Does the ratio of eicosapentaenoic acid to docosahexaenoic acid matter in cancer treatment? A systematic review of their effects on cachexia-related inflammation.

Chronic inflammation is a hallmark of cancer cachexia. Polyunsaturated fatty acids (ω-3 PUFAs): eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to contribute to the reduction of inflammation, preservation of lean body mass and total body weight, and reduction of cancer-related symptoms, such as anorexia or neuropathy. This systematic review aimed to assess whether the ratio of EPA to DHA used in supplementation in cancer patients matters in the context of the resolution of inflammation and reduction of the risk of cachexia. The analysis included 20 randomized clinical trials with acceptable quality identified from the Pubmed/MEDLINE database. The significant results concerning the resolution of inflammation or improvement in nutritional status were the highest in the case of a low EPA/DHA ratio, i.e., 67%, and decreased, reaching 50% and 36% for the moderate and high ratios, respectively. Most results concerning body weight from high and moderate EPA/DHA ratios showed no benefit or were insignificant. A significant benefit in reducing any reported inflammatory markers was seen in the low EPA/DHA ratio subgroup at 63%, in the moderate at 29%, and in the high ratio subgroup at 11%. The greatest benefit in CRP reduction was obtained by patients during chemotherapy. The review questions the anticachectic and anti-inflammatory effect of ω-3 PUFAs supplementation with doses of EPA higher than DHA. A population that particularly benefits from ω-3 PUFAs supplementation are patients undergoing chemotherapy for advanced cancer.

The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies.

Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.

Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review.

Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term "morbidity" should be defined more clearly by the authors.

Cross-sectional observational study - Investigation of vitamin D concentration in Caucasian cancer patients. what is the adequate dose of vitamin D for these patients?

BACKGROUND & AIMS: Vitamin D impairs tumour-related transformation and supports the anticancer function of the immune system. Currently, there are no guidelines on vitamin D supplementation devoted solely to cancer patients. The primary objective of the study was to evaluate the frequency of vitamin D deficiency in Caucasian cancer patients and to characterize the clinical factors that predispose individuals to decreased vitamin D concentration. Secondly, the study aimed to estimate the dose of vitamin D supplementation that would prevent deficiencies in patients with cancer. METHODS: In the presented cross-sectional study the population consisted of 500 consecutive Caucasian patients with a diagnosis of neoplastic disease, some of which declared long-term vitamin D supplementation in various doses. Serum vitamin D concentration was measured once in all patients and clinical data were obtained from the hospital database. The frequencies of vitamin D deficiency were compared to certain clinical variables by appropriate statistical tests. The dose of vitamin D substitution in cancer patients was estimated using the receiver operating characteristic (ROC) curve. RESULTS: Vitamin D deficiency was diagnosed in 66.8% of patients with cancer and even in 31.6% who declared vitamin D supplementation. Older age, male gender, diagnosis of head and neck cancer or squamous cell carcinoma and body mass loss were identified as factors that predispose to vitamin D deficiency. The dose of vitamin D that would prevent deficiency in Caucasian patients with cancer was set at 2250 IU daily. CONCLUSIONS: Vitamin D deficiency was very common in Caucasian patients with cancer, even in terms of vitamin D supplementation. The greatest predisposition was related to elder age, male gender, diagnosis of head and neck or squamous cell carcinoma and body mass loss. The dose of vitamin D supplementation in cancer patients should probably be higher than in the general population.

Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer.

Gastric cancer (GC) is the fourth most common cause of cancer-associated death. Based on the age at diagnosis, GC is divided into early-onset GC (EOGC; ≤45 years) and conventional GC (CGC; >45 years). Mutations in the cell cycle checkpoint kinase 2 (CHEK2) and TP53 genes are associated with several types of cancer; however, their genetic defects in GC remain poorly understood. The aim of the present study was to determine the subcellular distribution of the CHEK2 protein and its redistribution following DNA damage, to improve the understanding of the DNA damage response. Genetic alterations and patterns of expression of CHEK2 and p53 proteins were investigated to identify potential biological markers and indicators of GC development. Additionally, the affected signaling pathways and their clinical importance in GC development and associated syndromes were investigated. A total of 196 GC samples (89 CGC and 107 EOGC samples) were used in the present study. DNA from 53 samples (18 CGC and 35 EOGC samples) was sequenced using targeted next-generation sequencing technology to identify and compare common and rare mutations associated with GC. Subsequently, the cytoplasmic and nuclear expression levels of CHEK2, phosphorylated (p)-CHEK2 at threonine 68 and p53 in GC tissues were determined via immunohistochemistry. Sequencing resulted in the identification of 63 single nucleotide polymorphisms (SNPs) in the CHEK2 gene amongst 5 different variants, and the intron variant c.319+379A>G was the most common SNP. In the TP53 gene, 57 different alterations were detected amongst 9 variant types, and the missense variant c.215C>G was the most common. Nuclear CHEK2 expression was high in both the EOGC and CGC subtypes. However, the prevalence of cytoplasmic CHEK2 expression (P<0.001) and nuclear p-CHEK2 expression (P=0.011) was significantly higher in CGC compared with in EOGC tissues. There was a statistically significant difference between high and low cytoplasmic CHEK2 expression in patients with p53-positive EOGC compared with in patients with p53-positive CGC (P=0.002). The present study was designed to determine the association between CHEK2 and p53 expression patterns in patients with EOGC and CGC, as well as genetic alterations in the CHEK2 and TP53 genes.

Expression of cyclooxygenase-2 and mucin 1 in colorectal cancer.

In colorectal cancer (CRC), pathological factors that correlate with negative prognosis include, among others, overexpression of cyclooxygenase-2 (COX-2) and abundant expression of mucin 1 (MUC1). COX-2 overexpression may therefore be associated with MUC1 overexpression. The aim of the present study was to investigate the possible correlation between COX-2 and MUC1 expression and to assess the correlation between their individual expression and the clinicopathological features of patients, paying particular attention to survival. The following data was collected from the 170 patients with CRC included in the present study: Age, sex, tumour localization, disease stage and survival. Tumour samples were immunostained with antibodies against COX-2 and MUC1. Protein expression was scored, relative to reference staining, and correlated with the clinicopathological data of patients. The results revealed no correlation between the expressions of COX-2 and MUC1, or with any of the studied clinicopathological variables. In addition, the expression of the two proteins were not associated. Neither of the proteins demonstrated prognostic value for survival. The present study did not confirm a direct relationship between the expressions of COX-2 and MUC1, or between the expression of either protein and the clinicopathological features of patients, including survival.