摘要:Renal cell carcinoma (RCC) is one of the three major urinary system tumors. With the changes of lifestyle and the rise of obesity, hypertension and other diseases, the incidence of RCC is increasing. The onset of RCC is hidden, and RCC has strong heterogeneity. Most RCC patients are found accidentally by imaging examination, so many patients were diagnosed in the advanced stage. Although the emergence of targeted therapy and immunotherapy has greatly prolonged the survival time of patients with advanced RCC, due to many pathological types of RCC, it is still difficult for many patients to benefit from the systematic treatment. Many basic and clinical studies are devoted to the development of new targets or drugs to prolong the survival time of patients. This article reviewed the advances in the research, diagnosis and treatment of RCC in 2022.
关键词:Renal cell carcinoma;Immunotherapy;Targeted therapy;Basic research;Clinical research
摘要:Bladder cancer (BCa) is a common malignant tumor of the urinary tract. Significant progress has been made in both basic and clinical research on BCa, which has further elucidated the drivers of BCa development at the gene and protein levels, and explored the structure and interactions of the tumor microenvironment. The early diagnostic index nuclear matrix protein 22 (NMP22) of BCa has great clinical limitations, and new biomarkers are constantly being developed to make early diagnosis more accurate. A breakthrough has been made in the comprehensive treatment of BCa, including the combination of immune checkpoint inhibitor therapy on cisplatin-based first-line chemotherapy, the application of antibody-drug conjugate (ADC), and the combination of these drugs in different stages of BCa. In order to better describe the recently achieved research results, a review of the research progress of BCa in 2022 was presented.
摘要:About 40%-70% of newly diagnosed prostate cancer patients in China are in the stage of metastatic disease, and the spatio-temporal heterogeneity of the occurrence and development of prostate cancer and the unique metastasis pattern make it difficult to analyze immune markers based on biopsy tissue. With the advancement of many basic and clinical studies, new advances have been made in the pathogenesis, diagnostic methods, perioperative management, radiotherapy techniques and systematic treatment of advanced diseases of prostate cancer. These results continuously enrich the means of diagnosis and treatment of prostate cancer patients and improve their prognosis. Here was a review of the major advances in prostate cancer research in 2022.
摘要:Lung cancer remains the malignant tumor with the highest morbidity and mortality in China, among which non-small cell lung cancer (NSCLC) accounts for more than 80%. Clinical studies related to adjuvant immunotherapy and neoadjuvant immunotherapy in perioperative NSCLC have been updated. In terms of targeted therapy, the research and development of drugs for rare and difficult-to-treat targets continues to be hot, and the research and development of antibody-drug conjugate gradually becomes hot, which is expected to open a new track for the diagnosis and treatment of lung cancer. Rare target diagnosis and treatment of NSCLC has gradually entered an era of precision and standardization. In terms of immunotherapy for patients with advanced NSCLC, the new regimen of combined immunotherapy is expected to further improve the efficacy. This review, with the focus on advanced NSCLC, summarized the development of NSCLC, discussed current problems and challenges, and proposed prospects on future directions.
摘要:CD30 can be expressed in a variety of lymphoma subtypes, among which classical Hodgkin lymphoma (CHL) and anaplastic large cell lymphoma (ALCL) are the most common ones. Recently, Brentuximab vedotin, the antibody-drug conjugate targeting CD30, has been approved in the treatment of patients with refractory and relapsed CHL and ALCL, and has achieved significant curative effect. However, whether CD30-targeted therapy could benefit patients with other types of lymphoma remains largely unknown. Accurate evaluation of the expression level of CD30 may thus have important guiding significance for the clinical trials and individualized treatment of patients with those lymphomas. To date, CD30 detection is mainly via immunohistochemical staining, however, with no unified and standardized process and interpretation method. We herein described the current status on CD30 testing, and explored the procedures of immunohistochemical detection and interpretation of the results through multicentric studies. A consensus was finally reached, which was based on the combination of our research results, literature review, experts’ experience, and internal discussion among the panel members, and might hopefully contribute to standardization of the immunohistochemical detection and interpretation of CD30 expression in lymphomas.
