Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

As one of the most common malignant tumors, lung cancer poses a serious threat to human life and health. The platinum-based drug cisplatin (DDP) is used as the first-line treatment for lung cancer. The poor prognosis of lung cancer is mostly due to developed resistance to cisplatin, which poses a serious treatment challenge. The mechanism of cisplatin resistance is complex and unclear. Numerous studies have shown that DNA methylation plays a crucial role in the emergence of lung cancer cisplatin resistance. DNA hypermethylation results in the deactivation of numerous drug resistance genes and tumor suppressor genes through a change in chromatin conformation. Finding new therapeutic targets and indicators to predict the therapeutic effect can be aided by elucidating the complex mechanism. In order to discover novel strategies to overcome cisplatin resistance in lung cancer, this paper discusses DNA methylation-mediated cisplatin resistance and offers an overview of current demethylation procedures.
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Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

To explore the expression pattern and clinical significance of Integral membrane protein 2A（ITM2A） in drug resistant patients with chronic myeloid leukemia (CML).

Objective: To investigate the clinical characteristics and related risk factors of thyroid gland injury (TGI) in patients with a malignant tumor treated with a programmed death-1 (PD-1) inhibitor. Methods: A Retrospective case-control study. Data from 198 patients with a malignant tumor who received treatment with a PD-1 inhibitor in Chinese PLA General Hospital from October 2019 to October 2021 were collected and analyzed retrospectively. According to the TGI incurred after receiving treatment with a PD-1 inhibitor, patients were divided into a thyroid gland normal (TGN) group and TGI group. The prevalence, type, time of occurrence, and outcome of TGI were analyzed. The risk factors that may contribute to TGI were analyzed further by logistic regression. Results: TGI prevalence was 29.8% (59/198 cases) after treatment with a PD-1 inhibitor. There were significant differences with respect to previous radiotherapy and targeted therapy between the TGN group and TGI group (P<0.01 for both), but there were no significant differences with regard to sex, age, tumor type, previous surgery, previous chemotherapy, tumor metastasis, or type of PD-1 inhibitor (P>0.05 for all). Patients in the TGI group included those with subclinical hypothyroidism (32.2%, n=19), hypothyroidism (27.1%, n=16), thyrotoxicosis (23.7%, n=14), subclinical thyrotoxicosis (10.2%, n=6), and thyroiditis with normal thyroid function (6.8%, n=4), and the median time of occurrence (months) was 3.00, 3.00, 1.50, 1.50, and 0.80 after treatment with a PD-1 inhibitor, respectively. Among 20 patients who presented initially with thyrotoxicosis or subclinical thyrotoxicosis, 12 cases developed hypothyroidism or subclinical hypothyroidism subsequently. Logistic regression analysis suggested that previous radiotherapy (OR=3.737, 95%CI 1.390-10.046), targeted therapy (OR=3.763, 95%CI 1.553-9.117), thyroglobulin antibodies at baseline (OR=12.082, 95%CI 1.199-121.775), and thyroid-peroxidase antibodies at baseline (OR=10.874, 95%CI 1.010-117.047) were risk factors associated with the TGI caused by treatment with a PD-1 inhibitor. Conclusions: After treatment with a PD-1 inhibitor, TGI prevalence was high, especially in those with hypothyroidism or subclinical hypothyroidism. Some patients had a transition from thyrotoxicosis to hypothyroidism. Patients who underwent radiotherapy previously, had targeted therapy, or were thyroid autoantibody-positive at baseline may carry an increased risk of TGI following treatment with a PD-1 inhibitor.

