Enhancement of the Photosensitizing Properties of 6-Carboxypterin through Covalent Binding to the pH-Responsive and Biocompatible Poly(allylamine Hydrochloride).

A polymeric photosensitizer was synthesized through covalent attachment of the natural photosensitizer 6-carboxypterin (Cap) to a poly(allylamine hydrochloride) (PAH) polymer. The optimization of the functionalization steps and purification procedure is described. The overall yield of the functionalization reaction was 67% to generate the modified polymer (PAH-Cap), featuring a Cap substitution degree of approximately 1% and advantageous spectroscopic properties. Photosensitizing properties of PAH-Cap were observed to occur via both photooxidation mechanisms, i.e., type I and type II. This feature was demonstrated using a biologically relevant target molecule, 2'-deoxyguanosine (dG). The spectroscopic, photophysical, and photochemical behaviors in aqueous environments were studied and compared to Cap. To explore possible further relevant biological applications, experiments with PAH-Cap and dG were carried out at physiological pH. PAH-Cap can generate singlet molecular oxygen and initiate an electron transfer process at pH 7 in air-saturated solutions upon UVA irradiation. Moreover, based on its spectroscopic features, visible light can be used to initiate the photooxidation of biological compounds in water, with many interesting advantages compared to free Cap and other related pteridines. These advantages include an enhancement of the photosensitizing effect at physiological pH and the potential of PAH-Cap for its use as a building block in supramolecular assemblies. The functionalization strategy hereby described can be employed for the preparation of robust photoactive polymers with great potential for its application in photodynamic therapy (PDT) and disinfection technologies.

"Grafting-To" Covalent Binding of Plasmonic Nanoparticles onto Silica WGM Microresonators: Mechanically Robust Single-Molecule Sensors and Determination of Activation Energies from Single-Particle Events.

We hereby present a novel "grafting-to"-like approach for the covalent attachment of plasmonic nanoparticles (PNPs) onto whispering gallery mode (WGM) silica microresonators. Mechanically stable optoplasmonic microresonators were employed for sensing single-particle and single-molecule interactions in real time, allowing for the differentiation between binding and non-binding events. An approximated value of the activation energy for the silanization reaction occurring during the "grafting-to" approach was obtained using the Arrhenius equation; the results agree with available values from both bulk experiments and ab initio calculations. The "grafting-to" method combined with the functionalization of the plasmonic nanoparticle with appropriate receptors, such as single-stranded DNA, provides a robust platform for probing specific single-molecule interactions under biologically relevant conditions.

Patients' Perspectives on Race and the Use of Race-Based Algorithms in Clinical Decision-Making: a Qualitative Study.

BACKGROUND: Clinical algorithms that incorporate race as a modifying factor to guide clinical decision-making have recently been criticized for propagating racial bias in medicine. Equations used to calculate lung or kidney function are examples of clinical algorithms that have different diagnostic parameters depending on an individual's race. While these clinical measures have multiple implications for clinical care, patients' awareness of and their perspectives on the application of such algorithms are unknown. OBJECTIVE: To examine patients' perspectives on race and the use of race-based algorithms in clinical decision-making. DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: Twenty-three adult patients recruited at a safety-net hospital in Boston, MA. APPROACH: Interviews were analyzed using thematic content analysis and modified grounded theory. KEY RESULTS: Among the 23 study participants, 11 were women and 15 self-identified as Black or African American. Three categories of themes emerged: The first theme described definitions and the individual meanings participants ascribed to the term race. The second theme described perspectives on the role and consideration of race in clinical decision-making. Most study participants were unaware that race has been used as a modifying factor in clinical equations and rejected the incorporation of race in these equations. The third theme related to exposure to and experience of racism in healthcare settings. Experiences described by non-White participants ranged from microaggressions to overt acts of racism, including perceived racist encounters with healthcare providers. In addition, patients alluded to a deep mistrust in the healthcare system as a major barrier to equitable care. CONCLUSIONS: Our findings suggest that most patients are unaware of how race has been used to make risk assessments and guide clinical care. Further research on patients' perspectives is needed to inform the development of anti-racist policies and regulatory agendas as we move forward to combat systemic racism in medicine.

Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru; however, there are no prospective trials for adjuvant chemotherapy in GC after curative gastrectomy in this country. The objective of this study was to evaluate the effectiveness of adjuvant chemotherapy in stage II-III gastric cancer patients who underwent D2 gastrectomy. Methods: We included patients with stage II-III gastric cancer who underwent radical gastrectomy and D2 dissection between 2014 and 2016 at our institution. Patients received 3-week cycles of capecitabine (1,000 mg/m2 twice daily on days 1-14) plus oxaliplatin (130 mg/m2 on day 1) for 6 months. Survival curves were estimated with the Kaplan-Meier method, and the Cox proportional hazards model was used to identify prognostic factors for survival. Results: In total, 173 patients were included: 100 (57.8%) patients received adjuvant chemotherapy and surgery (AChS) and 73 (42.2%) surgery alone (SA). Three-year disease-free survival (DFS) was higher in the AChS groups (69%) than in the SA group (52.6%) (p = 0.034). Regarding overall survival (OS), 31 patients (31%) died in the AChS group compared with 34 (46.6%) in the SA group (p = 0.027). In the multivariate analysis, adjuvant chemotherapy was an independent prognostic factor for DFS (HR = 0.60; 95% CI = 0.37-0.97; p = 0.036) and OS (HR = 0.58; 95% CI = 0.36-0.95; p = 0.029). ACh showed consistent benefit in DFS and OS for patients with albumin >3.5 g/dL, lymphovascular and perineural invasion, pT4, pN2-3, pathologic stage (PS) IIIA and IIIB and lymph node ratio (LNR) > 13.1. Conclusion: These data suggest that adjuvant capecitabine and oxaliplatin reduce the recurrence and mortality in patients with stage II-III gastric cancer who underwent D2 gastrectomy. PS IIIA and IIIB and LNR > 13.1 benefited more from receiving adjuvant chemotherapy and poorly cohesive gastric carcinoma did not significantly reduce the rates of survival.

Guía de práctica clínica para el manejo del dolor en pacientes oncológicos de una red de clínicas privadas, Lima - Perú / Clinical practice guideline for pain management in cancer patients from a network of private clinics, Lima - Peru

Introducción: El presente artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de dolor en pacientes oncológicos. Este proceso se llevó a cabo con la participación de un equipo multidisciplinario de médicos asistenciales, metodólogos y diversos revisores externos (especialistas con dominio en la metodología y el tema). La priorización de preguntas PICO fue realizada por el Grupo Elaborador de la GPC (GEG), acordando trabajar cinco preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología GRADE y los lineamientos de la normativa nacional para la formulación de recomendaciones. Se formularon 12 recomendaciones (10 fuertes y 2 débiles), 5 puntos de buena práctica clínica y 4 cuadros consensuados sobre el manejo de dolor oncológico. Los temas que abarcaron las recomendaciones para el manejo de dolor en pacientes oncológicos fueron: intervención temprana de tratamiento, terapia analgésica en dolor leve a moderado y en dolor moderado a severo, dolor neuropático e intervenciones no farmacológicas.

Survival after curative pancreaticoduodenectomy for ampullary adenocarcinoma in a South American population: A retrospective cohort study.

