DNA cytosine and methylcytosine deamination by APOBEC3B: enhancing methylcytosine deamination by engineering APOBEC3B.

APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) is a family of enzymes that deaminates cytosine (C) to uracil (U) on nucleic acid. APOBEC3B (A3B) functions in innate immunity against intrinsic and invading retroelements and viruses. A3B can also induce genomic DNA mutations to cause cancer. A3B contains two cytosine deaminase domains (CD1, CD2), and there are conflicting reports about whether both domains are active. Here we demonstrate that only CD2 of A3B (A3BCD2) has C deamination activity. We also reveal that both A3B and A3BCD2 can deaminate methylcytosine (mC). Guided by structural and functional analysis, we successfully engineered A3BCD2 to gain over two orders of magnitude higher activity for mC deamination. Important determinants that contribute to the activity and selectivity for mC deamination have been identified, which reveals that multiple elements, rather than single ones, contribute to the mC deamination activity and selectivity in A3BCD2 and possibly other APOBECs.

Neoadjuvant Trastuzumab and Pertuzumab in Combination with Standard Chemotherapy for HER2-Positive Early Breast Cancer: Real-World Practice in Cuba.

PURPOSE: Dual HER2 blockade chemotherapy is the standard of care for localized HER2+ breast cancer (BC). However, despite the efficacy of neoadjuvant therapy, relapses occurring in around 10% of patients highlight the need to improve its clinical approach. Therefore, this study aimed to evaluate the effectiveness/safety of neoadjuvant therapy with subcutaneous (SC) trastuzumab- pertuzumab chemotherapy (real world) to extend the evidence, which comes mainly from clinical trials (selected population; intravenous [IV] trastuzumab). MATERIALS AND METHODS: A prospective, longitudinal, observational study in a Cuban hospital. POPULATION: women aged ≥18 years with histologically confirmed HER2+ early-stage BC (2017-2021) eligible for neoadjuvant treatment (IV pertuzumab, SC trastuzumab, taxane-based chemotherapy). The aim was to determine the pathological complete response (pCR) rate to this scheme, its safety, and the impact of patient's characteristics on the outcomes. RESULTS: Eighty-seven women were included: n=29 (DPT [docetaxel-IV pertuzumab- SC trastuzumab 600 mg; 4 cycles]); n=58 (ddAC-DPT [dose-dense anthracycline-based scheme+DPT]; 8 cycles). The median age was 57 years (range 30-83), ECOG 0: 97%. Time from diagnosis to treatment (median) was 28 days. The overall pCR rate was 62.1% (55.2%, DPT; 66.5%, ddAC-DPT; p =0.351); HR+, 47.7% vs. HR-, 76.7% (p=0.006). There were no statistically significant differences based on nodal status, stage, or Ki-67 levels. Overall, 94.2% of patients experienced ≥1 adverse event related to treatment, all of them grade 1-3 and more common with ddAC-DPT. The main cause of treatment delays (n=19; ddAC-DPT, 16; DPT, 3) was treatment-related toxicities. CONCLUSION: Neoadjuvant trastuzumab (SC) and pertuzumab plus chemotherapy for HER2+ early-stage BC showed benefits in a real-life setting, with an acceptable safety profile.

Nimotuzumab for Patients With Inoperable Cancer of the Head and Neck.

EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate affinity anti-EGFR antibody, that apart from other drugs in its class, is very safe and does not cause hypomagnesemia or grade 3-4 cutaneous rash. The antibody inhibits cell proliferation and angiogenesis, activates natural killer cells, stimulates dendritic cell maturation, and induces cytotoxic T cells. Nimotuzumab restores MHC-I expression on tumor cells, hindering one of the EGFR immune-escape ways. The antibody has been extensively studied in 7 clinical trials, concurrently with irradiation or irradiation plus chemotherapy in subjects with inoperable head and neck tumors. Nimotuzumab was safe and efficacious in unfit patients receiving irradiation alone and in subjects treated with cisplatin and radiotherapy. In patients with locally advanced squamous cell carcinomas of the head and neck, nimotuzumab in combination with low dose cisplatin and radiotherapy was superior to cisplatin and radiotherapy in progression free survival, disease free survival, and locoregional tumor control.

