Prognostic Value of Lactate Dehydrogenase in Patients with Melanoma Treated with Pembrolizumab.

INTRODUCTION: Elevated LDH levels have been extensively reported as a biomarker of poorer outcome in patients with melanoma during the chemotherapeutic era. The role of LDH level as a prognostic factor for treatment outcomes in patients with metastatic melanoma treated with immunooncological therapy has also been reported but requires further analysis. OBJECTIVES: In this study, we aimed to evaluate the prognostic value of lactate dehydrogenase (LDH) among patients with metastatic and unresectable melanoma treated with pembrolizumab in terms of progression-free survival (PFS). METHODS: The study included 59 patients with unresectable and metastatic melanoma treated with pembrolizumab. A comparison was performed between patients with normal and elevated levels of LDH in terms of PFS, with subgroup analysis. RESULTS: There was a significant reduction in PFS among patients with elevated levels of LDH compared with patients with normal levels of LDH (NR vs. 5 months; P=0.02). Patients with elevated LDH levels were older (P=0.01), with liver metastasis (P=0.004), and with less frequent CNS deposits (P=0.028). CONCLUSION: Although novel agents improved outcomes in patients with melanoma, high levels of LDH persist as an independent prognostic biomarker of poor prognosis.

Liposome-encapsulated peptide PDBSN ameliorates high-fat-diet-induced obesity and improves metabolism homeostasis.

In recent years, the obese and overweight population has increased rapidly, which has become a worldwide public health problem. However, effective medication is lacking. Our previous study identified a novel peptide, PDBSN (GLSVADLAESIMKNL), that could significantly restrict adipocyte differentiation in vitro, but its in vivo function has not been determined. Thus, in this study, we encapsulated the peptide into liposomes attached with two ligands (visceral-adipose-tissue-targeting peptide and cell-penetrating peptide) to improve stability and specificity. We then tested the peptide's function in HFD (high-fat diet)-induced obese mice and found that PDBSN could reduce weight gain and improve insulin resistance as well as lipid homeostasis. These results suggest that PDBSN may be a potential candidate for anti-obesity drug discovery.

The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.

There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non-neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.

Gastrointestinal stromal tumors during pregnancy: a systematic review of an uncommon but treatable malignancy

Although modern social structure and medical advances have led to the increasing number of women childbearing in older age, cancer remains a rare diagnosis during pregnancy. There is little given information throughout the literature concerning gestation associated with the coexistence of gastrointestinal stromal tumor (GIST). In this review, we present 12 reported cases of GIST during pregnancy and we discuss the maternal and fetal outcome, as well as the therapeutic plan that was followed in each situation. From the collected data, 8 out of 12 cases had an uneventful outcome of their fetus. In 11 out of 12 cases surgical excision of the tumor was the treatment of choice, while seven women were treated with imatinib. Two of them were already on imatinib therapy during conception due to preexisting GIST diagnosis. Surgery remains the gold standard for the treatment of local or resectable GIST, while published data concerning the use of imatinib during pregnancy indicate that teratogenicity or fetal loss might be induced, especially if given during the first trimester of pregnancy. GIST during gestational period is a rare tumor in which a multidisciplinary approach should be designed, taking always into consideration that it has a favorable outcome on targeted treatment (AU)

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High pretreatment neutrophil–lymphocyte ratio predicts recurrence and poor prognosis for combined small cell lung cancer

Backgrounds. Compared to pure small cell lung cancer (SCLC), combined small cell lung cancer (C-SCLC) has its own characteristics. High neutrophil to lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have been shown to be related to poor prognosis in several types of tumors. The aim of this study was to explore the prognosis value of NLR and PLR in patients with C-SCLC. Methods. A total of 112 patients diagnosed with C-SCLC between January 2000 and March 2009 were enrolled in the study. The clinicopathological parameters, laboratory analyses, and survival time were collected and analyzed. The correlation between NLR, PLR, and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. Results. The pretreatment NLR was elevated in 37.5 % patients (NLR ≥ 4.15; n = 42; H-NLR). NLR was significantly related to disease stage (p = 0.033) and tumor recurrence (p = 0.014). The median overall survival (OS) and progression-free survival (PFS) were significantly worse in the H-NLR group (OS: 22.0 months vs 11.7 months, p = 0.001; PFS: 11.1 vs 6.0 months, p < 0.001). However, PLR at diagnosis was not associated with OS or PFS. Multivariate analyses indicated elevated NLR (HR = 1.6; p = 0.001), disease stage (HR = 1.6; p = 0.001), and performance status (HR = 1.8; p = 0.015) as independent prognostic factors. Conclusions. High pretreatment NLR (≥4.15) is a potential useful indicator for C-SCLC recurrence and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients (AU)