BACKGROUND: Ampullary adenocarcinoma (AAC) is a rare neoplasm that accounts for only 0.2% of all gastrointestinal cancers. Its incidence rate is lower than 6 cases per million people. Different prognostic factors have been described for AAC and are associated with a wide range of survival rates. However, these studies have been exclusively conducted in patients originating from Asian, European, and North American countries. AIM: To evaluate the histopathologic predictors of overall survival (OS) in South American patients with AAC treated with curative pancreaticoduodenectomy (PD). METHODS: We analyzed retrospective data from 83 AAC patients who underwent curative (R0) PD at the National Cancer Institute of Peru between January 2010 and October 2020 to identify histopathologic predictors of OS. RESULTS: Sixty-nine percent of patients had developed intestinal-type AAC (69%), 23% had pancreatobiliary-type AAC, and 8% had other subtypes. Forty-one percent of patients were classified as Stage I, according to the AJCC 8th Edition. Recurrence occurred primarily in the liver (n = 8), peritoneum (n = 4), and lung (n = 4). Statistical analyses indicated that T3 tumour stage [hazard ratio (HR) of 6.4, 95% confidence interval (CI) of 2.5-16.3, P < 0.001], lymph node metastasis (HR: 4.5, 95%CI: 1.8-11.3, P = 0.001), and pancreatobiliary type (HR: 2.7, 95%CI: 1.2-6.2, P = 0.025) were independent predictors of OS. CONCLUSION: Extended tumour stage (T3), pancreatobiliary type, and positive lymph node metastasis represent independent predictors of a lower OS rate in South American AAC patients who underwent curative PD.

Guía de Práctica Clínica para el Manejo del Dolor en pacientes Oncológicos de una Red de Clínicas Privadas, Lima - Perú / Clinical Practice Guide for Pain Management in Oncological Patients from a Network of Private Clinics, Lima - Peru

Introducción: El presente artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de dolor en pacientes oncológicos. Este proceso se llevó a cabo con la participación de un equipo multidisciplinario de médicos asistenciales, metodólogos y diversos revisores externos (especialistas con dominio en la metodología y el tema). La priorización de preguntas PICO fue realizada por el Grupo Elaborador de la GPC (GEG), acordando trabajar cinco preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología GRADE y los lineamientos de la normativa nacional para la formulación de recomendaciones. Se formularon 12 recomendaciones (10 fuertes y 2 débiles), 5 puntos de buena práctica clínica y 4 cuadros consensuados sobre el manejo de dolor oncológico. Los temas que abarcaron las recomendaciones para el manejo de dolor en pacientes oncológicos fueron: intervención temprana de tratamiento, terapia analgésica en dolor leve a moderado y en dolor moderado a severo, dolor neuropático e intervenciones no farmacológicas.

Background: The article summarizes the process of elaboration of the Clinical Practice Guide (CPG) for the management of cancer patients. The elaboration process was carried out with the participation of a multidisciplinary team of assisting physicians, methodologists and various external reviewers (specialists with mastery in the methodology and the subject). The prioritization of PICO questions was carried out by the GPC Elaboration Group (GEG), after which 05 PICO questions were concluded. To answer the questions, a systematic search of CPGs, systematic reviews and primary studies was carried out. The "GRADE" methodology and the guidelines of national regulations were used to formulate recommendations. Twelve recommendations were made (ten strong and two weak),5 points of good clinical practice,04 consensus tables on the management of cancer pain. The topics that covered the recommendations for pain management in cancer patients were: early treatment intervention, analgesic therapy in mild to moderate pain and moderate to severe pain, neuropathic pain and non-pharmacological interventions

Clinician Advocacy and Intersex Health: A History of Intersex Health Care and the Role of the Clinician Advocate Past, Present, and Future.

Throughout the history of Western culture, sex has been reflected as a binary rule, with this binary system affecting self-expression, lifestyle choices, and health outcomes of everyone, but especially those with intersex traits. "Intersex" (or differences of sex development) is an umbrella term used to describe a wide range of natural variations in genitalia, gonads, and chromosome patterns that do not fit typical binary notions of male or female bodies. Currently, people who identify as intersex or as having intersex traits are not provided with the appropriate care needed for their wellbeing. Intersex health care has undergone a great deal of change in the last century, led by intersex leaders and advocates. Clinician advocates have also played a vital role. This article will focus on this history of intersex health care evolution, the role of clinician advocacy, and suggestions for how clinicians can become advocates for improving intersex health care. [Pediatr Ann. 2021;50(9):e359-e365.].

Review of biosensing with whispering-gallery mode lasers.

