Effects of rosmarinic acid and doxorubicine on an ovarian adenocarsinoma cell line (OVCAR3) via the EGFR pathway

Purpose: We aimed to reveal the effects of rosmarinic acid (RA), which has come to the forefront with its antitumor and antioxidant properties in many studies recently in the ovarian adenocarcinoma cell line, on the epidermal growth factor receptor (EFGR) signaling pathway in the presence of doxorubicin (DOX). Methods: Ovarian adenocarcinoma cell line (OVCAR3) and human skin keratinocyte cell line human skin keratinocyte cell line (HaCaT) were used as control. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied to determine the effect of RA and DOX on the proliferation of OVCAR3 and HaCaT cells. Bcl2 expression and epidermal growth factor receptor (EGFR) and western blot analysis were performed to determine the expression levels of the markers. Results: It was determined that RA (IC50 = 437.6 µM) and DOX (IC50 = 0.08 µM) have the ability to inhibit the proliferation of OVCAR3 cells and induce apoptosis in a 72-hour time and dose-dependent manner. Western blot showed that the expression level of Bcl-2 and EGFR in OVCAR3 cells was down-regulated by RA and DOX. Conclusions: Apoptosis in OVCAR3 cells can potentially be induced by RA via the EGFR pathway, and RA may be a potent agent for cancer therapy.

Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment / 口腔疾病防治

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Cisto gigante de segundo arco branquial em adulto: Relato de caso e revisão de literatura / Giant cyst of the second branchial arch in an adult: case report and literature review

Introdução: Os arcos branquiais são os precursores embriológicos da face, pescoço e faringe. As anomalias dos arcos branquiais são a segunda lesão congênita mais comum de cabeça e pescoço em crianças. Entre essas anomalias, estão os cistos de arcos branquiais (BCC), que surgem devido a uma incorreta obliteração das fendas branquiais, ainda no período embrionário. Os BCC podem ser assintomáticos, apenas percebidos incidentalmente, e não se manifestar até a idade adulta. Resultados: Anomalias do segundo arco branquial devem ser consideradas como um dos possíveis diagnósticos diferenciais de massas cervicais, especialmente as que se manifestam como um abaulamento em região lateral do pescoço. Os BCC são formações de revestimento epitelial, sem aberturas externas. Após seu diagnóstico, o tratamento é cirúrgico, usualmente por meio de uma incisão cervical transversa e cuidadosa dissecação das estruturas, com o objetivo de extirpar toda a lesão. Conclusão: O método descrito, de excisão da lesão, por meio de incisão transversa em região cervical, dissecção tecidual por planos e ressecção de massa cística, é uma opção para o tratamento dessa deformidade, com adequado resultado estético e boa reprodutibilidade.

Introduction: The branchial arches are the embryological precursors of the face, neck, and pharynx. Branchial arch anomalies are the second most common congenital head and neck lesions in children. Among these anomalies are branchial arch cysts (BCC), which arise due to incorrect obliteration of the branchial slits, still in the embryonic period. BCCs may be asymptomatic, only noticed incidentally, and not manifest until adulthood. Results: Anomalies of the second branchial arch should be considered as one of the possible differential diagnoses of neck masses, especially those that manifest as a bulge in the lateral region of the neck. BCCs are epithelial lining formations without external openings. After diagnosis, treatment is surgical, usually through a transverse cervical incision and careful dissection of the structures, with the aim of extirpating the entire lesion. Conclusion: The method described of excision of the lesion through a transverse incision in the cervical region, tissue dissection in planes, and resection of the cystic mass is an option for the treatment of this deformity, with adequate aesthetic results and good reproducibility.

