quantified through enzyme-linked immunosorbent assay (ELISA) in plasma samples from 14 HS-RLS patients and 15 control individuals. The two groups were closely matched for age and gender. The expression level of KNG1 resulted significantly higher (p < 0.001), while A1AT was significantly decreased (p < 0.05) in HS-RLS patients compared to controls, confirming the relationship between these proteins and the disease severity. Furthermore, in patients group the association between the protein concentrations and the following parameters was further evaluated: age, disease onset and diagnosis, scores obtained from the RLS rating scales (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory) and smoking habit. All the considered variables resulted independent of protein levels, so the disease can be reasonably considered the main cause of protein changes. As emerged from the literature, high levels of KNG1 and low amounts of A1AT seem to be related with a highest probability to develop CVD. Consequently, these proteins may be reliable candidate biomarkers of CVD risk in patients with RLS at high severity grade.

Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology.

Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the bloodstream, hampering diagnosis through standard liquid biopsy procedures. Several tumors, as such as brain, kidney, prostate, and thyroid cancer, are in direct contact with other body fluids and may be alternative sources for cfDNA and ctDNA. Non-blood sources of cfDNA/ctDNA useful as novel oncologic biomarkers include cerebrospinal fluids, urine, sputum, saliva, pleural effusion, stool and seminal fluid. Seminal plasma cfDNA, which can be analyzed with cost-effective procedures, may provide powerful information capable to revolutionize prostate cancer (PCa) patient diagnosis and management. In the near future, cfDNA analysis from non-blood biological liquids will become routine clinical practice for cancer patient diagnosis and management.

Seminal Cell Free DNA Concentration Levels Discriminate Between Prostate Cancer and Benign Prostatic Hyperplasia.

BACKGROUND/AIM: Seminal plasma cfDNA (scfDNA) was recently proposed as a novel PCa biomarker. Our aim was to evaluate whether scfDNA could discriminate PCa from benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: A cohort of 43 patients (18 and 25 pathology proven PCa and BPH patients), and 13 healthy age-matched control subjects were enrolled. scfDNA quantification was performed. Data were analyzed through ANOVA testing. RESULTS: Average scfDNA concentrations were 1,407.83 ng/µl, 128.13 ng/µl and 78.09 ng/µl for PCa patients, BPH patients and healthy subjects, respectively. Statistical analysis showed a significant difference among the groups, allowing for distinction of patients with optimal accuracy. A cut-off level of 450 ng/µl scfDNA was identified for the differentiation of PCa and BPH patients. CONCLUSION: scfDNA concentrations are significantly different between PCa patients and BPH patients. scfDNA is a promising biomarker with several applications in PCa diagnosis, screening programs and therapeutic monitoring.

Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker.

Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed. To discover a novel, sensitive, non-invasive biomarker of prostate cancer, through the fluorometric quantification and the electrophoretic analysis of seminal cfDNA in prostate cancer patients compared to healthy individuals. The concentration of seminal plasma cfDNA in prostate cancer patients was 2243.67 ± 1758 ng/µl, compared to 57.7 ± 4.8 ng/µl in healthy individuals (p < 0.05). Electrophoresis sites distribution patterns were different; ladder fragmentation was associated with prostate cancer patients and apoptotic electrophoretic fragmentation with healthy individuals. Human seminal fluid can be a valuable source of cfDNA in the setting of liquid biopsy procedures for the identification of novel oncological biomarkers. Seminal plasma cfDNA in prostate cancer patients is significantly more concentrated than that of age-matched, healthy controls. Fluorometric measurement and electrophoretic assessment allow a reliable quantification and characterization of seminal plasma cfDNA, which can be used routinely in prostate cancer screening programs.

The value of fluorimetry (Qubit) and spectrophotometry (NanoDrop) in the quantification of cell-free DNA (cfDNA) in malignant melanoma and prostate cancer patients.