Lasers are the pillars of modern optics and sensing. Microlasers based on whispering-gallery modes (WGMs) are miniature in size and have excellent lasing characteristics suitable for biosensing. WGM lasers have been used for label-free detection of single virus particles, detection of molecular electrostatic changes at biointerfaces, and barcode-type live-cell tagging and tracking. The most recent advances in biosensing with WGM microlasers are described in this review. We cover the basic concepts of WGM resonators, the integration of gain media into various active WGM sensors and devices, and the cutting-edge advances in photonic devices for micro- and nanoprobing of biological samples that can be integrated with WGM lasers.

Oxidation of tyrosine: Antioxidant mechanism of l-DOPA disclosed.

Tyrosine is an amino acid related to crucial physiological events and its oxidation, that produce beneficial or detrimental effects on biological systems, has been extensively studied. Degradation of tyrosine often begins with the loss of an electron in an electron transfer reaction in the presence of a suitable electron acceptor. The reaction is facilitated by excited states of the acceptor in photosensitized processes. Several products of tyrosine oxidation have been described, the main ones being 3,4-dihydroxy-l-phenylalanine (commonly known as DOPA) and tyrosine dimers. Here, we report tyrosine recovery from tyrosyl radical, after one-electron oxidation, in the presence of DOPA. We propose that under high oxidative stress the oxidation of tyrosine may be controlled, in part, by one of its oxidation products. Also, we present strong evidence of antioxidant action of DOPA by preventing tyrosine dimerization, one of the most serious oxidative protein modifications, and the origin of structural modifications leading to the loss of protein functionality.

Evidence of the effectiveness of Resveratrol in the prevention of guanine one-electron oxidation: possible benefits in cancer prevention.

Over the past few years, the interest in Resveratrol (3,4',5,-trihydroxystilbene, RSV) has increased due to the evidence found of its antioxidant action that protects biomolecules and cells from oxidative damage. The interest has been further exacerbated by the natural presence of RSV in some fruits and derivatives, especially in red wine. In this paper we present evidence of RSV capacity in protecting a deoxynucleotide, an essential constituent of DNA, from one-electron oxidation. This article evaluates the mechanism responsible for the antioxidant action of RSV, after one-electron oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP), by kinetic analysis during steady-state irradiation and laser flash photolysis experiments. Results showed that RSV protects dGMP by recovering the nucleotide from its radical, which is formed after the reaction of dGMP with the triplet excited state of the photosensitizer. In the absence of RSV, dGMP is irremediably oxidized, and if the damage occurs in dGMP located in DNA molecules, the consequences can be as serious as mutations and subsequent carcinogenic lesions.

Fabrication and Characterization of Hollow Microcapsules from Polyelectrolytes Bearing Thymine Pendant Groups for Ultraviolet-B (UVB)-Induced Crosslinking.

DNA - bioinspired polyelectrolytes poly[vinylbenzylthymine (VBT)-4-vinylbenzyltriethylammonium chloride (VBA)] and poly[vinylbenzylthymine (VBT)-4-vinylphenylsufonate (VPS)] were used for the preparation of hollow microcapsules (HMC) using the layer-by-layer method and CaCO3 microspheres as removable molds. Stable aqueous suspensions of spherical-shaped HMCs with a shell composed of six layers of VBA-based polyelectrolytes were obtained, of approximately (7.0±1.5) µm diameter and a shell thickness of 1 µm. Ultraviolet-B irradiation of the HMC suspensions induces an efficient crosslinking between adjacent polyelectrolyte chains through the formation of thymine photodimers, such as the cyclobutane pyrimidine dimer (CPD) and the (6-4) pyrimidine-pyrimidone photoproduct (6-4PP). This process resulted in a reduction of the average interstitial mesh size of the HMC shells, modulating their permeability properties and increasing the mechanical stability of the HMC without a noticeable modification of size and shape. Thus, the DNA-bioinspired polyelectrolytes are promising materials for the preparation of UVB-responsive HMCs.

Photosensitizing properties of hollow microcapsules built by multilayer self-assembly of poly(allylamine hydrochloride) modified with rose Bengal.