关键词:Lymphoma;CD30;Immunohistochemistry;Standards for detection;Criteria for interpretation
摘要:Pancreatic cancer is a type of malignant tumor with high incidence and low survival rate. It is urgent to develop novel and efficient therapeutic means for patients lacking surgical indications and patients with poor effects of radiotherapy and chemotherapy. In recent years, antibody-drug conjugate (ADC) has become hot because of their high selectivity and anti-tumor activity. ADC has achieved some results in the treatment of pancreatic cancer, but still face many challenges. This article provided a brief review of the latest developments of ADC in pancreatic cancer in 2022.
关键词:Antibody-drug conjugate;Pancreatic cancer;Clinical research
摘要:Background and purpose: tRNA-derived fragments (tRF) are a kind of short non-coding RNA (14-30 nt) that influences the course of cancer. This study aimed to investigate the molecular pathways that might underlie the effects of tRF-Pro-CGG on the biological behavior of mouse pancreatic cancer cells. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to assess the expression of tRF-Pro-CGG in mouse pancreatic cancer cell lines pan02 and LTPA, human pancreatic cancer cell line Capan-2, and normal pancreatic cells HPDE6-C7. tRF-Pro-CGG overexpression in pan02 cells and LTPA cell suppression were achieved through lentiviral transfection, and RTFQ-PCR and Western blot were used to determine overexpression and knockdown effects. Cell counting kit-8 (CCK-8) was used to detect cell proliferation. Transwell assays were used to detect cell migration and invasion ability. The effect of tRF-Pro-CGG on the growth and metastasis of pancreatic cancer transplantation tumors in nude mice model was investigated. H-E staining was used to observe the histopathological structure of transplantation tumors. Western blot was used to detect the expression and phosphorylation of proliferation-related protein Ki-67 and metastasis-related proteins. Western blot was used to assess the expressions of cadherin, vimentin, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway protein and phosphorylation in transplanted tumor tissues. Results: tRF-Pro-CGG expression was lowest in the mouse pancreatic cancer cell line pan02. Both mRNA and protein expression levels of tRF-Pro-CGG were significantly increased (P <0.01) after transfection of tRF-Pro-CGG mimics in pan02 cells, and cell proliferation ability (P<0.01), cell migration (P<0.001) and invasion ability (P<0.001) were significantly reduced. A significant decrease in the volume (P<0.01) and weight (P<0.001) of transplanted tumors in nude mice was observed, and significant necrotic and apoptotic cells in transplanted tumor were identified. In transplanted tumor tissues of nude mice, the Ki-67 proliferatien index and expression of vimentin were significantly decreased (P<0.001), while E-cadherin was increased (P<0.001). The expressions of PI3K, P-PI3K, AKT and P-AKT were significantly decreased (P<0.001). There was no significant difference in the number of liver metastases from pancreatic cancer (P>0.05). The mouse pancreatic cancer cell line LTPA had the greatest level of tRF-Pro-CGG expression. The mRNA and protein expression levels of tRF-Pro-CGG were significantly reduced (P<0.01) after transfection of tRF-Pro-CGG inhibitor in LTPA cells. The proliferation ability of cells was significantly increased (P<0.01), the migration of cells (P<0.001) and invasive ability (P<0.001) were significantly increased. The volume (P<0.01) and weight (P<0.01) of transplanted tumors in nude mice were significantly increased, and a limited proportion of necrotic and apoptotic cells were seen in nude mice tumor tissues implanted. In the transplanted tumor tissues of nude mice, the Ki-67 proliferation index and expression of vimentin were significantly increased (P<0.001), while E-cadherin was decreased (P<0.001). The expressions of PI3K, P-PI3K, AKT, and P-AKT were significantly increased (P<0.001). There was no difference in the number of liver metastases from pancreatic cancer (P>0.05). Conclusion: Overexpression of tRF-Pro-CGG reduced pancreatic cancer cell proliferation, migration and invasion in mice, slowed the formation of pancreatic cancer transplanted tumors in nude mice, and decreased Ki-67 proliferation index and expression of vimentin and PI3K/AKT phosphorylation levels. The PI3K/AKT signaling pathway may be regulated by tRF-Pro-CGG, which may suppress the development of pancreatic cancer.