Síndrome Stevens Jonhson: reporte de caso clínico / Stevens Johnson syndrome: clinical case report

Resumen Introducción: El síndrome Stevens Johnson (SSJ) es una dermatosis potencialmente fatal caracterizada por una extensa necrosis epidérmica y de mucosas que se acompaña de ataque al estado general, y junto con la necrólisis epidérmica tóxica (NET) se consideran reacciones de hipersensibilidad tipo IV, relacionadas con ciertos fármacos en 60% de los casos, siendo uno de los diagnósticos pocos frecuentes, pero con una alta mortalidad hasta del 40%. Caso clínico: El siguiente caso clínico es un masculino de 34 años de edad que inició un cuadro de eritema generalizado inmediatamente tras la administración del medicamento trimetoprima/sulfametoxazol. Se le solicitó un hemograma mostrando leucocitosis, neutrofilia, VSG elevada, PCR elevada, IgE elevada, y tras el interrogatorio clínico se realiza el algoritmo ALDEN dando positivo con 10 puntos asociado al medicamento previamente dicho. Por lo tanto se le inicia tratamiento con metilprednisolona, difenhidramina, inmunoglobulina humana intravenosa y un plan terapéutico cutáneo, dando como resultado una mejoría clínica, evitando complicaciones y secuelas, hasta el día de su egreso. A manera de conclusión, se requiere un manejo multidisciplinario para atender las manifestaciones clínicas del inmunoglobulina humana intravenosa.

Abstract Introduction: Stevens Johnson Syndrome (SJS) is a potentially fatal dermatosis characterized by extensive epidermal and mucosal necrosis accompanied by an attack on the general condition, which together with Toxic Epidermal Necrolysis (TEN) are considered type IV hypersensitivity reactions, related to certain drugs in 60% of cases, being one of the rare diagnoses, but with a high mortality of up to 40%. Case report: The following clinical case is a 34 year old male who started a generalized erythema picture immediately after administration of the medication trimethoprim/sulfamethoxazole, for which a complete blood count was requested showing leukocytosis, neutrophilia, elevated ESR, elevated PCR, elevated IgE, and after the clinical questioning, the ALDEN algorithm was performed, giving positive with 10 points associated with the previously mentioned medication, for which treatment was started with methylprednisolone, diphenhydramine, intravenous human immunoglobulin and a skin therapeutic plan, resulting in clinical improvement, avoiding complications and sequelae, until the day of discharge. In conclusion, a multidisciplinary management is required to attend to the clinical manifestations of the patient, helping him to a quick and effective recovery.

Comparative study of the efficacy and safety of two grafting procedures (an automated epidermal harvesting system and non-cultured epidermal cell suspension) in the treatment of stable vitiligo

Background: The non-cultured epidermal cell suspension method is a well-established but tedious grafting modality in the management of stable vitiligo. Recently a more user-friendly automated epidermal harvesting system has been introduced. Aim: This was a pilot study to compare the efficacy and safety outcomes of the above two grafting procedures. Study design: The study was a single-blinded split-body randomised controlled trial. After scientific and ethical clearance, the trial was registered with CTRI (CTRI/2018/05/014225). Thirty consenting patients of stable vitiligo with 60 near-symmetrical patches were recruited. Block randomisation was done using computer-generated randomisation software and each patch was allocated either of the two grafting modalities. Efficacy was assessed by the Physician Global Assessment Scale on serial images and pain by the Numerical Rating Pain Scale. Results and conclusion: The non-cultured epidermal cell suspension was found to be an overall statistically superior technique to the automated epidermal harvesting system in terms of efficacy (re-pigmentation). Both donor and recipient site complications were significantly less with the automated epidermal harvesting system grafting and this method had the distinct advantage of being a painless and easy technique with minimal recovery time. A novel observation was that a good colour match and near-complete re-pigmentation occurred in patients with a darker skin colour with both techniques. Limitations: The main limitation of our study was the small sample size. Also, the size of the treated patches was limited such that they could be covered by the 5 × 5 cm size of the automated epidermal harvesting system blade. However, a larger area can be covered with multiple sessions.