BACKGROUND: Circulating cell-free tumor DNA (cfDNA) is of crucial interest in oncology. cfDNA constitutes a potential prognostic and therapeutic marker for different solid tumors and can be used in the diagnostic and therapeutic management of cancer patients for which nowadays there are no valid laboratory markers. In the present study, the quality and quantity of the cfDNA were assessed by different quantification procedures, in order to identify the potential applications of these techniques in the preliminary cfDNA quantification. METHODS: Qubit with single (ss) and double strand (ds) DNA assay kits, NanoDrop and quantitative Real Time PCR (qPCR), were adopted to assess the cfDNA in the blood samples of 18 melanoma patients, 67 prostate cancer patients and 15 healthy controls. RESULTS: The quantification by NanoDrop (average value 8.48ng/µl, 95% confidence limit (CL)=7.23-9.73), Qubit ssDNA (average value 23.08ng/µl, CL=19.88-26.28), dsDNA (average value 4.32ng/µl, CL=3.52-5.12) assay kits and qPCR (average value 0.39ng/µl, CL=0.31-0.47) revealed differences among the four procedures. Qubit 2.0 ss-DNA kit gave higher cfDNA concentration values for all the samples analyzed. In detail, Qubit ssDNA assay revealed higher sensitivity in the quantification of small amounts of pure ss-DNA and ds-DNA, while NanoDrop allowed the assessment of the purity of cfDNA samples. CONCLUSIONS: The NanoDrop and Qubit 2.0 measurements were analyzed in order to define their correlation with qPCR cfDNA assessment, showing good correlation values with the qPCR that should be considered the "gold standard". In our proposal, the sequential combination of NanoDrop and Qubit ssDNA methods should be adopted for a cost-effective preliminary assessment of total circulating cfDNA in melanoma and prostate cancer patients, and only discordant values should undergo qPCR assessment.

PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

BACKGROUND/AIM: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. MATERIALS AND METHODS: In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. RESULTS: Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. CONCLUSION: NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies.

BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival.

BACKGROUND/AIM: The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management. PATIENTS AND METHODS: Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution. RESULTS: BRAF-mutated melanoma patients were the most common, representing 70% of the study population, while NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively. BRAF-mutated melanomas were mostly located at sites of intermittent sun exposure, and were associated with higher Breslow thickness and an increased number of mitosis. NRAS mutated melanoma were mainly observed in chronic sun-damaged areas and had a negative prognostic value, with shorter time to progression and a high incidence of central nervous system involvement. C-KIT mutated melanoma were located at acral and mucosal sites. Overall survival observed in the three groups of patients revealed wide differences. CONCLUSION: BRAF, NRAS and C-KIT melanomas constitute distinct clinico-pathological entities. BRAF-mutated melanoma benefit from both anti-BRAF and anti-MEK targeted therapies while triple-negative melanomas could benefit from novel anti-CTLA-4 and anti-PD-L1 immunotherapeutic approaches.

Serum protein changes in a rat model of chronic pain show a correlation between animal and humans.

In previous works we showed the overexpression of some proteins in biological fluids from patients suffering chronic pain. In this proteomic study we analysed serum from a rat model of neuropathic pain obtained by the chronic constriction injury (CCI) of sciatic nerve, at two time intervals, 2 and 5 weeks after the insult, to find proteins involved in the expression or mediation of pain. Sham-operated and CCI rats were treated with saline or indomethacin. Two weeks after ligation, we identified three serum proteins overexpressed in CCI rats, two of which, alpha-1-macroglobulin and vitamin D-binding protein (VDBP), remained increased 5 weeks post-surgery; at this time interval, we found increased levels of further proteins, namely apolipoprotein A-I (APOA1), apolipoprotein E (APOE), prostaglandin-H2 D-isomerase (PTGDS) and transthyretin (TTR), that overlap the overexpressed proteins found in humans. Indomethacin treatment reversed the effects of ligation. The qPCR analysis showed that transcript levels of APOA1, APOE, PTGDS and VDBP were overexpressed in the lumbar spinal cord (origin of sciatic nerve), but not in the striatum (an unrelated brain region), of CCI rats treated with saline 5 weeks after surgery, demonstrating that the lumbar spinal cord is a possible source of these proteins.

Desmoplastic melanoma: a challenge for the oncologist.

AIM: To evaluate clinical, pathologic and genetic features of desmoplastic melanoma (DM). MATERIALS & METHODS: Analysis of all DM records from 1991 to 2015. RESULTS: The most common location of DMs was the head and neck (69%); median age and follow-up were 60.5 and 7.3 years, respectively. A familial predisposition for DMs and others malignancies was analyzed. Thin Breslow thickness (<4.5 mm) was associated with an intraepidermal component or a previous lentigo maligna, whereas high Breslow thickness (>4.5 mm) was observed in 'pure' DM. CONCLUSION: DM could progress from an early phase, characterized by an intraepidermal component, to late phase, characterized by a dermal nodule. This hypothesis correlates with melanoma genetic and NF1 mutation, which could be an early event in the progression of DM.

Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer.

Thiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol-disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol-disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p < .001). There was a non-significant increase in the native thiol, total thiol and TAS levels in the patients six months after RP in comparison to the levels before RP (p values .3, .3 and .09, respectively). We found a significant negative correlation between PSA and thiol levels. Our study demonstrated that the decreased thiol and TAS levels weakened anti-oxidant defence mechanism in the patients with PC as indicated. Increased oxidative stress in prostate cancer patients may cause metabolic disturbance and have a role in the aetiopathogenesis of prostate cancer.