关键词:Pancreatic cancer;tRNA-derived fragments-Pro-CGG;Proliferation;Migration;Invasion;Tumor transplantation model in nude mice
摘要:Background and purpose: Aberrant N6-methyladenosine (m6A) modification caused by dysregulation of methyltransferase-like factor 14 (METTL14) plays an important role in the progression of various cancers, and it is unclear whether it is involved in the endometrial cancer (EC) progression. This study aimed to investigate the role of aberrant m6A modification caused by dysregulation of METTL14 in EC invasion and metastasis. Methods: Ninety-six EC patients who underwent curative surgery in Qinghai Provincial People’s Hospital from 2017 to 2021 were enrolled. RNA (70 pairs) or proteins (10 pairs) were isolated from frozen tissues for real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) or immunoblot analysis to assess METTL14 expression in EC. The expression of METTL14 and its correlation with clinicopathological features of EC were assessed. The biological effects of METTL14 in EC were determined in vitro and in vivo. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq), and following m6A dot blot, MeRIP-RTFQ-PCR, RIP-RTFQ-PCR or dual luciferase reporter assays were employed to screen and validate the candidate targets of METTL14. Results: The mRNA expression and protein levels of METTL14 were significantly downregulated in EC compared with matched adjacent tissues. Compared with the METTL14 high expression group, the METTL14 low expression group had a significant increase in International Federation of Gynecology and Obstetrics (FIGO) stage, infiltration depth, lymphovascular invasion, lymph node metastasis and the number of cases of tumor metastasis (P<0.05). Functionally, METTL14 inhibited the proliferation and invasive capacity of EC cells in vitro and in vivo. Mechanistically, METTL14-mediated demethylation of m6A resulted in post-transcriptional repression of estrogen receptor alpha (ERα). Furthermore, compared with METTL14, ERα induced oncogenic behavior of tumors. Conclusion: METTL14 attenuates ERα expression in EC cells in a m6A-dependent manner, thereby inhibiting tumor metastasis and invasion.
摘要:Background and purpose: The value of Vesical Imaging-Reporting and Data System (VI-RADS) based on multiparametric magnetic resonance imaging (MRI) in the preoperative assessment of bladder cancer muscle-invasive is increasingly recognized. However, there is still a high number of false positives when the diagnostic cut-off value is 3 points. Tumor size has certain auxiliary diagnostic value in the assessment of tumor infiltration. Therefore, this study mainly explored the diagnostic performance of VI-RADS combined with tumor size in assessing bladder cancer muscle-invasive. Methods: The preoperative bladder multiparametric MRI and clinical data of 119 patients with bladder cancer confirmed by surgery and pathology (a total of 159 lesions) who were treated in Fudan University Shanghai Cancer Center from November 2019 to February 2022 were retrospectively collected. VI-RADS score and tumor contact length (TCL) measurements were performed independently for each lesion by two radiologists. Lesions with differences in score or size were given consistent results following discussion by two physicians. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of VI-RADS, TCL and their combined models for muscle invasion, and the corresponding area under curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were compared. Results: Postoperative pathology confirmed that there were 75 and 84 lesions of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. The mean TCL of MIBC group (6.15-6.23 cm) was significantly different from that of NMIBC group (2.26-2.35 cm), and the difference was statistically significant (P<0.05). The specificity, PPV and diagnostic accuracy of VI-RADS combined with TCL in predicting bladder cancer muscle-invasive were significantly higher than those of VI-RADS with a diagnostic threshold of 3 points alone (P<0.05), whereas there was no statistically significant difference in the sensitivity and NPV (P>0.05). There was no significant difference in AUC between TCL (AUC = 0.89), VI-RADS (AUC = 0.90) and VI-RADS combined with TCL (AUC = 0.91) (P>0.05). Conclusion: VI-RADS combined with TCL can reduce the false positive rate of VI-RADS 3-point lesions in the evaluation of bladder cancer muscle-invasive to a certain extent, which is beneficial for avoiding overtreatment.
