Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis.We express our deepest acknowledgement to patients and their families. The authors also acknowledge the computing resources and technical support provided by Abel Paz-Gallardo and Alfonso Pardo from Extremadura Research Centre for Advanced Technologies (CETA−CIEMAT). This work was supported FEDER cofounded MINECO grant SAF2015-66015-R, ISCIII-RETIC RD12/0036/0009, and PIE15/00076 and CB/16/00228 (to J.M. Paramio); MMF was supported by a Jose Castillejo Fellowship (CAS16/00115)

Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis

Viability and Burden of Leishmania in Extralesional Sites during Human Dermal Leishmaniasis

Understanding of the dynamics and distribution of Leishmania in the human host is fundamental to the targeting of control measures and their evaluation. Amplification of parasite gene sequences in clinical samples from cutaneous leishmaniasis patients has provided evidence of Leishmania in blood, other tissues and sites distinct from the lesion and of persistence of infection after clinical resolution of disease. However, there is uncertainty about the interpretation of the presence of Leishmania DNA as indicative of viable parasites. Because RNA is short-lived and labile, its presence provides an indicator of viability. We amplified Leishmania 7SLRNA, a molecule involved in intracellular protein translocation, to establish viability and estimate parasite load in blood monocytes, tonsil swab samples, and tissue fluid from healthy skin of patients with dermal leishmaniasis. Results showed that during active dermal leishmaniasis, viable Leishmania are present in blood monocytes, tonsils and normal skin in quantities similar to that in lesions, demonstrating widespread dissemination of infection and subclinical involvement of tissues beyond the lesion site. Leishmania 7SLRNA will be useful in deciphering the role of human infection in transmission

Age-standardized incidence and mortality rates of oral and pharyngeal cancer in Puerto Rico and among Non-Hispanics Whites, Non-Hispanic Blacks, and Hispanics in the USA

<p>Abstract</p> <p>Background</p> <p>In the American region, Puerto Rico (PR) has the highest incidence of oral and pharyngeal cancer (OPC), but racial/ethnic differences have never been assessed and compared with other groups in the United States of America (USA). We compared the age-adjusted incidence and mortality rates of OPC between PR and among USA Hispanics (USH), Non-Hispanic Whites (NHW), and Non-Hispanic Blacks (NHB) to assess the burden of this cancer in PR.</p> <p>Methods</p> <p>Analysis of the age-standardized rates (per 100,000) was performed using the direct method with the world standard population (ASR(World)) from 1998–2002. Annual percent change (APC) and Relative Risks (RR) were calculated using the Poisson regression model.</p> <p>Results</p> <p>The incidence ASR(World) for men in PR was constant (APC ≈ 0.0%), in contrast, a decrease was observed among NHW, NHB, and USH men, although only USH showed statistical significance (APC = -4.9%, p < 0.05). In women, the highest increase in incidence (APC = 5.3%) and the lowest decrease in mortality (APC = -1.4%) was observed in PR. The ratio of the ASR(World) showed that in all racial/ethnic groups, men had approximately 2–4 fold increased incidence and mortality risk of OPC than women (p < 0.05). Men in PR had a higher mortality risk (p < 0.05) of OPC as compared to USH, NHW, and NHB; but among women, PR showed a significant excess of mortality only as compared to USH (est. SRR = 1.82, 95% CI = 1.41, 2.33).</p> <p>Conclusion</p> <p>The overall higher incidence of OPC in men in PR as compared to USH, NHB, and NHW could be explained by the effect of gene-environment interactions. Meanwhile, the higher mortality from OPC in PR suggests limitations in the health-care access within this population. Further research is warranted to elucidate these findings.</p

Incidence and mortality rates of selected infection-related cancers in Puerto Rico and in the United States

<p>Abstract</p> <p>Background</p> <p>In 2002, 17.8% of the global cancer burden was attributable to infections. This study assessed the age-standardized incidence and mortality rates of stomach, liver, and cervical cancer in Puerto Rico (PR) for the period 1992-2003 and compared them to those of Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the United States (US).</p> <p>Methods</p> <p>Age-standardized rates [ASR(World)] were calculated based on cancer incidence and mortality data from the PR Cancer Central Registry and SEER, using the direct method and the world population as the standard. Annual percent changes (APC) were calculated using the Poisson regression model from 1992-2003.</p> <p>Results</p> <p>The incidence and mortality rates from stomach, liver and cervical cancer were lower in NHW than PR; with the exception of mortality from cervical cancer which was similar in both populations. Meanwhile, the incidence rates of stomach, liver and cervical cancers were similar between NHB and PR; except for NHB women who had a lower incidence rate of liver cancer than women in PR. NHB had a lower mortality from liver cancer than persons in PR, and similar mortality from stomach cancer.</p> <p>Conclusions</p> <p>The burden of liver, stomach, and cervical cancer in PR compares to that of USH and NHB and continues to be a public health priority. Public health efforts are necessary to further decrease the burden of cancers associated to infections in these groups, the largest minority population groups in the US. Future studies need to identify factors that may prevent infections with cancer-related agents in these populations. Strategies to increase the use of preventive strategies, such as vaccination and screening, among minority populations should also be developed.</p