Implicancias de la biopsia selectiva de ganglio centinela en cadena mamaria interna en el cáncer de mama / Implications in selective sentinel node biopsy in internal mammary chain in breast cancer

RESUMEN El compromiso metastásico de los ganglios linfáticos es el factor pronóstico más importante en el cáncer de mama. Conocer el grado de infiltración de los mismos implica sobrevida libre de progresión, sobrevida global y riesgo de recurrencia temprana de la enfermedad, y esto a su vez ayudaría a conocer las terapias adyuvantes que recibirán las pacientes. Presentamos un caso con diagnóstico de carcinoma ductal invasor de la mama izquierda etapa IB que se le realizó biopsia selectiva de ganglio centinela mostrando la linfocentellografía, una migración única a la cadena mamaria interna sin poder acceder al mismo por su localización anatómica retrocostal, se decide rastreo y disección axilar porque así lo recoge nuestro protocolo, a partir de casos como este, nos obliga a realizar una revisión y actualización del tema, y así reajustar nuestros protocolos de actuación con la introducción de técnicas novedosas en nuestro país y los resultados de nuestras primeras experiencias acumuladas. La cadena mamaria interna puede ser el único territorio ganglionar comprometido en la biopsia selectiva de ganglio centinela y, a la vista de los resultados, podría obviarse el estudio ganglionar a nivel axilar cuando no hay sospecha clínica ni radiológica de afectación.

ABSTRACT Metastatic lymph node involvement is the most important prognostic factor in breast cancer. To know the degree of infiltration of the same involved progression-free survival, global survival and risk of early recurrence of the disease, and this in turn would help to know the adjuvant therapies that patients will receive. We present a case with a diagnosis of stage IB invasive ductal carcinoma of the left breast undergoing selective sentinel lymph node biopsy showing lymphocentellography, single migration to the internal mammary gland without access to it due to its retrocostal anatomical location, and axillary exploration and dissection were decided because this is what our protocol includes, based on cases like this, it forces us to carry out a review and update of the subject, and thus readjust our action protocols with the introduction of novel techniques in our country and the results of our first accumulated experiences. The internal mammary chain may be the only lymph node territory involved in selective sentinel lymph node biopsy and, in view of the results, it could obviate lymph node study at the axillary level when there is no clinical or radiological suspicion of involvement.

Reconstrucción mamaria posmastectomía con colgajo miocutáneo de dorsal ancho y expansión tisular / Posmastectomy breast reconstruction with latissimus dorsi myocutaneous flap and tissue expander

Introducción: El colgajo miocutáneo de dorsal ancho es una excelente opción para reconstruir la mama mutilada por enfermedad oncológica, pero tiene limitaciones en cuanto al volumen del implante a utilizar que garantice el cierre directo de la zona a tratar. De ahí que se consideró realizar este estudio utilizando el colgajo dorsal con un expansor mamario en el primer tiempo quirúrgico y luego la colocación del implante definitivo. Objetivo: caracterizar la experiencia de la reconstrucción mamaria con colgajo miocutáneo de músculo dorsal ancho y expansión tisular. Métodos: se realizó un estudio descriptivo longitudinal prospectivo de aquellas pacientes consultadas en el servicio de reconstructiva del Instituto Nacional de Oncología y Radiobiología (INOR) de La Habana, por presentar mastectomía por cáncer de mama. Se reconstruyeron a 20 pacientes, utilizando el colgajo miocutáneo de dorsal ancho con la utilización de expansor mamario. Luego de terminada la infiltración del expansor se esperaron 2 meses y se realizó el cambio del expansor por el implante definitivo y la remodelación de la mama contralateral. Resultados: el promedio de edad en el estudio fue de 43 años y el mayor porciento de casos se presentó entre las edades de 40 a 50 años. El tratamiento de la mama contralateral varió según las características de la misma y los deseos de la paciente. Se observaron complicaciones inmediatas como necrosis parcial del colgajo y complicaciones mediatas y tardías como extrusión y rotura del expansor. Se lograron resultados estéticos buenos y la mayoría de las pacientes manifestaron estar satisfechas con el proceder y con los resultados obtenidos. Conclusiones: todas las mujeres pudieron ser reconstruidas con adecuados resultados estéticos y algunas se favorecieron con mayor volumen de sus mamas(AU)

Introduction: the latissimus dorsi myocutaneous flap is an excellent option to reconstruct the breast mutilated for oncologic disease, but it has limitations regarding the volume of the implant to be used that guarantees the direct closure of the area to be treated. Hence, we considered to perform this study using the dorsal flap with a breast expander in the first time and then in a second time the placement of the definitive implant. Objective: to characterize the experience of breast reconstruction with myocutaneous flap of broad dorsal muscle and tissue expansion. Method: aprospective, longitudinal, descriptive study was carried out on patients consulted at the Reconstructive Service of National Institute for Oncology and Radiobiology (INOR) of Havana, for mastectomy due to breast cancer. 20 patients were reconstructed using the latissimus dorsi myocutaneous flap and a breast expander. After expiratory infiltration of the expander, we waited two months, and the expander change was made, using the definitive implant and remodeling of the contralateral breast. Results: the mean age in the study was 43 years and the highest percentage of cases were at ages 40-50 years. Treatment of the contralateral breast varied according to their characteristics and the patients' desires. Immediate complications were observed, such as partial necrosis of the flap and mediating and late complications such as extrusion and rupture of the expander. Good aesthetic results were achieved and most patients stated that they were satisfied with the procedure and the outcomes obtained. Conclusions: all women could be reconstructed with adequate esthetic outcomes and some were favored with greater volume of their breasts(AU)