Síndrome de Stevens-Johnson y Necrólisis epidérmica tóxica: presentación en un paciente pediátrico / Stevens-Johnson syndrome and toxic epidermal necrolysis: presentation in a pediatric patient

El síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET), constituyen el espectro de una enfermedad aguda, originada por una reacción de hipersensibilidad, secundaria a ingesta de medicamentos o infecciones, que afecta la piel y las membranas mucosas, causadas por apoptosis y posterior necrosis de los queratinocitos. Se presenta un escolar masculino de 8 años de edad, con antecedente de epilepsia estructural, a quien en su último control por Neuropediatría, se le indicó tratamiento con Lamotrigina, presentando posteriormente lesiones tipo pápulas faciales, que progresaron rápidamente en sentido céfalo caudal; a las 48 horas, las lesiones evolucionaron a pústulas en mentón, y posteriormente a flictenas. Se utilizaron medidas de soporte vital, limpieza quirúrgica, obteniéndose mejoría clínica progresiva, incluyendo recuperación de las lesiones en piel. El aislamiento temprano por contacto, los cuidados de la piel y la mínima invasión, fueron factores fundamentales en la evolución satisfactoria de este paciente(AU)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) constitute the spectrum of an acute disease, caused by a hypersensitivity reaction, secondary to medication intake or infections, which affects the skin and mucous membranes. Caused by apoptosis and subsequent necrosis of keratinocytes. An 8-year-old male schoolboy is presented, with a history of structural epilepsy, who was prescribed treatment with Lamotrigine during his last Neuropediatric check-up, subsequently presenting facial papule-type lesions, which progressed rapidly in the cephalocaudal direction; 48 hours later, the lesions evolved into pustules on the chin, and later to blisters. Life support measures and surgical cleaning wereused, obtaining progressive clinical improvement, including recovery of skin lesions. Early contact isolation, skin care and minimal invasion were fundamental factors in the satisfactory evolution of this patient(AU)

Ozonoterapia como apoyo en el tratamiento de la úlcera del pie diabético. Presentación de un caso

Una de las complicaciones más comunes de la diabetes mellitus es la úlcera del pie diabético, como una fuente importante de morbilidad y mortalidad. Se presenta el caso de una paciente de 43 años, con diagnóstico de diabetes mellitus tipo 2, de siete años de evolución, remitida desde el Cuerpo de Guardia del Policlínico Universitario Dr. Mario Muñoz Monroy, de Abreus, con el diagnóstico de pie diabético neuroinfeccioso complicado con un absceso. Se realizó drenaje del absceso, modificación del tratamiento con insulina y desbridamiento de la lesión. Además, se indicó antibiótico y Heberprot-P®. Ante la ausencia de evolución satisfactoria, se realizó nuevo desbridamiento, con amputación de tercer y cuarto dedos del pie izquierdo; se retomó el tratamiento inicial, eta vez combinado con ozonoterapia vía local y rectal. A partir de la semana 18 la paciente evolucionó favorablemente, con presencia de buena granulación, desaparición gradual del dolor y aceleración del proceso de cicatrización completa de la lesión, además de conseguir un control metabólico eficiente. El caso descrito confirma la eficacia y seguridad del uso combinado del Heberprot-P® y la terapia con ozono.

One of the most common complications of diabetes mellitus is diabetic foot ulcer, as an important source of morbidity and mortality. The case of a 43-years-old patient with a diagnosis of type 2 diabetes mellitus, of seven years of evolution, referred from the Emergency Department of the Dr. Mario Muñoz Monroy University Polyclinic, Abreus, with the diagnosis of neuroinfectious diabetic foot complicated with an abscess is presented. Drainage of the abscess, modification of insulin treatment, and debridement of the lesion were performed. In addition, antibiotics and Heberprot-P® were indicated. In the absence of satisfactory evolution, new debridement was performed, with amputation of the third and fourth toes of the left foot; the initial treatment was resumed, this time combined with local and rectal ozone therapy. From week 18 on, the patient progressed favorably, with the presence of good granulation, gradual disappearance of pain and acceleration of the complete healing process of the lesion, in addition to achieving efficient metabolic control. The described case confirms the efficacy and safety of the Heberprot-P® combined use and ozone therapy.