关键词:Vesical Imaging-Reporting and Data System;Tumor contact length;Muscle-invasive bladder cancer;Magnetic resonance imaging
摘要:Background and purpose: The standard treatment for patients with locally advanced esophageal cancer is neoadjuvant chemoradiotherapy (NCRT) plus radical resection. However, the technical aspects for implementing this comprehensive treatment strategy differ, especially in the controversial definition of the radiotherapy target area in NCRT. This study aimed to analyze the feasibility of involving field irradiation (IFI) in NCRT for locally advanced esophageal cancer. Methods: Retrospective analysis of locally advanced esophageal squamous cell carcinoma patients receiving NCRT in Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine from July 2016 to May 2017 showed that the radiotherapy target of all patients was our recommended IFI. The radiotherapy plan was redesigned for the enrolled patients according to the two traditional target delineation of elective node irradiation (ENI) and primary subclinical lesion irradiation (SLI). The dosimetric parameters of the three groups and the dose differences of organ at risk (OAR), such as lungs, heart and spinal cord, were compared, and the relationship between IFI Recurrence pattern and radiation target volumes was analyzed. Results: A total of 26 patients were enrolled. The average target volume of IFI was (277±77) cm3, which was significantly lower compared with ENI and SLI (P<0.05). IFI could significantly reduce relative volume fraction of lungs irradiated more than 5 and 20 Gy (V5 and V20), lungs average dose (Dmean), heart V30, heart Dmean and spinal cord maximum dose (Dmax) (P<0.05), compared with ENI. Lungs V20, lungs Dmean, heart Dmean and spinal cord Dmax decreased by 27.1%, 22.5%, 27.4% and 6.4% compared with ENI, and 24.1%, 22.0%, 24.8% and 5.7% compared with SLI, respectively. After 28 to 69 months of follow-up, 13 patients had recurrence and metastasis, of whom 7 patients had distant metastasis, 4 patients had recurrence in the irradiation field, and 1 patient had local recurrence in the irradiation field. The 3-year overall survival (OS) rate and disease-free survival (DFS) rate were 50.0% and 42.3%, respectively. Conclusion: IFI recommended by our institution is feasible to ensure clinical efficacy while significantly reducing the radiation dose of lungs, heart and spinal cord.
关键词:Esophageal squamous carcinoma;Neoadjuvant chemoradiotherapy;Target volume;Organ at risk;Dosimetry;Recurrence pattern
摘要:Background and purpose: In the design of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma, the traditional dose-volume (DV) physical optimization method is compared with the combined use of the DV physical optimization method and the generalized equivalent uniform dose (gEUD) optimization. This study aimed to investigate dosimetry differences in radiotherapy planning for nasopharyngeal carcinoma using gEUD method, to explore the effect of different optimization methods on the protection of organ at risk (OAR) in IMRT planning. Methods: Fifty patients with nasopharyngeal carcinoma in Eye & ENT Hospital of Fudan University from 2019 to 2021 were randomly selected, and two optimization plans were used for each case at the same time for optimization calculation. Group A used the traditional DV physical optimization method, while group B combined DV optimization and gEUD optimization methods adopted, in which gEUD was selected as a=1, 2, 5, 10 and 20. We evaluated the results of OAR dose data obtained by using different optimization schemes and different a values. Results: The planned data of the two plans were compared and analyzed, and there was no statistically significant difference in the dosimetry index of the target area between groups (P>0.05). However, in terms of the protection of the parotid gland and oral cavity, the results of the optimization plan of group B were significantly better compared with group A. The a value of gEUD had more obvious influence on the average dose of the parotid gland and the oral cavity. Conclusion: In the radiotherapy plan for nasopharyngeal carcinoma, the combined use of physical optimization and biological optimization can not only meet the target dose requirements but also better protect the parotid gland, oral cavity and other endangered OAR.