Objective: To investigate the clinical significance and pathogenesis of heterogeneous nuclear ribonucleoprotein U (hnRNP U) in acute myeloid leukemia (AML) . Methods: The expression of hnRNP U, an RNA binding protein, in patients with AML and healthy controls was compared based on the Gene Expression Profiling Interactive Analysis database and the data of the center. The Beat AML Dataset (n=158) was downloaded from the cBioPortal database. The hnRNP U expression level was divided into the high-expression group (n=89) and low-expression group (n=69) , and patients' clinical characteristics were compared. The effect of hnRNP U on the biological behavior of human AML cell lines was studied by Cell Counting Kit-8 assay to detect cell proliferation. Annexin Ⅴ-APC/7-AAD antibodies were used to detect cell apoptosis. DNA content (PI staining) was quantitatively analyzed to detect cell cycle changes, and colony formation experiments were performed to detect cell cloning formation ability after hnRNP U knockdown in Kasumi-1 and MOLM-13 cells. To study the effect of hnRNP U knockdown on the DNA damage response (DDR) pathway proteins of cleaved-PARP, immunoblot analysis using p-H2A.X was conducted. Results: ①Pan-cancer analysis showed that hnRNP U was highly expressed in patients with AML, and the expression level of hnRNP U mRNA in peripheral blood mononuclear cells was significantly higher in patients with AML than in healthy controls (0.0315±0.0042 vs 0.0195±0.0006, respectively, P<0.01) . ②The age of onset was 56 (2-87) years in the high-expression group and 65 (8-85) years in the low-expression group (t=-2.681, P=0.007) . Moreover, the high-expression group had a higher proportion of combined FLT3 mutations than the low-expression group (χ(2)=4.069, P=0.044) . ③Compared with the negative control, hnRNP U knockdown inhibited the proliferation (P<0.001 and P<0.001) , promoted the apoptosis (P<0.01 and P<0.001) , decreased the colony formation ability (P<0.001 and P<0.001) , and arrested the cell cycles in the G(2)/M phase (P<0.05 and P<0.01) of Kasumi-1 and MOLM-13 cells, respectively. ④hnRNP U knockdown could increase the protein expression of cleaved-PARP and p-H2A.X on the DDR pathway. Conclusion: hnRNP U is highly expressed in AML, and hnRNP U knockdown can inhibit the occurrence and development of AML possibly through the activation of the DDR pathway.

To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula.

The clinical data of ten patients with immune checkpoint inhibitor-related type 1 diabetes mellitus were enrolled in the Second Xiangya Hospital of Central South University from January 2020 to October 2022 including 9 males and 1 female, with an average age of (57±8) years. There were 7 cases of fulminant type 1 diabetes and 3 cases of acute type 1 diabetes. Among the 10 patients, there were 5 cases of lung cancer, 2 cases of esophageal cancer, 1 case of gastric carcinom, 1 case of renal cell carcinoma, and 1 case of nasopharyngeal cancer. The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. Among them, 8 patients had diabetic ketoacidosis (DKA), 1 patient had ketosis, and 1 case had no ketosis at onset; 9 patients were negative for diabetes-related antibodies, and 1 patient was positive. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy.

Objective To investigate the effect of Achyranthes bidentata polysaccharides (ABPS) on adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its mechanism. Methods Five SD rats were sacrificed, and the BMSCs were dissected and isolated. The BMSCs were adherently cultured to logarithmic growth phase after identification, and treated with different doses of ABPS for 48 hours. The cell survival rates were detected by MTT assay. The highest dose of ABPS without toxicity to BMSCs was selected for subsequent experiments. Cells were randomly divided into control group, ABPS group, rosiglitazone group and ABPS combined with rosiglitazone group. Cell survival rates were detected by MTT assay. Triglyceride (TG) levels in BMSCs were detected by spectrophotometry. Lipid droplet formation in BMSCs was observed by oil red O staining. The mRNA and protein expression of peroxisome proliferater-activated receptor γ (PPARγ), transient receptor potential vanilloid 4 (TRPV4) and CCAAT/enhancer binding protein α (C/EBPα) were detected by real time quantitative PCR and Western blot analysis. Results The dose of ABPS≤200 mg/L had no obvious toxic effect on the growth of BMSCs after 48 hours, and the cell survival rate of 400 mg/L ABPS group was lower. Compared with the control group, the ABPS group showed decreased levels in TG, decreased relative expression of PPARγ, TRPV4 and C/EBPα mRNA and protein, and the decreased number of cytoplasmic lipid droplets. In the rosiglitazone group, observation reported the decreased cell survival rate, increased TG level, increased relative expression levels of PPARγ, TRPV4 and C/EBPα mRNA and protein, along with the increased number of cytoplasmic lipid droplets. Compared with the ABPS group, the cell survival rate was decreased, TG level was increased, the relative expression levels of PPARγ, TRPV4 and C/EBPα mRNA and protein increased, and the number of cytoplasmic lipid droplets increased in the ABPS combined with rosiglitazone group. Compared with rosiglitazone group, the survival rate was increased, TG level was decreased, the relative expression levels of PPARγ, TRPV4 and C/EBPα mRNA and protein were decreased, and the number of cytoplasmic lipid droplets was decreased in the ABPS combined with rosiglitazone group. Conclusion ABPS can inhibit adipogenic differentiation of BMSCs, and the mechanism may be related to the regulation of PPARγ/TRPV4 pathway.