A polymeric photosensitizer based on poly(allylamine hydrochloride) (PAH) and rose Bengal (RB) was synthesized. The modified polycation PAH-RB was demonstrated to be suitable for construction of microcapsules via a layer-by-layer (LbL) assembly technique, using sodium poly(styrene sulfonate) (PSS) as counter-polyelectrolyte and CaCO3 microcrystals as templates. After CaCO3 core removal, a stable suspension of hollow microcapsules with shells incorporating RB (HM-RB) was obtained. The spectroscopic and photophysical behavior of both PAH-RB and HM-RB in aqueous environments were studied and described in terms of dye-dye interactions and dye hydrophobicity. Only HM-RB was able to generate singlet molecular oxygen with similar efficiency to free RB in air-saturated solutions upon green light irradiation. In order to explore possible practical applications as a supramolecular photosensitizer, experiments of HM-RB irradiation in the presence of chemically and biologically relevant target molecules were carried out. It was observed that is possible to use visible light to initiate the photooxidation of biological compounds in water, with many interesting advantages compared to low-molecular-weight photosensitizers such as an enhancement of the photosensitizing effect, due to a significant reduction of dye-dye interaction, or improved reuse given the straightforward size-based separation from the reaction mixture without loss of efficiency.

Quenching of the Singlet and Triplet Excited States of Pterin by Amino Acids.

Unconjugated oxidized pterins accumulate in the skin of patients suffering from vitiligo and, under UVA irradiation, photosensitize the oxidation of amino acids. In this work, we study the interaction of the singlet and triplet excited states of pterin (Ptr), the parent compound of oxidized pterins, with four oxidizable amino acids: tryptophan (Trp), tyrosine (Tyr), histidine (His) and methionine (Met). Steady-state and time-resolved fluorescence measurements and laser flash photolysis experiments were performed to investigate the quenching of the Ptr excited states by the amino acids in aqueous solution. The singlet excited states of Ptr are quenched by Met mainly via a dynamic process and by Trp via a combination of dynamic and static processes. His does not quench singlet excited states of Ptr, and quenching by Tyr could not be investigated due to the low solubility of this amino acid. The triplet excited states of Ptr are quenched by the four studied amino acids, and the corresponding bimolecular quenching rate constants are in the range of diffusion controlled limit. The assessment of the results in the context of the Ptr-photosensitization of amino acids suggests that triplet excited state of Ptr is the species that initiates the photochemical processes.

Photophysical and Photochemical Properties of 3-methylpterin as a New and More Stable Pterin-type Photosensitizer.

Pterin derivatives are heterocyclic compounds which are present in different biological systems. Neutral aqueous solutions of pterins present acid-base and keto-enol equilibria. These compounds, under UV-A radiation fluoresce, undergo photooxidation, generate reactive oxygen species and photoinduce the oxidation of biological substrates. As photosensitizers, they may act through different mechanisms, mainly through an electron transfer-initiated process (type-I mechanism), but they also produce singlet molecular oxygen (1 O2 ) upon irradiation (type-II mechanism). In general, upon UV-A excitation two triplet states, corresponding to the lactim and lactam tautomers, are formed, but only the last one is the responsible for the photosensitized reactions of biomolecules. We present a study of the photochemical properties of 3-methylpterin (3-Mep) which, in contrast to most pterin derivatives, exists only in the lactam form. Also an improvement in the synthesis of 3-Mep is reported. The spectroscopic properties 3-Mep in aqueous solution were similar to those of the unsubstituted pterin derivative (Ptr) in its acid form, such as absorption, fluorescent and phosphorescent emission spectra. Experiments using 2'-deoxyguanosine 5'-monophosphate (dGMP) as oxidizable target demonstrated that methylation at C-3 position of the pterin moiety does not affect significantly the efficiency of photosensitization, but results in a more photostable sensitizer.

[Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas]. / Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas.