TEN mimics: Classification and practical approach to toxic epidermal necrolysis-like dermatoses

Toxic epidermal necrolysis (TEN) is an acute life-threatening dermatologic emergency. However, many dermatoses can present with a TEN-like eruption. Those “TEN-mimics” are a true diagnostic challenge and an alarming differential diagnosis to such a serious condition. Herein, we will expose and classify the landscape of TEN-mimics. Also, the key differentiating clinical and/or laboratory points will be highlighted to help an accurate diagnosis of either a TEN or a TEN-like presentation.

Presentación simultánea de quiste epidermoide del ángulo pontocerebeloso y colesteatoma infiltrante del oído medio. Reporte de caso y revisión de literatura / Simultaneous presentation of an epidermoid cyst of the cerebellopontine angle and infiltrating cholesteatoma of the middle ear. Case report and literature review

Introducción: los quistes epidermoides son el tercer tumor más común del ángulo pontocerebeloso (APC). Es infrecuente detectar simultáneamente un colesteatoma infiltrativo del oído medio (OM). Caso clínico: paciente de 51 años acude a urgencias por cefalea hemicraneal intensa, pulsátil secundaria a hidrocefalia aguda, requirió ventriculostomía. En la resonancia magnética nuclear (RMN) cerebral contrastada se reporta una masa en el APC sugestivo de quiste epidermoide y simultáneamente un colesteatoma infiltrativo del OM. La paciente fue intervenida primero con resección de colesteatoma del OM; en un segundo tiempo resección del quiste epidermoide del APC por vía translaberíntica. El posoperatorio la evolución clínica fue satisfactoria. Discusión: los quistes epidermoides del APC son histopatológicamente idénticos al colesteatoma del OM y pueden ser secundarios a estos. Conclusión: se debe individualizar el manejo sin descartar la posibilidad de tener las dos enfermedades de manera simultánea.

Introduction: cysts are the third most common tumor of the cerebellopontine angle (CPA). It is rare to simultaneously detect an infiltrative cholesteatoma of the middle ear (OM). Clinical case: a 51-year-old patient attended the emergency department due to intense throbbing hemicranial headache secondary to acute hydrocephalus, requiring ventriculostomy. Contrast-enhanced cerebral magnetic resonance imaging (MRI) reported a mass in the APC suggestive of an epidermoid cyst and simultaneously an infiltrative cholesteatoma of the OM. The patient underwent first surgery with resection of the OM cholesteatoma; in a second stage, resection of the epidermoid cyst of the APC through a translabyrinthine approach. The postoperative clinical evolution was satisfactory. Discussion: APC epidermoid cysts are histopathologically identical to OM cholesteatoma and may be secondary to them. Conclusion: management must be individualized without ruling out the possibility of having both diseases simultaneously.

Heberprot-P® en el tratamiento de trauma vascular distal / Heberprot-P® in the treatment of distal vascular trauma

Introducción: Los traumatismos constituyen causa frecuente de consulta. Entre sus localizaciones más comunes se encuentran las extremidades inferiores. El Heberprot-P® resulta un factor de crecimiento epidérmico que se ha utilizado durante más de una década para la cicatrización de las úlceras del pie diabético con excelentes resultados. Ampliar su utilización a otras patologías, incluso de etiología traumática, permitiría expandir las posibilidades terapéuticas para la cicatrización de las heridas. Objetivo: Exponer el resultado de la aplicación del Heberprot-P® en una amputación transtarsiana en un paciente portador de un trauma vascular distal. Presentación del caso: Paciente masculino de 23 años con antecedentes de salud. Luego de traumatismo por accidente de tránsito presentó fractura de huesos del metatarso y la sección total de la arteria pedia del pie izquierdo, lo cual provocó una gangrena húmeda de la extremidad. Por este motivo se realizó una amputación transtarsiana del pie. Se usó el Heberprot-P® como terapia para acortar el tiempo de cicatrización. Conclusiones: El Heberprot-P® resultó útil para la evolución de la herida como consecuencia de un trauma vascular, al evitar una amputación mayor, acelerar el proceso de cicatrización y conservar una extremidad funcional, lo que demostró que puede constituir una terapia eficaz para las heridas de difícil cicatrización, independientemente de su etiología(AU)

