Advances in molecular-targeted therapy for unresectable pancreatic cancer / 临床肝胆病杂志

Pancreatic cancer is one of the most prevalent malignant tumors of the digestive system， and its incidence and mortality rates are increasing year by year. Most patients with pancreatic cancer are unable to receive surgery due to the advanced stage. Although chemotherapy regimens based on gemcitabine and fluorouracil have prolonged the survival time of patients to some extent， some patients cannot tolerate chemotherapy and hence lose the opportunity for treatment. With the advent of the era of precision medicine， molecular-targeted therapy has exhibited an excellent therapeutic efficacy and has thus become one of the most important treatment techniques for tumors； however， due to the high heterogeneity of pancreatic cancer and its complicated tumor microenvironment， molecular-targeted therapy for pancreatic cancer has not achieved notable results. Therefore， it is imperative to seek new therapeutic targets and medications to overcome this issue. This article reviews the latest advances in the research on molecular-targeted therapy for unresectable pancreatic cancer based on common molecular targets and tumor immunity-related therapeutic targets， in order to provide new treatment strategies for patients with pancreatic cancer.

A molecular approach to triple-negative breast cancer: targeting the Notch signaling pathway

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Value of normalized apparent diffusion coefficient in predicting HER2 expression in bladder cancer / 现代泌尿外科杂志

【Objective】 To predict the expression of human epidermal growth factor receptor 2 (HER2) in urothelial bladder carcinoma based on normalized apparent diffusion coefficient (ADC). 【Methods】 The preoperative pelvic 3.0T magnetic resonance imaging (MRI) images of 127 patients with urothelial bladder carcinoma were retrospectively studied, the ADC was measured, and the HER2 expression in postoperative tissue specimens was determined with immunohistochemistry (IHC). The differences in normalized ADC were analyzed among different HER2 expressions and among different expression divisions. Correlation between normalized ADC and HER2 expression was analyzed. The optimal diagnostic threshold for distinguishing different expression divisions were determined with receiver operating characteristic (ROC) curve. 【Results】 Normalized ADC was negatively correlated with HER2 expression (tau-b=-0.180, P=0.008). Normalized ADC of HER2 overexpression group (IHC 2+, 3+) was lower than that of HER2 negative group (IHC 0, 1+) (P=0.081). Normalized ADC of HER2 expression group (IHC 1+, 2+, 3+) was significantly lower than that of HER2 zero-expression group (IHC 0) (P=0.020). Normalized ADC of HER2 strong positive group (IHC 3+) was significantly lower than that of HER2 non-strong positive group (IHC 0, 1+, 2+) (P=0.024). The optimal diagnostic threshold of HER2 strong positive group was 0.849; the sensitivity, specificity and accuracy were 0.621, 0.909 and 0.765, respectively. The optimal diagnostic threshold of HER2 overexpression group was 0.909; the sensitivity, specificity and accuracy were 0.547, 0.667 and 0.607, respectively. 【Conclusion】 Normalized ADC is negatively correlated with HER2 expression. ADC may be a potential marker for predicting HER2 expression.

Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma / 临床肝胆病杂志

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.

Efficacy of hepatic arterial infusion chemotherapy and its multimodality therapeutic regimens in treatment of patients with advanced hepatocellular carcinoma and related prognostic factors / 临床肝胆病杂志

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Research advances in tumor-associated macrophages in hepatocellular carcinoma microenvironment / 临床肝胆病杂志

Since there is a lack of obvious clinical symptoms in the early stage of hepatocellular carcinoma (HCC), most patients have progressed to the advanced stage at the time of confirmed diagnosis. There are limited treatment options for HCC patients who miss the opportunity for surgery, so it is of great importance to find new therapeutic targets. Tumor-associated macrophages (TAMs) are a group of macrophages existing in the tumor immune microenvironment and affect the malignant behaviors of HCC cells and the state of immune escape within the tumor. This article introduces the origin and classification of TAM, summarizes the role and mechanism of TAMs in vascular proliferation, invasion and metastasis, formation and maintenance of stemness, and anti-tumor immunity in HCC, and briefly describes the current research advances in therapeutic targets for TAM, and it is pointed out that targeting TAM may be a promising direction for clinical treatment.

Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Advances in macrophage-targeting nanoparticles for the diagnosis and treatment of inflammatory bowel disease / 浙江大学学报·医学版

The pathogenesis of inflammatory bowel disease (IBD) is not fully elucidated. However, it has been considered that inflammatory macrophages may be involved in the imbalance of the intestinal mucosal immunity to regulate several signaling pathways, leading to IBD progression. The ratio of M1 to M2 subtypes of activated macrophages tends to increase in the inflamed intestinal section. There are challenges in the diagnosis and treatment of IBD, such as unsatisfactory specificity of imaging findings, low drug accumulation in the intestinal lesions, unstable therapeutic efficacy, and drug-related systemic toxicity. Recently developed nanoparticles may provide a new approach for the diagnosis and treatment of IBD. Nanoparticles targeted to macrophages can be used as contrast agents to improve the imaging quality or used as a drug delivery vector to increase the therapeutic efficiency of IBD. This article reviews the research progress on macrophage-targeting nanoparticles for the diagnosis and treatment of IBD to provide a reference for further research and clinical application.

Progress of companion diagnostics in chimeric antigen receptor T-cell therapy / 白血病·淋巴瘤

Chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved good efficacy in treatment of hematological malignancies. As a precise and individualized treatment method, CAR-T is gradually moving towards commercialization. In addition to the introduction of corresponding policies and guiding principles, the related detection protocols should also be updated and improved to maximize its effect and achieve precise individualization. This article introduces and expands the concept of "companion diagnostics" that first appeared in targeted drugs, and introduces the significances of various detection technologies and biomarkers for patient screening, safety monitoring and evaluation of efficacy and CAR-T function in the whole process of CAR-T treatment.

Progress of minimal residual disease surveillance in B-cell lymphoma / 白血病·淋巴瘤

B-cell lymphoma is a group of heterogeneous hematologic malignant tumors originating from B cells, and it could be divided into invasive B-cell lymphoma and inert B-cell lymphoma. Currently, although disease remission rate has reached a high level, some patients still develop disease relapse or progression, thus, it is important to regularly monitor the disease and early identify the recurrence. At present, the recurrence of lymphoma mainly depends on imaging and clinical evaluation. However, some studies have shown that the minimal residual disease (MRD) monitoring based on flow or second-generation sequencing can provide a more accurate assessment of the depth of remission, predict the disease prognosis, and identify the early disease recurrence. This review summarizes the application of MRD in indolent lymphoma and aggressive lymphoma, mainly including the detection methods of MRD, research status and the application prospect of MRD in different lymphomas.

Progress of gene alterations and molecular typing of peripheral T-cell lymphoma / 白血病·淋巴瘤

Peripheral T-cell lymphoma (PTCL) is a group of heterogeneous malignant tumors with poor prognosis, with a lack of standard treatment regimen and poor efficacy of traditional chemotherapy. Therefore, finding new and more effective therapeutic targets to improve the efficacy of PTCL is an urgent clinical problem. In recent years, as the exploration of PTCL at the genetic and molecular levels has intensified, novel therapeutic targets based on gene alterations and molecular typing have been identified. This article summarizes the research progress of main gene alterations and molecular typing of PTCL in recent years.

Diagnosis and treatment progress of primary central nervous system lymphoma / 白血病·淋巴瘤

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma type. The prognosis of PCNSL patients after treated by traditional therapy regimen is very poor. The way to evaluate the prognosis of PCNSL and to increase therapeutic efficacy have become the clinical problem. The 64th American Society of Hematology (ASH) annual meeting reported the latest research progress of diagnosis and treatment of PCNSL, including image examination, genetic sequencing, targeted therapy, chimeric antigen receptor T-cell (CAR-T) therapy and autologous hematopoietic stem cell transplantation (ASCT). This paper reviews the latest progress of PCNSL in the 64th ASH annual meeting.

Progress of small molecule targeted therapy for acute myeloid leukemia / 白血病·淋巴瘤

Acute myeloid leukemia (AML) is the most common subtype of acute leukemia in adults with significant heterogeneity. Among hematological malignancies, targeted therapy for AML comes relatively late. Although traditional chemotherapy is still an indispensable part of AML treatment, more and more small molecule targeted drugs have been used in recent years since 2017. This article reviews the progress of small molecule targeted drugs for AML at the 64th American Society of Hematology annual meeting.

Treatment progress of relapsed/refractory follicular lymphoma / 白血病·淋巴瘤

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. The outcome of relapsed/refractory FL patients after multi-therapy is poor. The 64th American Society of Hematology annual meeting in 2022 announced the latest updates on relapsed/refractory FL, including targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell. This review provides an overview of these updates.

A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma / 医学前沿

The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.