A super-Earth and a sub-Neptune orbiting the bright, quiet M3 dwarf TOI-1266

We report the discovery and characterisation of a super-Earth and a sub-Neptune transiting the bright (K = 8.8), quiet, and nearby (37 pc) M3V dwarf TOI-1266. We validate the planetary nature of TOI-1266 b and c using four sectors of TESS photometry and data from the newly-commissioned 1-m SAINT-EX telescope located in San Pedro Mártir (México). We also include additional ground-based follow-up photometry as well as high-resolution spectroscopy and high-angular imaging observations. The inner, larger planet has a radius of R = 2.37_(−0.12)^(+0.16) R_⊕ and an orbital period of 10.9 days. The outer, smaller planet has a radius of R = 1.56_(−0.13)^(+0.15) R_⊕ on an 18.8-day orbit. The data are found to be consistent with circular, co-planar and stable orbits that are weakly influenced by the 2:1 mean motion resonance. Our TTV analysis of the combined dataset enables model-independent constraints on the masses and eccentricities of the planets. We find planetary masses of M_p = 13.5_(−9.0)^(+11.0) M_⊕ (<36.8 M_⊕ at 2-σ) for TOI-1266 b and 2.2_(−1.5)^(+2.0) M_⊕ (<5.7 M_⊕ at 2-σ) for TOI-1266 c. We find small but non-zero orbital eccentricities of 0.09_(−0.05)^(+0.06) (<0.21 at 2-σ) for TOI-1266 b and 0.04 ± 0.03 (< 0.10 at 2-σ) for TOI-1266 c. The equilibrium temperatures of both planets are of 413 ± 20 and 344 ± 16 K, respectively, assuming a null Bond albedo and uniform heat redistribution from the day-side to the night-side hemisphere. The host brightness and negligible activity combined with the planetary system architecture and favourable planet-to-star radii ratios makes TOI-1266 an exquisite system for a detailed characterisation

A super-Earth and a sub-Neptune orbiting the bright, quiet M3 dwarf TOI-1266

We report the discovery and characterisation of a super-Earth and a sub-Neptune transiting the bright ($K=8.8$), quiet, and nearby (37 pc) M3V dwarf TOI-1266. We validate the planetary nature of TOI-1266 b and c using four sectors of TESS photometry and data from the newly-commissioned 1-m SAINT-EX telescope located in San Pedro M\'artir (Mexico). We also include additional ground-based follow-up photometry as well as high-resolution spectroscopy and high-angular imaging observations. The inner, larger planet has a radius of $R=2.37_{-0.12}^{+0.16}$ R$_{\oplus}$ and an orbital period of 10.9 days. The outer, smaller planet has a radius of $R=1.56_{-0.13}^{+0.15}$ R$_{\oplus}$ on an 18.8-day orbit. The data are found to be consistent with circular, co-planar and stable orbits that are weakly influenced by the 2:1 mean motion resonance. Our TTV analysis of the combined dataset enables model-independent constraints on the masses and eccentricities of the planets. We find planetary masses of $M_\mathrm{p}$ = $13.5_{-9.0}^{+11.0}$ $\mathrm{M_{\oplus}}$ ($<36.8$ $\mathrm{M_{\oplus}}$ at 2-$\sigma$) for TOI-1266 b and $2.2_{-1.5}^{+2.0}$ $\mathrm{M_{\oplus}}$ ($<5.7$ $\mathrm{M_{\oplus}}$ at 2-$\sigma$) for TOI-1266 c. We find small but non-zero orbital eccentricities of $0.09_{-0.05}^{+0.06}$ ($<0.21$ at 2-$\sigma$) for TOI-1266 b and $0.04\pm0.03$ ($<0.10$ at 2-$\sigma$) for TOI-1266 c. The equilibrium temperatures of both planets are of $413\pm20$ K and $344\pm16$ K, respectively, assuming a null Bond albedo and uniform heat redistribution from the day-side to the night-side hemisphere. The host brightness and negligible activity combined with the planetary system architecture and favourable planet-to-star radii ratios makes TOI-1266 an exquisite system for a detailed characterisation