Introduction: Trauma is a frequent cause of consultation. Among its most common locations are the lower extremities. Heberprot-P® is an epidermal growth factor that has been used for more than a decade for the healing of diabetic foot ulcers with excellent results. Extending its use to other pathologies, including traumatic etiology ones, would expand the therapeutic possibilities for wound healing. Objective: To present the result of the application of Heberprot-P® in a Chopart´s amputation in a patient with distal vascular trauma. Case presentation: A 23-year-old male patient with a health history. After trauma from a traffic accident, he presented a fracture of the bones of the metatarsus and the whole section of the left foot´s pedis artery, which caused a wet gangrene of the extremity. For this reason, a Chopart´s amputation of the foot was performed. Heberprot-P® was used as therapy to shorten healing time. Conclusions: Heberprot-P® was useful for wound evolution as a result of vascular trauma, avoiding major amputation, accelerating the healing process and preserving a functional limb, which showed that it can be an effective therapy for wounds that are difficult to heal, regardless of their etiology(AU)

Investigation the Effect of Human Recombinant Epidermal Growth Factor on Rotator Cuff Healing: An Experimental Model / Investigação do efeito do fator de crescimento epidérmico recombinante humano na cicatrização do manguito rotador: Um modelo experimental

Abstract Objective To investigate the effectiveness of human recombinant epidermal growth factor in the healing of rotator cuff tear in the rabbit shoulder. Methods Rotator cuff tears (RCTs) were experimentally created on both shoulders of 20 New Zealand rabbits. The rabbits were divided into the following groups: RCT (sham group; n = 5), RCT + EGF (EGF group; n = 5), RCT + transosseous repair (repair group; n = 5), and RCT + EGF + transosseous repair (combined repair + EGF group; n = 5). All rabbits were then observed for 3 weeks, and biopsies were taken from the right shoulders in the third week. After three more weeks of observation, all rabbits were sacrificed, and a biopsy removed from their left shoulders. All biopsy material was stained with haematoxylin & eosin (H&E) and vascularity, cellularity, the proportion of fibers and the number of fibrocartilage cells were evaluated under light microscope. Results The highest collagen amount and the most regular collagen sequence was detected in the combined repair + EGF group. The repair group and the EGF group showed higher fibroblastic activity and capillary formation when compared with the sham group, but the highest fibroblastic activity and capillary formation with highest vascularity was detected in the combined repair + EGF group (p < 0.001). EGF seems to improve wound healing in the repair of RCT. The EGF application alone, even without repair surgery, seems to be beneficial to RCT healing. Conclusion In addition to rotator cuff tear repair, application of human recombinant epidermal growth factor has an effect on rotator cuff healing in rabbit shoulders.

Resumo Objetivo Investigar a eficácia do fator de crescimento epidérmico (EGF) recombinante humano na cicatrização da lesão do manguito rotador no ombro de coelhos. Métodos As rupturas do manguito rotador (RMRs) foram criadas experimentalmente em ambos os ombros de 20 coelhos Nova Zelândia. Os coelhos foram divididos nos seguintes grupos: RMR (grupo controle; n = 5), RMR + EGF (grupo EGF; n = 5), RMR + reparo transósseo (grupo reparo; n = 5) e RMR + EGF + reparo transósseo (grupo reparo combinado+ EGF; n = 5). Todos os coelhos foram observados por 3 semanas, e amostras de biópsias foram coletadas do ombro direito na 3ª semana. Após mais 3 semanas de observação, todos os coelhos foram submetidos à eutanásia, e uma amostra de biópsia foi coletada dos ombros esquerdos. Todo o material de biópsia foi corado com hematoxilina e eosina (H&E) para avaliação de vascularidade, celularidade, proporção de fibras e número de células fibrocartilaginosas à microscopia óptica. Resultados O grupo reparo combinado + EGF apresentou a maior quantidade e a sequência mais regular de colágeno. O grupo reparo e o grupo EGF apresentaram maior atividade fibroblástica e formação capilar em comparação ao grupo controle, mas a maior atividade fibroblástica e a formação capilar com maior vascularidade foram detectadas no grupo reparo combinado + EGF (p < 0,001). O EGF parece melhorar a cicatrização da ferida no reparo da RMR. A aplicação isolada de EGF, mesmo sem cirurgia reparadora, parece melhorar a cicatrização da RMR. Conclusão Além do reparo da RMR, a aplicação de EGF recombinante humano auxilia a cicatrização do manguito rotador dos ombros de coelhos.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