Tra2β Enhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer / 生物医学与环境科学（英文）

OBJECTIVE@#In this study, the role and potential mechanism of transformer 2β (Tra2β) in cervical cancer were explored.@*METHODS@#The transcriptional data of Tra2β in patients with cervical cancer from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases were investigated. The functions of Tra2β were evaluated by using Western blot, MTT, colony formation, Transwell assays, and nude mouse tumor formation experiments. Target genes regulated by Tra2β were studied by RNA-seq. Subsequently, representative genes were selected for RT-qPCR, confocal immunofluorescence, Western blot, and rescue experiments to verify their regulatory relationship.@*RESULTS@#The dysregulation of Tra2β in cervical cancer samples was observed. Tra2β overexpression in Siha and Hela cells enhanced cell viability and proliferation, whereas Tra2β knockdown showed the opposite effect. Alteration of Tra2β expression did not affect cell migration and invasion. Furthermore, tumor xenograft models verified that Tra2β promoted cervical cancer growth. Mechanically, Tra2β positively regulated the mRNA and protein level of SP1, which was critical for the proliferative capability of Tra2β.@*CONCLUSION@#This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo, which provides a comprehensive understanding of the pathogenesis of cervical cancer.

É possível prever a mortalidade molecular em meduloblastomas pela análise dos receptores de membrana CD114? / Is it possible to predict molecular mortality in meduloblastomas by analysis of CD114 membrane receptors?

Introdução: Os meduloblastomas são os tumores sólidos mais comuns da infância e classificados em 4 subgrupos moleculares: WNT, SHH, grupo 3 e grupo 4. Muitos estudos buscam desenvolvimento de novos quimioterápicos para os meduloblastomas através da identificação de genes cuja expressão sejam novos alvos moleculares para drogas, como receptores de membrana associados a replicação celular. Objetivo: Avaliar a associação da expressão de CD114 com a mortalidade de pacientes portadores de meduloblastoma. Métodos: Revisão feita colhendo informações publicadas em plataformas virtuais em português e inglês. Inicialmente foi realizada busca por descritores relacionados ao tema - neurocirurgia, oncologia cirúrgica, terapia de alvo molecular e meduloblastoma - e seus equivalentes em inglês - neurosurgery, surgical oncology, molecular targeted therapy e medulloblastoma - com busca AND ou OR, considerando o título e/ou resumo. Após, foram incluídos somente os que tinham maior relação ao tema, e realizada a leitura da íntegra dos textos. Finalmente foram referidos 2 artigos. Resultados: Há diferença na expressão do receptor de membrana CD114 entre o Grupo 3 e os demais grupos moleculares, além de diferença entre o subtipo molecular SHH γ e os subtipos moleculares Grupo 3 α e Grupo 3 ß. Não houve diferença estatisticamente significativa entre os demais grupos e subtipos. Em relação à mortalidade, esta revisão não demonstrou significância estatística na relação entre expressões baixas e elevadas desse gene e a mortalidade. Conclusão: Não há relação direta entre a expressão do receptor de membrana CD114 e a mortalidade em pacientes portadores de meduloblastoma. Entretanto, são necessários estudos adicionais sobre as vias de sinalização intracelulares associadas a esse receptor e ao seu gene, o CSF3R.

Introduction: Medulloblastomas are the most common solid tumors of childhood and classified into 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Many studies seek to develop new chemotherapy drugs for medulloblastomas by identifying genes whose expression is new molecular targets for drugs, such as membrane receptors associated with cell replication. Objective: To evaluate the association of CD114 expression with mortality in patients with medulloblastoma. Methods: Review carried out collecting information published on virtual platforms in Portuguese and English. Initially, a search was carried out for descriptors related to the topic - neurosurgery, surgical oncology, molecular targeted therapy and medulloblastoma, with AND or OR search, considering the title and/or summary. Afterwards, only those that were most related to the topic were included, and the texts read in full. Finally, 23 articles were referred. Results: There is a difference in the expression of the CD114 membrane receptor between Group 3 and the other molecular groups, in addition to a difference between the SHH γ molecular subtype and the Group 3 α and Group 3 ß molecular subtypes. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this review did not demonstrate statistical significance in the relationship between low and high expressions of this gene and mortality. Conclusion: There is no direct relationship between the expression of the CD114 membrane receptor and mortality in patients with medulloblastoma. However, additional studies are needed on the intracellular signaling pathways associated with this receptor and its gene, CSF3R.

