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.

Advances in Salmonella-mediated targeted tumor therapy / 药学学报

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Prognostic significance of ?mmunhistochemical axl expression in pancreas ductal adenocarcinomas

Introduction and Aim: Pancreas Ductal Adenocarcinomas (PDACs) are among the leading causes of cancer-related death. Tyrosine kinase receptors (TKRs) are responsible for cell plasticity, chemoresistance, immunosuppression and metastasis potential. Axl is a receptor of the TKR family, and it has come to the fore in cancer treatment in the last decade. This study aimed to investigate the relationship of immunohistochemical Axl expression with histological features and its prognostic importance in PDACs. Materials and Methods: Fifty-three patients who were operated on for PDAC between 2006-2017 were evaluated retrospectively. Features of tumors; size, lymphovascular invasion (LVI), perineural invasion (PNI), resection margin (RM), lymph node metastasis (LNM), differentiation, tumor-infiltrating lymphocyte, stage and overall survival were recorded. Immunohistochemically, membranous and or cytoplasmic staining was considered positive for Axl. Statistically, Pearson Chi-Square, Cox regression and Kaplan Mayer tests were used in the SPSS 21.0 program. Results: Axl was positive in 28 patients (52.8%). Axl positivity was found to be associated with the presence of LVI (P = 0.009) and LNM (P = 0.002) and was an independent prognostic factor in short survival (P = 0.006). Conclusion: It was found that increased expression of Axl, which is known to increase EMT-mediated metastasis in carcinogenesis, may be an indicator of local spread and poor prognosis in PDAC patients. In this respect, it can be promising as a targeted molecule in PDAC patient's individualized treatments.

Early response to chemotherapy in children with Langerhans cell histiocytosis predicts long-term disease-free survival

Background: Langerhans cell histiocytosis (LCH) is a rare clonal malignancy of the monocyte-macrophage system. Patients with lesions in 搑isk organs� have significantly higher risk of mortality than patients with lesions limited to 搉on-risk� sites. The influence of early response to therapy on long-term survival in this heterogeneous multi-system disease was analyzed. Methods: During a 7-year period, we retrospectively analyzed the findings in 24 consecutive patients who required systemic chemotherapy for LCH [single system with multifocal bone involvement and multisystem involvement with or without risk organ (RO) involvement]. All patients were started on vinblastine and prednisolone. Progressive disease was treated with salvage protocols or targeted therapy. Positron emission tomography-computed tomography (PET-CT)/conventional CT based response assessment was performed at week 6 of chemotherapy, and if needed after week 12 of chemotherapy. Results: MFO bone, MS ROneg, and MS ROpos LCH was observed in 3, 4, and 17 patients, respectively. Age range of patients varied from 1 month�years (median = 18 months). The EFS and OS were 100% and 100% for MFO bone, 50% and 100%, respectively, for MS ROneg and 35% and 52%, respectively, for MS ROpos. OS was 93% and 100% for CR attained at 6 and 12 weeks respectively regardless of the risk status (P < 0.01). Conclusion: Rapid early response, that is, complete remission at 6 and 12 weeks was associated with significantly improved overall survival. In slow responders, early salvage with alternative regimens or targeted therapy may result in better outcomes

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.

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.

Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

Progressin Tumor-Associated Macrophages in the Treatment of Pancreatic Cancer / 中国医学科学院学报

Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy,and most of the patients are diagnosed in advanced stages.Because of limited available therapies,the mortality of this disease remains high.Tumor-associated macrophages(TAM),the main immune cells in the tumor microenvironment,are involved in the regulation of the occurrence and development of pancreatic cancer.Specifically,TAM are involved in the proliferation,invasion,immune escape,and chemoresistance of pancreatic cancer cells,demonstrating potential in the targeted therapy of pancreatic cancer.In this paper,we summarize the TAM-based therapies including consuming TAM,reprogramming TAM,dynamic imaging of TAM with nanoprobes,and regulating the phagocytic ability of TAM for pancreatic cancer,aiming to provide a theoretical basis for developing new therapies for pancreatic cancer.

Clinical efficacy of sequential surgery after immune and targeted therapy in downstaging initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

Review on non-surgical treatment for elderly patients with locally advanced head and neck squamous cell carcinoma / 中华放射肿瘤学杂志

With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

Research progress on recombinant human endostatin combined with radiotherapy and / or chemotherapy in the treatment of cervical cancer / 中华放射肿瘤学杂志

Cervical cancer is one of the most common malignant tumors in women worldwide. Locally advanced cervical cancer is mainly treated with radiotherapy and chemotherapy, but there are problems such as high recurrence rate and low survival rate. Bevacizumab, an angiogenic inhibitor that acts on vascular endothelial growth factor (VEGF), has been recommended by the National Comprehensive Cancer Network (NCCN) guidelines for the first-line treatment of recurrent / metastatic advanced cervical cancer in 2013. In recent years, the development of new targeted drugs for angiogenesis inhibitors, such as endostatin, has further optimized the new targeted therapy strategy for patients with locally advanced and advanced cervical cancer. Recombinant human endostatin (endostar) is a novel anti-angiogenesis drug independently developed by Chinese scientists. Although it has been applied in the treatment of cervical cancer, it needs to be further confirmed by high level evidence based medical evidence whether it can become a new option for targeted treatment of cervical cancer. In this article, clinical research progress on the treatment of cervical cancer by endostar combined with radiotherapy and / or chemotherapy was reviewed, aiming to provide reference for the optimization of cervical cancer treatment strategy.

The effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab for patients with inoperable esophageal squamous cell carcinoma / 中华放射医学与防护杂志

Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.