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

This study aims to investigate the effect of ethoxysanguinarine(Eth) on cisplatin(DDP)-resistant human gastric cancer cells and decipher the underlying mechanism. The human gastric cancer cell line SGC7901 and the DDP-resistant cell line SGC7901/DDP were used as the cell models. Western blot was employed to determine the expression levels of multidrug resistance-related proteins, and methyl thiazolyl tetrazolium(MTT) assay to detect the proliferation of SGC7901 and SGC7901/DDP cells exposed to DDP. After treatment with different concentrations of Eth, the proliferation of SGC7901 and SGC7901/DDP cells was detected by MTT assay, trypan blue exclusion assay, colony formation assay, and high-content imaging and analysis system. The apoptosis of SGC7901/DDP cells was detected by flow cytometry with Annexin V-FITC/PI staining. GFP-LC3 transfection was carried out to detect the effect of Eth on the autophagy of SGC7901/DDP cells. The expression levels of the multidrug resistance-related protein P-glycoprotein(P-gp), the apoptosis-related proteins [caspase-9, caspase-3, and poly(ADP-ribose) polymerase(PARP)], the autophagy-related protein light chain 3-Ⅱ(LC3-Ⅱ), the key effectors [mammalian target of rapamycin(mTOR), 70 kDa ribosomal protein S6 kinase(P70 S6 K), and 4 E binding protein 1(4 E-BP1)] of the mammalian target of rapamycin complex 1(mTORC1) signaling pathway, cancerous inhibitor of protein phosphatase 2A(CIP2A), and protein kinase B(Akt) were measured by Western blot. The mRNA level of CIP2A in the SGC7901/DDP cells exposed to Eth for 24 h was analyzed by RT-qPCR. After SGC7901/DDP cells were transfected with CIP2A expression vector pcDNA3.1-HA-CIP2A and treated with different concentrations of Eth, MTT assay was used to determine the prolife-ration of SGC7901/DDP cells and Western blot to detect the expression levels of related proteins. The interaction sites of Eth and CIP2A were predicted by molecular docking. The affinity between Eth and CIP2A was determined by drug affinity responsive target stability(DARTS) assay. The pharmacokinetic properties and drug-like activity of Eth were predicted by SwissADME. The results indicated that SGC7901/DDP cells were more sensitive to Eth than SGC7901 cells. Eth significantly inhibited proliferation and colony formation and changed the morphology, roundness, and area of SGC7901/DDP cells. Eth treatment caused the nucleus shrinking and significantly increased the apoptosis rate of the cells. Furthermore, Eth down-regulated the expression of caspase-9 and caspase-3 precursors and promoted the cleavage of PARP, which suggested that Eth induced the apoptosis of SGC7901/DDP cells. The GFP-LC3 in Eth-treated cells showed speckled aggregation. The up-regulated expression of LC3-Ⅱ by Eth indicated that Eth activated the autophagy of SGC7901/DDP cells. Eth down-regulated the expression of P-gp, the phosphorylation of mTOR, P70 S6K, and 4E-BP1, the expression of CIP2A, and the phosphorylation of Akt. Additionally, it increased the activity of PP2A, and had no significant effect on the expression of CIP2A in SGC7901/DDP cells. CIP2A overexpression antagonized the inhibition of cell proliferation and the activation of autophagy by Eth. Molecular docking suggested that Eth bound to CIP2A. The results of DARTS assay further proved the above binding effect. Eth has potential drug-like activity. The above results demonstrated that Eth inhibited the proliferation, induced the apoptosis, and activated the autophagy of SGC7901/DDP cells by targeting CIP2A and then down-regulating PP2A/mTORC1 signaling pathway. This study provided a new target for the treatment of cisplatin-resistant gastric cancer.

