Prognostic significance of sentinel node biopsy status in cutaneous melanoma: a 21-years prospective study from a single institution.

AIM: To analyze the accuracy of the sentinel lymphatic node biopsy (SLNB) and to investigate predictive factors for sentinel node (SN) status and prognostic factors for recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with melanoma. MATERIAL AND METHODS: Between June 1997 and June 2017, 440 consecutive patients, who underwent SLNB by a single surgical team, were prospectively included. Descriptive and survival analysis were performed. RESULTS: 119 of 440 patients (26%) had positive SN. SLNB's false-negative rate was 6.3%. Breslow thickness, Clark´s level, ulceration and histological subtype were statistically significant predictive factors of SN metastases. In a multivariate analysis, positive SN (HR = 2.21, p = 0.01), deeper Breslow thickness (HR = 2.05, p = 0.013), male gender (RR = 2.05, p = 0.02), and higher Clark's level (HR = 2.30, p = 0.043) were significantly associated with decreased RFS; and positive SN (HR = 2.58, p < 0.001), deeper Breslow thickness (HR = 2.57, p = 0.006) and male gender (HR = 1.93, p = 0.006) were associated with lower DSS. CONCLUSION: SLNB is a reliable and reproducible procedure with high sensitivity (93.7%). Positive SN metastases, Breslow thickness and male gender were statistically associated with poorer outcomes. Male gender was an independent prognostic factor of tumor thickness or SN status.

Utility of PET/CT in patients with stage I-III melanoma.

PURPOSE: To study the utility of positron emission tomography with computerized tomography (PET/CT) in patients with a stage I-III melanoma. PATIENTS AND METHODS: PET/CT findings from all patients with a stage I-III melanoma attended at our hospital from September 2011 to November 2015 were reviewed. RESULTS: Data from 83 patients with a stage I-III melanoma, 39 patients with a positive sentinel lymph node biopsy (SLNB) and 35 patients with locoregional recurrences were analyzed. Sensitivity of PET/CT in clinical stage I-III patients was 5%, with a 14% of false positives. In patients with a positive SLNB, PET/CT previous to complete lymph node dissection had a 23% of false negatives. In patients with clinical locoregional recurrences, PET/CT findings revealed asymptomatic visceral distant metastasis in 25.7%. CONCLUSIONS: PET/CT has a significant rate of false positive and negative results in patients with a stage I-III melanoma. Utility in patients with nodal locoregional recurrences seems higher than in patients with skin metastases.

A new era in the treatment of melanoma: from biology to clinical practice.

Melanoma is the deadliest cutaneous malignancy and its incidence continues to grow. Until 2011, the treatment options for metastatic melanoma were scarce and without any overall survival benefit. The emergence of new targeted therapies for BRAF mutant melanoma (vemurafenib) and immunotherapy (ipilimumab) has changed the standard of care for this disease. The objective of the present review is to summarise the biological background of the new therapeutic approaches in melanoma, focusing on apoptosis resistance, immune modulation and angiogenesis, and the direct translation into clinical practice.

Analysis of regulatory elements of the promoter and the 3' untranslated region of the maize Hrgp gene coding for a cell wall protein.

Hydroxyproline-rich glycoproteins (HRGP) are structural components of the plant cell wall. Hrgp genes from maize and related species have a conserved 500 bp sequence in the 5'-flanking region, and all Hrgp genes from monocots have an intron located in the 3' untranslated region. To study the role of these conserved regions, several deletions of the Hrgp gene were fused to the beta-glucuronidase ( GUS) gene and used to transform maize tissues by particle bombardment. The overall pattern of GUS activity directed by sequential deletions of the Hrgp promoter was different in embryos and young shoots. In embryos, the activity of the full-length Hrgp promoter was in the same range as that of the p35SI promoter construct, based on the strong 35S promoter, whereas in the fast-growing young shoots it was 20 times higher. A putative silencer element specific for young shoots was found in the -1,076/-700 promoter region. Other major cis elements for Hrgp expression are probably located in the regions spanning -699/-510 and -297/-160. Sequences close to the initial ATG and mRNA leader were also important since deletion of the region -52/+16 caused a 75% reduction in promoter activity. The presence of the Hrgp intron in the 3' untranslated region changed the levels of GUS activity directed by the Hrgp and the 35S promoters. This pattern of activity was complex, and was dependent on the promoter and cell type analysed.

Presence of 5-hydroxy-indolacetic acid in Diloboderus abderus larvae without monoamine-oxidase-like activity.

The authors confirmed the presence of monoamines and 5-hydroxy-indolacetic acid (5-HIAA) in the cephalic region of Diloboderus abderus larvae employing a high pressure liquid chromatography (HPLC) with electrochemical detector. An anticholinesterase insecticide produced an increase in the serotonin and 5-HIAA endogenous levels, and did not modify the catecholamines. Monoamine-oxidase activity was undetectable with a radioactive method using 3H-tyramine as substrate.

Presence of 5-hydroxy-indolacetic acid in Diloboderus abderus larvae without monoamine-oxidase-like activity.