Research progress in characteristics of intestinal flora and intestinal flora-targeted therapeutic methods in patients with spinal cord injury / 中华创伤杂志

Patients with spinal cord injury is associated with seriously affected gastrointestinal function and imbalance of intestinal flora, leading to increased inflammation of spinal cord nerves. With the proposal of the theory of gut microbiota-gut-brain axis in recent years, the regulatory role of gut microbiota in the central nervous system and gastrointestinal system has gradually attracted attention. Although a considerable number of studies have focused on the effects of intestinal flora characteristics on spinal cord nerve function repair in patients with spinal cord injury from different perspectives, there are numerous research models for treating spinal cord injury with intestinal flora as intervention targets and remains a lack of unified and effective clinical treatment methods. In this paper, the authors review the research progress in characteristics of intestinal microflora and intestinal microflora-targeted therapeutic methods in patients with spinal cord injury, hoping to provide a reference for the clinical treatment and basic research of spinal cord injury.

Clinical status and research progress of primary pulmonary mucinous adenocarcinoma / 中国综合临床

Primary pulmonary mucinous adenocarcinoma is a subtype of lung adenocarcinoma, and its epidemiology is similar to other pulmonary adenocarcinoma. Because of its low incidence rate, the survival data of patients with pulmonary mucinous adenocarcinoma are few and often contradictory. KRAS mutations often occur in pulmonary mucinous adenocarcinoma, but EGFR mutations are rare. The expression of PD-L1 in pulmonary mucinous adenocarcinoma is very low. Patients with early pulmonary mucinous adenocarcinoma can benefit from surgery. Lobectomy is still the standard operation at present, but sub lobectomy may also be effective for early pulmonary mucinous adenocarcinoma. Other treatment options include platinum based dual drug chemotherapy, targeted therapy targeting driving genes, and the recent rise of immunotherapy. Future new targets and corresponding treatments should require more research to confirm.

Prospect on medical treatment of pulmonary mucinous adenocarcinoma / 中国综合临床

Pulmonary mucinous adenocarcinoma is a subtype of lung adenocarcinoma, among which invasive mucinous adenocarcinoma (IMA) is the most common subtype and is easily misdiagnosed as pneumonia. Its etiology and pathogenesis are unclear and may be related to gene mutations and other factors. Due to its relative rarity and few related studies, guidelines do not provide advices on its treatment. KRAS mutations are common in IMA patients, and Sotorasib may be effective against KRAS G12C mutated IMA. NRG1 fusion is considered to be an important driver of IMA, and afatinib may be effective in treating IMA with NRG1 fusion/rearrangement. PD-L1 expression is very low in IMA patients, while B7-H3 expression is high, so B7-H3 may be a potential immunotherapeutic target.

Research progress and clinical significance of the correlation between breast cancer heterogeneity and contrast-enhanced ultrasound / 中国医师杂志

Breast cancer is a highly heterogeneous tumor originating from genetic basis, with significant differences in morphology, immunophenotype and therapeutic response, which poses great challenges to the treatment of breast cancer patients. Therefore, it is very important to understand the diversity of different molecular biological states and expressions in tumor cells to obtain good therapeutic effects for breast cancer. Contrast-enhanced ultrasound (CEUS) is widely used as a non-invasive real-time diagnostic technique for breast tumors. At present, many domestic and foreign literatures have reported that there is a certain correlation between molecular biological indicators related to breast cancer and the characteristics of CEUS, which is expected to provide a reference for preoperative treatment through non-invasive and convenient ultrasound examination. The combination of ultrasound contrast agent and ultrasound can mediate the drug therapy of breast cancer, which makes the targeted delivery and targeted regulation of drugs possible, thus improving the efficiency of chemotherapy drugs. In this review, we reviewed the relationship between molecular markers related to breast cancer and CEUS and the application of ultrasound contrast agents in targeted therapy of breast cancer.

Clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer / 中国医师进修杂志

Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.

Efficacy of targeted drugs for metastatic non-clear cell renal cell carcinoma:a Meta-analysis / 现代泌尿外科杂志

【Objective】 To systematically evaluate the efficacy and safety of targeted drugs in the treatment of metastatic non-clear cell renal cell carcinoma (nccRCC) and to provide guidance for clinical treatment. 【Methods】 All observational studies and randomized controlled trials (RCTs) of nccRCC treated with targeted drugs were retrieved from the PubMed, Embase, the Cochrane Library and Web of Science. Three independent investigators screened the literature, extracted data and evaluated the quality of literature. The RCTs were evaluated using the Cochrane Handbook. One research with insufficient outcome data (follow-up bias) was assessed as high risk, and the other studies showed low or uncertain risk. The non-RCTs were evaluated with the JBI Quality Assessment Tool, and all studies displayed a low risk of bias. The data were analyzed with Stata 17.0 software. 【Results】 A total of 16 studies involving 989 patients were included. Meta-analysis showed that the objective response rate (ORR) was 12.6% (95%CI:8.1%-17.9%), the total disease control rate (DCR) was 65.3% (95%CI:58.3%-72.1%), the total median progression-free survival (PFS) was 5.80 (95%CI:4.69-6.91) months, and the median overall survival (OS) was 15.93 (95%CI:12.17-19.68) months. In subgroup analysis, the total ORR of patients with metastatic nccRCC treated with sunitinib and cabozantinib were 11.7% (95%CI:6.5%-18.0%) and 17.2% (95%CI:8.4%-28.2%), respectively. The total ORR of patients with papillary renal cell carcinoma was 9.1% (95%CI:2.4%-18.9%). 【Conclusion】 Targeted drugs have a significant effect on patients with metastatic nccRCC, but adverse reactions may occur. Targeted drugs have poor effects on metastatic papillary renal cell carcinoma, and cabozantinib may have greater survival benefits.

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.