OBJECTIVE: To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. MATERIALS AND METHODS: Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. RESULTS: 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. CONCLUSIONS: Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

OBJETIVOS: Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. MATERIALES Y MÉTODOS: Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. RESULTADOS: 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. CONCLUSIONES: El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas / Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas

RESUMEN Objetivos Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. Materiales y métodos Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. Resultados 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. Conclusiones El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

ABSTRACT Objective To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Materials and methods Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. Results 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Conclusions Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

Predictors of survival of natural killer/T-cell lymphoma, nasal type, in a non-Asian population: a single cancer centre experience.

BACKGROUND: Natural killer/T-cell lymphoma (NKTCL), part of T-cell and NK-cell neoplasms in the World Health Organisation (WHO) classification, is an aggressive lymphoma with poor prognosis more predominantly seen in Asian and South American countries. This study evaluates the factors associated with survival among patients with newly diagnosed NKTCL in Peru. METHODS: Information was abstracted from medical records (MR) for all NKTCL patients >13 years of age at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2002 and 2011. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. RESULTS: Around 226 MR were reviewed, 153 met the selection criteria, the median age was 40 years (14-84). The median progression-free survival (PFS) was 20 months, five year PFS was 42.6%, univariable analysis (UA) showed statistical significance (p < 0.05) for male sex, non-nasal primary site, advanced clinical stages, B symptoms, poor performance status, regional nodal involvement (RNI). In the multivariate analysis the only poor prognostic factors was primary non-nasal (Hazard ratio (HR) = 2.40, 95% confidence interval (CI) = 1.43- 4.02, P = 0.01). The median overall survival (OS) was 49 months, five year OS was 48.9%, UA showed statistical significance for non-nasal primary site, advanced clinical stages, B symptoms, lactate dehydrogenase (LDH) > normal, RNI and local tumour invasion. In the multivariate analysis, primary non-nasal was the only poor prognostic factor with HR = 2.57, 95% CI = 1.37-4.83, P = 0.03. CONCLUSIONS: In Peru, OS of NKTCL is similar to other countries. This result suggests that non-nasal NKTCL is the only poor prognostic factor of OS and PFS.

Thymidine radical formation via one-electron transfer oxidation photoinduced by pterin: Mechanism and products characterization.

UV-A radiation (320-400nm), recognized as a class I carcinogen, induces damage to the DNA molecule and its components through different mechanisms. Pterin derivatives are involved in various biological functions, including enzymatic processes, and it has been demonstrated that oxidized pterins may act as photosensitizers. In particular, they accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. We have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to photosensitize the degradation of the pyrimidine nucleotide thymidine 5'-monophosphate (dTMP) in aqueous solutions under UV-A irradiation. Although thymine is less reactive than purine nucleobases, our results showed that Ptr is able to photoinduce the degradation of dTMP and that the process is initiated by an electron transfer from the nucleotide to the triplet excited state of Ptr. In the presence of molecular oxygen, the photochemical process leads to the oxidation of dTMP, whereas Ptr is not consumed. In the absence of oxygen, both compounds are consumed to yield a product in which the pterin moiety is covalently linked to the thymine. This compound retains some of the spectroscopic properties of Ptr, such as absorbance in the UV-A region and fluorescence properties.

Unraveling the Degradation Mechanism of Purine Nucleotides Photosensitized by Pterins: The Role of Charge-Transfer Steps.

Photosensitized reactions contribute to the development of skin cancer and are used in many applications. Photosensitizers can act through different mechanisms. It is currently accepted that if the photosensitizer generates singlet molecular oxygen ((1) O2 ) upon irradiation, the target molecule can undergo oxidation by this reactive oxygen species and the reaction needs dissolved O2 to proceed, therefore the reaction is classified as (1) O2 -mediated oxidation (type II mechanism). However, this assumption is not always correct, and as an example, a study on the degradation of 2'-deoxyguanosine 5'-monophosphate photosensitized by pterin is presented. A general mechanism is proposed to explain how the degradation of biological targets, such as nucleotides, photosensitized by pterins, naturally occurring (1) O2 photosensitizers, takes place through an electron-transfer-initiated process (type I mechanism), whereas the contribution of the (1) O2 -mediated oxidation is almost negligible.