The authors confirmed the presence of monoamines and 5-hydroxy-indolacetic acid (5-HIAA) in the cephalic region of Diloboderus abderus larvae employing a high pressure liquid chromatography (HPLC) with electrochemical detector. An anticholinesterase insecticide produced an increase in the serotonin and 5-HIAA endogenous levels, and did not modify the catecholamines. Monoamine-oxidase activity was undetectable with a radioactive method using 3H-tyramine as substrate.

Antistress and antifatigue properties of Panax ginseng: comparison with piracetam.

The antistress and antifatigue properties of a Chinese ginseng preparation were tested on Swiss albino mice, exposed to various experimental models of stress, and were compared with those of piracetam. Both ginseng and piracetam were administered chronically in drinking water for 16-18 days as well as acutely, by injection, 30-60 min prior to the experiments. Reactivity of the mice, loss in body weight, amount of faeces, length of endurance and incidence of mortality were graded and measured. Both piracetam and ginseng treatment provided good protection against electroshock stress when compared to the untreated mice; fighting scores, incidence of tonic convulsion and mortality were significantly less in the treated groups. In the heat stress experiments, both piracetam and ginseng provided significant protection to the treated mice against exposure to heat. In the fatigue stress of forced swim test, ginseng treatment provided effective adaptation to fatigue and increased endurance in both male and female mice; piracetam showed some antifatigue effects on the male mice only. In the locomotor activity tests, ginseng did not depress motility, while piracetam did so in the later part of the tests. These results are discussed in the light of the antistress properties of the drugs as reported in the literature.

Antistress and antifatigue properties of Panax ginseng: comparison with piracetam.

The antistress and antifatigue properties of a Chinese ginseng preparation were tested on Swiss albino mice, exposed to various experimental models of stress, and were compared with those of piracetam. Both ginseng and piracetam were administered chronically in drinking water for 16-18 days as well as acutely, by injection, 30-60 min prior to the experiments. Reactivity of the mice, loss in body weight, amount of faeces, length of endurance and incidence of mortality were graded and measured. Both piracetam and ginseng treatment provided good protection against electroshock stress when compared to the untreated mice; fighting scores, incidence of tonic convulsion and mortality were significantly less in the treated groups. In the heat stress experiments, both piracetam and ginseng provided significant protection to the treated mice against exposure to heat. In the fatigue stress of forced swim test, ginseng treatment provided effective adaptation to fatigue and increased endurance in both male and female mice; piracetam showed some antifatigue effects on the male mice only. In the locomotor activity tests, ginseng did not depress motility, while piracetam did so in the later part of the tests. These results are discussed in the light of the antistress properties of the drugs as reported in the literature.

Effect on rats and mice of a diet with low tryptophan content (maize flour).

Female Wistar rats when crowded together become aggressive if fed a diet with low tryptophan (Trp) content (maize, flour, Mf). When isolated during 30 days and fed Mf they show a decrease of weight, of total plasma Trp, and of Trp and 5-hydroxytryptamine (5-HT) in brain stem, but 5-hydroxyindolacetic acid (5-HIAA) of the same cerebral area does not change. These results partially agree with other authors observations. Mice isolated during 47 days and fed with Mf do not show any significant weight variation, the hypermotility of isolated mice on normal diet persists, but 5-HT and 5-HIAA significantly decreases in total brain, an effect that has been observed by another author. The effect on 5-HIAA does not depend on the diet, either balanced or with low Trp content.

Effect on rats and mice of a diet with low tryptophan content (maize flour).

Female Wistar rats when crowded together become aggressive if fed a diet with low tryptophan (Trp) content (maize, flour, Mf). When isolated during 30 days and fed Mf they show a decrease of weight, of total plasma Trp, and of Trp and 5-hydroxytryptamine (5-HT) in brain stem, but 5-hydroxyindolacetic acid (5-HIAA) of the same cerebral area does not change. These results partially agree with other authors observations. Mice isolated during 47 days and fed with Mf do not show any significant weight variation, the hypermotility of isolated mice on normal diet persists, but 5-HT and 5-HIAA significantly decreases in total brain, an effect that has been observed by another author. The effect on 5-HIAA does not depend on the diet, either balanced or with low Trp content.

Effect on rats and mice of a diet with low tryptophan content (maize flour)

Female Wistar rats when crowded together become aggressive if fed a diet with low tryptophan (Trp) content (maize, flour, Mf). When isolated during 30 days and fed Mf they show a decrease of weight, of total plasma Trp, and of Trp and 5-hydroxytryptamine (5-HT) in brain stem, but 5-hydroxyindolacetic acid (5-HIAA) of the same cerebral area does not change. These results partially agree with other authors observations. Mice isolated during 47 days and fed with Mf do not show any significant weight variation, the hypermotility of isolated mice on normal diet persists, but 5-HT and 5-HIAA significantly decreases in total brain, an effect that has been observed by another author. The effect on 5-HIAA does not depend on the diet, either balanced or with low Trp content.