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.

To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence.

Abnormal cell apoptosis is closely related to the occurrence of hematologic tumors, B-cell lymphoma-2 (BCL-2), as a key anti-apoptotic protein in intrinsic programmed cell death, has become a hot spot in the treatment of hematologic tumors in recent years. Venetoclax is an oral small-molecule selective BCL-2 inhibitor approved by the Food and Drug Administration (FDA） for the treatment of chronic lymphocytic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) patients and for the treatment of elderly acute myeloid leukemia (AML) patients that is not suitable for aggressive chemotherapy. In addition, it also showed a promising clinical application in treatment of non-Hodgkin's lymphoma (NHL) patients, which is a new expansion of the clinical indications for venetoclax. In this review, the role of BCL-2 protein family played in the regulation of NHL cell apoptosis, the development of BCL-2 inhibitors and the recent research progress of venetoclax in the treatment of NHL are reviewed.

To investigate the effect of dihydroartemisinin (DHA) combined with arsenic trioxide (ATO) on the viability and apoptosis of acute myeloid leukemia (AML) FLT3-ITD mutant cell line MOLM13 and its mechanism.

Neurologic immune-related adverse events (NAEs) are rare complications of immune checkpoint inhibitors (ICI). NAEs can affect the central nervous system, peripheral nervous system and neuroendocrine system, they can lead to death and serious dysfunction. NAEs requires standardized diagnosis, treatment and clinicians' high attention. The diagnosis of NAEs is very challenging due to its complexity, diversity and some non-specific clinical manifestations. It needs to be carefully distinguished from neurological dysfunction caused by other diseases such as tumor, infection, metabolism and iatrogenic (non-immune mediated) complications. Therefore, Committee of Neoplastic Supportive-Care of China Anti-Cancer Association and Cancer Clinical Chemotherapy Committee of China Anti-Cancer Association organized experts to conduct literature analysis and evidence level discussion on the clinical key issues related to NAEs, including the epidemiology, pathogenesis, risk factors, general principles of diagnosis and treatment, clinical manifestations and diagnosis and treatment strategies of specific types of NAEs, and the principles of ICI rechallenge after NAEs. Based on the latest clinical evidence and combined with China's clinical practice, the expert committee finally formulated a Chinese expert consensus on diagnosis and treatment of nAEs (2022 edition) for the prevention, diagnosis, comprehensive treatment and follow-up of NAEs.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem and challenging for oncologists. CIPN is often a persistent adverse consequence of certain chemotherapeutic agents and more cancer survivors will experience CIPN leading to chronic pain and worsening quality of life. However, the available and effective strategies for clinical treatment of CIPN are very limited. Oncologists are frequently obliged to decrease or stop neurotoxic anticancer drugs, with a possible deleterious impact on the oncological prognostic. The challenges faced by CIPN include further study on the pathological mechanism, dose threshold, incidence, risk factors and clinical characteristics of CIPN; lack of diagnostic criteria and tools of CIPN; lack of effective and standardized CIPN prevention and treatment programs. The current update of research results on these challenging issues of CIPN will provide more decision-making evidence for oncologists to diagnose and treat CIPN. Therefore, Committee of Neoplastic Supportive-Care of China Anti-Cancer Association and Cancer Clinical Chemotherapy Committee of China Anti-Cancer Association convenes some experts to summarize the recent literatures and discuss to reach the consensus about recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of CIPN.

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.

Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.