A case report on ofloxacin-induced Stevens–Johnson syndrome: Scorten-based approach

Stevens–Johnson syndrome (SJS) is a rare immune-mediated severe cutaneous adverse reaction with an incidence rate of 0.05–2 persons/million population/month. Drugs are the most commonly implicated in 95% of cases. In our report, a 52-year-old male patient presented with chief complaints of skin rashes over the body and was having a history of using a tab. ofloxacin for gastroenteritis. The severity of SJS was assessed using SCORTEN (=1). The drug can be considered as a probable/likely cause of adverse drug reaction as per causality assessment of the suspected adverse drug reactions. Early diagnosis helps the clinician to elude secondary infection and subsequent complications. It highlights the mandatory reporting of the offending drug and the necessity of pharmacovigilance in different countries.

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population

Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.

Prediction of EGFR mutant subtypes in patients with non-small cell lung cancer by pre-treatment CT radiomics and machine learning / 中华放射医学与防护杂志

Objective:To evaluate the feasibility and clinical value of pre-treatment non-enhanced chest CT radiomics features and machine learning algorithm to predict the mutation status and subtype (19Del/21L858R) of epidermal growth factor receptor (EGFR) for patients with non-small cell lung cancer (NSCLC).Methods:This retrospective study enrolled 280 NSCLC patients from first and second affiliated hospital of University of South China who were confirmed by biopsy pathology, gene examination, and have pre-treatment non-enhanced CT scans. There are 136 patients were confirmed EGFR mutation. Primary lung gross tumor volume was contoured by two experienced radiologists and oncologists, and 851 radiomics features were subsequently extracted. Then, spearman correlation analysis and RELIEFF algorithm were used to screen predictive features. The two hospitals were training and validation cohort, respectively. Clinical-radiomics model was constructed using selected radiomics and clinical features, and compared with models built by radiomics features or clinical features respectively. In this study, machine learning models were established using support vector machine (SVM) and a sequential modeling procedure to predict the mutation status and subtype of EGFR. The area under receiver operating curve (AUC-ROC) was employed to evaluate the performances of established models.Results:After feature selection, 21 radiomics features were found to be efffective in predicting EGFR mutation status and subtype and were used to establish radiomics models. Three types models were established, including clinical model, radiomics model, and clinical-radiomics model. The clinical-radiomics model showed the best predictive efficacy, AUCs of predicting EGFR mutation status for training dataset and validation dataset were 0.956 (95% CI: 0.952-1.000) and 0.961 (95% CI: 0.924-0.998), respectively. The AUCs of predicting 19Del/L858R mutation subtype for training dataset and validation dataset were 0.926 (95% CI: 0.893-0.959), 0.938 (95% CI: 0.876-1.000), respectively. Conclusions:The constructed sequential models based on integration of CT radiomics, clinical features and machine learning can accurately predict the mutation status and subtype of EGFR.

Analysis of clinical, pathological and CT features of epidermal growth factor receptor exon 19 and 21 mutations in lung adenocarcinoma / 中华放射学杂志