Reconstrucción mamaria posmastectomía en el Instituto Nacional de Oncología y Radiobiología de Cuba (2008-2012) / Post-mastectomy breast reconstruction at the National Institute of Oncology and Radiobiology in Cuba (2008-2012)

Introducción: el impacto psicológico causado por la cirugía radical de la mama afecta la percepción de la propia imagen, y lo hace sumado al daño causado por la propia enfermedad. Este estudio tuvo como objetivo caracterizar experiencias en la reconstrucción mamaria posmastectomía. Métodos: se realizó un estudio prospectivo para caracterizar la experiencia en la reconstrucción mamaria posmastectomía en pacientes atendidas en el Instituto Nacional de Oncología y Radiobiología entre enero de 2008 y diciembre de 2012. Resultados: el grupo etario predominante estuvo integrado por mujeres entre 30 y 49 años. Predominaron los estadios I y II, y el carcinoma ductal infiltrante fue el más frecuente. Se realizó con mayor frecuencia la reconstrucción con expansión tisular, y le siguieron en frecuencia la reconstrucción con músculo dorsal ancho y la reconstrucción con músculo recto abdominal transverso (TRAM). El tipo de reconstrucción diferida fue la predominante, y en el tratamiento de la mama contralateral la técnica más empleada fue la mastoplastia reductora. Las principales complicaciones estuvieron relacionadas con la técnica empleada. Conclusiones: todas las mujeres pudieron someterse a la reconstrucción mamaria, y las técnicas quirúrgicas fueron aplicadas según las características específicas de cada paciente.

Introduction: the psychological impact of radical surgery of the breast affects the perception of the self-image in addition to the damage caused by the disease as such. This study was aimed at characterizing the experiences gained in post-mastectomy breast reconstruction. Methods: a prospective study was conducted to characterize the experiences gained in breast reconstruction after mastectomy in female patients seen at the National Institute of Oncology and Radiobiology from January 2008 through December 2012. Results: the predominant age group comprised women aged 30-49 years in I and II stagings, being the infiltrating ductal carcinoma the most frequent one. Reconstruction with tissue expansion was mostly performed, followed by reconstruction with wide dorsal muscle and reconstruction with transverse rectum abdominal muscle. The type of differed reconstruction was predominant. In the contralateral breast treatment, the most used technique was reductive mastoplasty. The main complications were associated to the type of surgical technique. Conclusions: all the operated women underwent breast reconstruction and the surgical techniques depended on the specific characteristics of each patient.

Reconstrucción de defectos torácicos complejos / Reconstruction of complex chest wall defects

Los grandes defectos torácicos requieren generalmente procedimientos complejos para su reparación; en la mayoría de los casos es necesaria la combinación de tejidos autólogos y materiales aloplásticos, por lo que constituye un desafío para el cirujano plástico. En nuestra institución los que se presentan suelen ser secundarios a exéresis tumoral, bien de origen primario o secundario. Se dispone de varias opciones reconstructivas para cubrir los amplios defectos resultantes de las amplias escisiones y poder aportar colgajos vascularizados, amplios y voluminosos. A pesar de no disponer en nuestro medio de técnicas avanzadas para el soporte rígido, hemos podido dar cobertura a todos los defectos y se ha garantizado una adecuada estabilidad de la pared torácica. Presentamos cuatro casos tratados por grandes defectos del tórax. Se tuvo como objetivo mostrar la forma en que se realizó la reconstrucción inmediata con la combinación de colgajos miocutáneos y material aloplástico(AU)

Reconstruction of large defects of the chest wall frequently requires the use of complex techniques that combines autologous tissues and alloplastic materials, which poses a real challenge for the cosmetic surgeon. Those chest defects that are seen in our institution are secondary to tumor excision, either of primary or of secondary origin. Many reconstructive options are necessary to cover large defects as a result of wide resection of tumors and to supply the defect with large, bulky and well vascularized flaps. Although advanced techniques for rigid support are not available in our conditions, it has been possible to cover all defects and to assure adequate stability of the chest wall. Four cases of large chest defects were presented in this paper. The objective was to show how the immediate reconstruction was carried out by combining autologous flaps and alloplastic materials(AU)