Association Study Among Candidate Genetic Polymorphisms and Chemotherapy-Related Severe Toxicity in Testicular Cancer Patients

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p < 0.2) and clinical conditions in relation to severe (III–IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III–IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p < 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III–IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p < 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy

Generalized Tree Volume Equations for Eucalyptus Genotypes under Contrasting Irrigation

Tree volume equations for Eucalyptus plantations are essential to estimate productivity, generalize equations that consider different genotypes and low-bias water regimes, and simplify plantation management. Our study evaluated the possibility of a generalized tree volume equation for eight Eucalyptus genotypes under contrasting irrigation regimens. We evaluated a seven-year-old plantation with eight Eucalyptus genotypes in two contrasting irrigation regimens (summer-irrigated vs. non-irrigated conditions). Diameter (DBH) and total height (H) measurements were considered in the tree equations (Schumacher and Hall (1933), Honer (1967), and Clutter et al. (1983)). The equation with the best fit considered the coefficient of determination, mean square error, and AIC and BIC parameters. The results showed that it is possible to use a generalized tree volume equation; the genotype, irrigation regime, and their interaction were not statistically significant for all equations. The best tree volume equation was Schumacher and Hall (1933), which showed the best fit and minor bias, with a small trend of underestimating the total volume in trees with a DBH >18.3 cm. These results suggest that it is possible to use a generalized tree volume equation to simplify plantation productivity projections while maintaining a good fit and low bias

Surgical treatment of gastric cancer: Results in 423 cases Resultados del tratamiento quirúrgico del cáncer gástrico. Análisis de 423 casos

Background: Gastric cancer is the second cause of cancer death worldwide and the first cause in Chile. Management of this pathology is controversial. Aim: To report the results on morbidity, mortality, and long-term survival rates of surgical treatment of gastric cancer, and compare them with those reported in the literature. Material and Methods: Follow up of 423 patients (aged 16 to 88 years, 271 males) operated for a gastric adenocarcinoma between 1996 and 2002. Patients were staged with the 5th edition of TNM staging system, and the 2nd edition in English of the Japanese Classification of Gastric Cancer. Morbidity was assessed using the classification of the Memorial Kettering Cancer Center group. Kapplan-Meier method was used to assay survival, and Log rank Test to compare long-term survivals. Results: Resectability of the lesions was 70.4%, and 88% of them corresponded to a curative-intended surgery. Seventy percent of patients were in stage TNM IIIA or higher at the moment of s

Increase of <i>Neisseria meningitidis</i> W:cc11 invasive disease in Chile has no correlation with carriage in adolescents

<div><p><i>Neisseria meningitidis</i> is a human exclusive pathogen that can lead to invasive meningococcal disease or may be carried in the upper respiratory tract without symptoms. The relationship between carriage and disease remains poorly understood but it is widely accepted that decreasing carriage by immunization should lead to a reduction of invasive cases. Latin America has experienced an increased incidence of serogroup W invasive cases of <i>Neisseria meningitidis</i> in the last decade. Specifically in Chile, despite low total incidence of invasive cases, serogroup W has become predominant since 2011 and has been associated with elevated mortality. Expecting to gain insight into the epidemiology of this disease, this study has used molecular typing schemes to compare <i>Neisseria meningitidis</i> isolates causing invasive disease with those isolates collected from adolescent carriers during the same period in Chile. A lower carriage of the serogroup W clonal complex ST-11/ET37 than expected was found; whereas, the same clonal complex accounted for 66% of total invasive meningococcal disease cases in the country that year. A high diversity of PorA variable regions and fHbp peptides was also ascertained in the carrier isolates compared to the invasive ones. According to the results shown here, the elevated number of serogroup W invasive cases in our country cannot be explained by a rise of carriage of pathogenic isolates. Overall, this study supports the idea that some strains, as W:cc11 found in Chile, possess an enhanced virulence to invade the host. Notwithstanding hypervirulence, this strain has not caused an epidemic in Chile. Finally, as genetic transfer occurs often, close surveillance of <i>Neisseria meningitidis</i> strains causing disease, and particularly hypervirulent W:cc11, should be kept as a priority in our country, in order to prepare the best response to face genetic changes that could lead to enhanced fitness of this pathogen.</p></div

Distribution of fHbp peptides within clonal complexes of NM isolates 2013.

<p>fHbp peptides were differentiated by colors within clonal complexes arranged as minimum spanning trees. a) fHbp peptides distribution within carrier isolates (N = 184) b) fHbp peptides distribution within invasive isolates (N = 119).</p

Distribution of fHbp peptides among NM isolates 2013.

<p>FHbp peptides for all isolates were arranged by modular groups as previously described [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193572#pone.0193572.ref032" target="_blank">32</a>]. Percentages from total are displayed on respective bars. a) fHbp peptides from carrier isolates (N = 184) or b) fHbp peptides from IMD isolates (N = 119). Modular group VI and I predominated among carrier isolates, whereas modular group III did among invasive isolates.</p

Distribution of PorA subtypes among NM isolates 2013.

<p>a) PorA profiles from carrier isolates presented as percentages b) PorA profiles from carrier isolates were differentiated by colors within clonal complexes resulting from minimum spanning tree analysis of MLST. c) PorA profiles percentages from IMD isolates. d) PorA profiles from invasive isolates indicated by colors within clonal complexes as in b). (*ND = non-determined). Compare the dominance of P1.5,2,36 subtype among invasive isolates and the diversity among carrier isolates.</p

Association study among candidate genetic polymorphisms and chemotherapy-related severe toxicity in testicular cancer patients

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p &lt; 0.2) and clinical conditions in relation to severe (III-IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III-IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p &lt; 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III-IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p &lt; 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy

Distribution of NM isolates 2013 by serogroups and clonal complexes.

<p>a) Isolates arranged by serogroup percentages show diversity among carriers whereas serogroups W and B account for almost all IMD isolates <b>(</b>N.G. = non-groupable). b) Isolates arranged by clonal complexes percentages resulting from MLST analysis presented a separation of serogroup B, both carriers and IMD isolates, into cc41/44 and cc32. Most NG isolates belonged to cc198, whereas all serogroup W isolates belonged to cc11. (Total number of samples: Carriers = 184 (9–19 yrs); IMD = 119 (any age)).</p