Objective:To investigate the clinical, pathological and CT characteristics of lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) 19 and 21 exon mutations.Methods:Clinical, pathological and imaging data of 683 patients with lung adenocarcinoma in the First Affiliated Hospital of Chongqing Medical University from December 2012 to December 2020 were retrospectively analyzed. According to the gene mutation status, patients were divided into EGFR common loci mutation group (exons 19 or 21) with 382 cases (mutation group), including 19 exon mutation in 165 cases (exon 19 mutation subgroup) and 21 exon mutation in 217 cases (exon 21 mutation subgroup), and EGFR negative mutation group with 301 cases (negative mutation group). Independent sample t-test and χ 2 test were used to compare those features between mutation group and negative mutation group, exon 19 mutation subgroup and exon 21 mutation subgroup. The indicators with statistically significant differences in univariate analysis were included in binary logistic regression analysis to screen out independent predictors and establish the model. Receiver operating characteristic curve and area under curve (AUC) were used to evaluate the predictive performance of the model or index. Results:There were significant differences between mutation group and negative mutation group in gender distribution, smoking history, the proportion of solid-dominated growth pattern, peripheral distribution, tumor maximum diameter (3 cm as the cut-off point) distribution, spiculation, ground-glass opacity (GGO), air bronchogram, vascular convergence sign, pleural retraction, the number of lung metastases (10 as the cut-off point), pleural effusion, necrosis, and lymph node metastasis in lung adenocarcinoma patients ( P<0.05). The logistic regression showed that female (OR=5.230,95%CI 3.534-7.740, P<0.001), non-smoking history (OR=2.970, 95%CI 1.986-4.443, P<0.001), GGO (OR=3.092, 95%CI 1.746-5.477, P<0.001), absence of necrosis (OR=1.754, 95%CI 1.047-2.939, P=0.033), vascular convergence sign (OR=3.129, 95%CI 1.971-4.969, P<0.001), pleural retraction (OR=2.434, 95%CI 1.680-3.526, P<0.001), and the number of lung metastases≥10 (OR=2.242, 95%CI 1.284-3.915, P=0.005) were independent predictors of EGFR exon 19 and 21 mutations, and the AUC of the logistic model based on these predictors in predicting EGFR exon 21 and 19 mutations in lung adenocarcinoma was 0.804. There were significant differences between EGFR exon 19 mutation subgroup and EGFR 21 mutation subgroup in gender distribution, the proportion of acinar-dominated growth pattern, peripheral distribution, vascular convergence sign, pleural retraction ( P<0.05). The logistic regression showed that vascular convergence sign (OR=1.833, 95%CI 1.187-2.831, P=0.006) was independent predictor of EGFR exon 21, the AUC of vascular convergence sign for distinguishing EGFR exon 19 and EGFR 21 mutation was 0.604. Conclusions:There are some differences in the clinical, pathological, and CT features of patients between EGFR common loci mutation and EGFR negative mutations, EGFR exon 19 and exon 21 mutations in lung adenocarcinoma. Familiarity with these differences is helpful for the individualized treatment of patients with unknown gene mutation status of lung adenocarcinoma.

Relationship Between p53， EGFR and Radiotherapy Resistance of Head and Neck Squamous Cell Carcinoma / 中山大学学报(医学科学版)

Head and neck cancers are the seventh most common type of cancer in the world， among which more than 90% are squamous cell carcinomas（HNSCC）. Radiotherapy is one of the important treatments for HNSCC， and the sensitivity of tumor cells to the therapy is a key factor influencing the efficacy of treatment. p53 is one of the most common mutated genes in HNSCC， and epidermal growth factor receptor（EGFR） is overexpressed in many HNSCC. Both of these genes could enhance cellular DNA repair， which may be related to the radiotherapy resistance of HNSCC. This review focuses on the mechanisms by which tumor cells escape radiation-mediated apoptosis through p53 and EGFR-mediated DNA repair.

Research progress of furmonertinib for EGFR-mutated non-small cell lung cancer / 中国药房

Lung cancer is mainly non-small cell lung cancer （NSCLC）. NSCLC is often associated with epidermal growth factor receptor （EGFR） gene mutations. Currently， epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） are the preferred first-line treatment option for EGFR-mutated NSCLC. Furmonertinib is the second third-generation EGFR-TKI marketed in China， which is developed independently by China. In this review， it is found that furmonertinib has dual activity， strong tumor suppression， high selectivity， and high safety profile， and is effective in the treatment of EGFR-sensitive mutation， EGFR exon 20 T790M resistance mutation， EGFR exon 20 insertion mutation， and central nervous system metastasis NSCLC， and its relevant clinical trials are only enrolled in Chinese patients， which is more guidance for Chinese NSCLC patients in China.

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.

USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.