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Influence of cryotherapy on muscle damage markers in jiu-jitsu fighters after competition: a cross-over study / Influencia de la crioterapia en la expresión de marcadores de daño muscular en luchadores de jiu-jitsu después de simulación de competición: estudio cruzado

Objetive. The acute effects of cryotherapy on creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) expression, perceived pain and upper limb muscle strength in jiu-jitsu competitors were investigated. Method. Ten highly trained athletes underwent two simulated competition sessions composed by four 7-minute combats with a 15-minute interval between them. Athletes were randomly allocated to receive either cold water immersion (5 ± 1 °C for 19 minutes) or no intervention (control) after competition simulation in a crossover counterbalanced fashion. Results. For LDH, there was an effect of condition (F1,18= 7.91, P = 0.012; η2 = 0.31), with lower values being found in cryotherapy as compared to control (criotherapy = 533.2 ± 55.4 and 671.2 ± 61.0 for pre- competition and post-recuperation, respectively; control = 528.5 ± 63.7 e 759.8 ± 85.7 UI/l for pre- competition and post-recuperation, respectively). Delta CPK differed significantly between conditions (criotherapy = 138.0 ± 95.1 UI/l; control = 231.3 ± 135.8 UI/l t = -1,72; P = 0,119; effect size = 0.75). For perceived pain there was also an effect of condition (F1,18 = 12.35, P = 0.003; η2 = 0.41), with lower values being found following cryotherapy (2.4 ± 1.4 versus 4.4 ± 1.8, P = 0.003). Pre-competition skin temperature was lower than that measured after recovery (34.5 ± 1.9 oC. versus 37.6 ± 1.3 oC, P = 0.0005). There were significant correlations between perceived pain and CPK (r = 0.314) and LDH (r = 0.546). The concentrations of CPK and LDH were negatively correlated with dynamic strength (r = - 0.525). Conclusion. Recovery via cold water immersion after simulated competition resulted in less muscle damage and hypoalgesia compared to the control (AU)

Objetivo. Investigar los efectos agudos de la crioterapia en la expresión de la enzima creatina fosfoquinasa (CPK), lactato deshidrogenasa (LDH), percepción del dolor y fuerza muscular en los miembros superiores de competidores de jiu-jitsu. Método. Diez luchadores altamente entrenados fueron sometidos a dos sesiones de competición simulada (4 × 7-minutos y 15 minutos de intervalo). Después del primer día, cinco atletas fueron elegidos para la inmersión en piscina con hielo (5 ± 1 °C) durante 19 minutos, los demás fueron asignados al grupo control. Resultados. Para LDH se observó efecto de la condición (F1,18 = 7,91, P = 0,012; η2 = 0,31) con valores más bajos (P = 0,012) en la crioterapia en comparación con el control (crioterapia = 533,2 ± 55,4 y 671,2 ± 61,0, respectivamente para inicial y final; control = 528,5 ± 63,7 y 759,8 ± 85,7 UI/l; respectivamente para inicial y final). El delta del CPK fue significativamente distinto entre las condiciones (crioterapia = 138,0 ± 95,1 UI/l; t = 1,72; P = 0,119; control = 231,3 ± 135,8 UI/l; tamaño del efecto = 0,75). Para el dolor percibido también hubo efecto de la condición (F1,18 = 12,35, P = 0,003; η2 = 0,41) con valores más bajos (P = 0,003) en la crioterapia (2,4 ± 1,4 frente a 4,4 ± 1,8). La temperatura corporal posrecuperación fue más baja en grupo crioterapia (P = 0,005) que la obtenida después en el control (34,5 ± 1,9°C frente a 37,6 ± 1,3°C). Se encontró correlación significativa entre la percepción del dolor y las concentraciones de CPK (r = 0,314) y LDH (r = 0,546). Las concentraciones de CPK y LDH se correlacionaron negativamente con la fuerza dinámica (r = 0,525). Conclusión. La recuperación usando la inmersión después de la competición resulta de un menor daño muscular e hipoalgesia (AU)