摘要:Background and purpose: The establishment of artificial pneumothorax during video-assisted thoracoscopic surgery may affect the intrathoracic pressure, cause the obstruction of superior vena cava reflux, and lead to the increased risk of adverse cardiovascular events during hospitalization. However, elderly patients with esophageal cancer are more likely to have adverse cardiovascular events during the perioperative period due to the significant decline in functional status, which seriously affects the rehabilitation process. This study aimed to investigate the influencing factors of cardiovascular adverse events risk in elderly patients with esophageal cancer undergoing video-assisted thoracoscopic surgery and construct nomograph model to guide the formulation of clinical intervention plan. Methods: Five hundred and forty-six elderly patients with esophageal cancer undergoing video-assisted thoracoscopic surgery who were treated in The First Hospital of Danjiangkou City were retrospectively chosen in the period from January 2015 to October 2020. All patients were grouped according to the occurrence of cardiovascular adverse events in perioperative period, the related clinical data were analyzed, and the independent influencing factors of cardiovascular adverse events were evaluated by logistic regression model. Based on the above factors, the nomogram prediction model was constructed and receiver operating characteristic (ROC) curve was drawn to evaluate the prediction efficiency of nomogram model. Results: Eighty-four cases (15.38%) had perioperative cardiovascular adverse events in all 546 patients. Univariate analysis showed that American Society of Anesthesiologists (ASA) grade, the number of clinical risk factors, the level of hemodynamic changes, the level of airway pressure and the level of central venous pressure (CVP) were all related to the occurrence of cardiovascular adverse events (P<0.05). Multivariate analysis showed that ASA classification, the number of clinical risk factors, the level of hemodynamic changes and CVP were the independent influencing factors of cardiovascular adverse events (P<0.05). The nomogram prediction model was constructed according to the independent influencing factors of cardiovascular adverse event risk confirmed by multivariate analysis. The area under curve (AUC) of above nomogram model for predicting the risk of cardiovascular adverse events was 0.88 (95% CI: 0.81-0.97), and the sensitivity and specificity were 87.26% and 91.60% respectively. Conclusion: The incidence of cardiovascular adverse events in elderly patients with esophageal cancer undergoing video-assisted thoracoscopic surgery is independently related to many factors, of which ASA grade >Ⅲ, number of clinical risk factors >3, hemodynamic change level ≥30%, airway pressure level >30 cm H2O and CVP level >20 cm H2O have higher risk. The nomogram model based on the above factors has good prediction efficiency and may guide the formulation of clinical intervention programs.
摘要:Triple-positive breast cancer (TPBC) refers to breast cancer with positive expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), accounting for 5%-10% of all pathological types of breast cancer. TPBC is a special subtype of Luminal B breast cancer, which can receive both endocrine therapy and targeted therapy. TPBC is a special subtype of Luminal B breast cancer, which can receive both endocrine therapy and targeted therapy. The current guidelines recommend that anti-HER2-targeted therapy combined with chemotherapy is the first choice for TPBC treatment. However, the pathological complete response rate of TPBC is lower than that of hormone receptor negative/HER2-positive breast cancer. Moreover, patients with estrogen receptor expression >30% benefit less from anti-HER2-targeted therapy combined with chemotherapy. With the advent of various anti-HER2 targeted drugs and the clinical application of cyclin-dependent kinase 4 and 6 inhibitors, the combination of targeted therapy and endocrine therapy becomes possible for highly selected patients. This article reviewed the research progress of TPBC endocrine therapy combined with targeted therapy.
关键词:Triple-positive breast cancer;Endocrine therapy;Targeted therapy
摘要:As a good in vitro research model, organoids are more and more widely used in the biomedical field. By developing self-assembled 3D structures using various tissue culture techniques, organoids can rebuild the high complexity of cells in the inherent structure of the organ, and are therefore unanimously used to study mechanisms regulating body development and disease, high-throughput drug screening, and personalized treatment and so on. To better recapitulate cell-to-cell interactions within the microenvironment, co-culture strategies have been extended to more cell types, and their rapid development offers broader prospects for organoids and paves the way for the treatment of human diseases and regenerative medicine. This review discussed the role of co-culture strategies in organoid generation, and focused on the application of various cellular components and microorganisms in organoid construction, thereby providing reference and help for scholars to construct and develop organoids with a higher degree of in vivo simulation.