Estrategias terapéuticas actuales en el tratamiento del cáncer de ovario

Introducción: El cáncer de ovario es uno de los tumores más frecuentes y letales entre las mujeres. Esto se debe a su detección en estados tardíos y al desarrollo de quimiorresistencia a la terapia estándar. El desarrollo de terapias dirigidas contra las propiedades distintivas de las células cancerosas y sus características habilitadoras ha surgido como una alternativa promisoria para el tratamiento de estos tumores. Objetivo: Describir las actuales estrategias terapéuticas dirigidas contra las distintas capacidades de las células tumorales en el tratamiento del cáncer de ovario. Método: Se realizó una búsqueda en las bases de datos ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL´s CLIN, Registro Público Cubano de Ensayos Clínicos, entre enero y abril de 2023. Se seleccionaron 50 artículos referentes al cáncer de ovario y las alternativas para su tratamiento. Desarrollo: Se mencionaron los diversos factores que influyen en la elección de terapias contra el cáncer de ovario. Se describieron las actuales dianas terapéuticas utilizadas en el tratamiento de esta neoplasia, así como el empleo de múltiples fármacos aprobados y en fases de estudio, y las combinaciones sinérgicas de los mismos. Consideraciones finales: Actualmente existen disímiles opciones de tratamiento del cáncer de ovario. A pesar de que la eficacia clínica de los agentes dirigidos todavía está restringida a subtipos moleculares específicos y ningún ensayo ilustra un beneficio en la supervivencia general, son notorios los resultados alcanzados en el desarrollo de fármacos específicamente dirigidos contra la inestabilidad del genoma y angiogénesis sostenida.

Introduction: Ovarian cancer is one of the most common and lethal tumor in women. This happens as a result of late-stage cancer detention and an increased chemoresistance to standard therapy. The current development in therapies to kill the cancer cells and its spread tendencies has emerged as a key alternative to treat tumors. Objective: To describe the current therapeutic strategies lead to confront different capabilities of tumor cells found in the ovarian cancer treatment. Method: A search of literuture was carried out in the following databases ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL's CLIN, Cuban Public Registry of Clinical Trials, from January to April 2023. A total of 50 text concerning ovarian cancer subject and alternative for treatment were selected. Development: The driving factors that promoted the use of ovarian cancer therapies were pointed out. The current therapeutic targets used in the treatment of this neoplasia were described, as well as the use of multiple approved drugs or in process of approval, including the synergistic drug combinations. Final considerations: There are a lot of options currently being implemented in ovarian cancer treatment. Despite clinical efficacy of targeted therapy, it´s presented still restricted to specific molecular subtypes and none of the assays illustrated survival benefit in general; the results obtained in the process of drugs development specifically targeting genome instability and sustained angiogenesis have been remarkable.

Introdução: O câncer de ovário é um dos tumores mais frequentes e letais entre as mulheres. Isso se deve à sua detecção em estágios tardios e ao desenvolvimento de quimiorresistência à terapia padrão. O desenvolvimento de terapias direcionadas contra as propriedades distintas das células cancerígenas e suas características facilitadoras surgiu como uma alternativa promissora para o tratamento desses tumores. Objetivo: Descrever as atuais estratégias terapêuticas dirigidas contra as diferentes capacidades das células tumorais no tratamento do câncer de ovário. Método: Foi realizada uma busca nas bases de dados ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL's CLIN, Registro Público Cubano de Ensaios Clínicos, entre janeiro e abril de 2023. 50 artigos referentes ao câncer de ovário e as alternativas para o seu tratamento. Desenvolvimento: Foram mencionados os vários fatores que influenciam a escolha das terapias contra o câncer de ovário. Foram descritos os atuais alvos terapêuticos utilizados no tratamento desta neoplasia, bem como o uso de múltiplas drogas aprovadas e em fase de estudo, e suas combinações sinérgicas. Considerações finais: Atualmente existem opções de tratamento dissimilares para o câncer de ovário. Apesar de a eficácia clínica dos agentes direcionados ainda estar restrita a subtipos moleculares específicos e nenhum ensaio mostrar benefício na sobrevida global, são notáveis os resultados alcançados no desenvolvimento de fármacos direcionados especificamente contra a instabilidade do genoma e a angiogênese sustentada.

Role of new potential immune blocking molecules in the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world. The emergence of immune checkpoint inhibitors targeting programmed death-1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen-4 has brought great breakthroughs in the treatment of HCC. However, since HCC is a type of tumor with high heterogeneity, monotherapy is only effective for a small number of patients and may not be able to achieve long-lasting benefits due to drug resistance, and therefore, it is necessary to explore the potential of new immune checkpoint inhibitors in the prevention and treatment of HCC. This article analyzes and summarizes the biological characteristics of the new immune checkpoints T cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and B7 homologous protein-4 (B7-H4) and their expression and function in HCC. The analysis shows that TIGIT, VISTA, BTLA, and B7-H4 are highly expressed in HCC tissue and are associated with the prognosis of HCC patients, and targeted blocking of corresponding pathways can effectively inhibit the progression of HCC, suggesting that these molecules are potential targets for tumor treatment and that in-depth studies can provide new directions for HCC immunotherapy.