Objective:To analyze the clinical characteristics of immune-related psoriasis caused by immune checkpoint inhibitors (ICIs).Methods:The patients with newly developed or worsening psoriasis after ICIs treatment in Department of Oncology, the Affiliated Hospital of Qingdao University from November 2019 to October 2023 were enrolled in this study. The patients′ gender, age, tumor type and stage, usage and dosage of ICIs, drugs applied in combination, history of psoriasis, the time of new onset or deterioration, clinical manifestations, intervention measures and outcomes were collected, and descriptive statistical analysis was performed.Results:A total of 13 patients were enrolled in the study, including 10 males and 3 females, with a median age of 66 years. The primary diseases included lung cancer (in 7 patients), gastric cancer (in 5 patients), and cholangiocarcinoma (in 1 patient). The tumor stage was Ⅳ in 12 patients and Ⅲ in 1 patient. Ten patients were treated with programmed cell death 1 receptor (PD-1) inhibitors, 2 with programmed cell death ligand 1 (PD-L1) inhibitors, and one with a PD-1/cytotoxic T-lymphocyte-associated antigen 4 combination antibody. All 13 patients were treated with other anti-tumor drugs at the same time. There were 10 patients with a history of psoriasis and 3 patients with newly developed psoriasis. The median time from the use of ICIs to the onset or deterioration of psoriasis was 54 days. Ten patients were plaque psoriasis and 3 were drip psoriasis. Among the 13 patients, 5, 5, and 3 patients were classified as mild, moderate, and severe, respectively. ICIs treatment was suspended in 11 patients and not stopped in 2 patients. After treatment with glucocorticoids, the skin lesions of 13 patients were improved and ICIs were restarted in 3 patients.Conclusions:ICIs-related psoriasis usually occurs within 2 months after the use of ICIs. The clinical types are plaque-like and drop-like, mostly mild or moderate. The prognosis is good after discontinuing ICIs or giving glucocorticoids and other drugs. Some patients can restart ICIs treatment.

Objective:To analyze the clinical characteristics of immune-related psoriasis caused by immune checkpoint inhibitors (ICIs).Methods:The patients with newly developed or worsening psoriasis after ICIs treatment in Department of Oncology, the Affiliated Hospital of Qingdao University from November 2019 to October 2023 were enrolled in this study. The patients′ gender, age, tumor type and stage, usage and dosage of ICIs, drugs applied in combination, history of psoriasis, the time of new onset or deterioration, clinical manifestations, intervention measures and outcomes were collected, and descriptive statistical analysis was performed.Results:A total of 13 patients were enrolled in the study, including 10 males and 3 females, with a median age of 66 years. The primary diseases included lung cancer (in 7 patients), gastric cancer (in 5 patients), and cholangiocarcinoma (in 1 patient). The tumor stage was Ⅳ in 12 patients and Ⅲ in 1 patient. Ten patients were treated with programmed cell death 1 receptor (PD-1) inhibitors, 2 with programmed cell death ligand 1 (PD-L1) inhibitors, and one with a PD-1/cytotoxic T-lymphocyte-associated antigen 4 combination antibody. All 13 patients were treated with other anti-tumor drugs at the same time. There were 10 patients with a history of psoriasis and 3 patients with newly developed psoriasis. The median time from the use of ICIs to the onset or deterioration of psoriasis was 54 days. Ten patients were plaque psoriasis and 3 were drip psoriasis. Among the 13 patients, 5, 5, and 3 patients were classified as mild, moderate, and severe, respectively. ICIs treatment was suspended in 11 patients and not stopped in 2 patients. After treatment with glucocorticoids, the skin lesions of 13 patients were improved and ICIs were restarted in 3 patients.Conclusions:ICIs-related psoriasis usually occurs within 2 months after the use of ICIs. The clinical types are plaque-like and drop-like, mostly mild or moderate. The prognosis is good after discontinuing ICIs or giving glucocorticoids and other drugs. Some patients can restart ICIs treatment.

Objective:To explore the clinical manifestation, treatments, and outcomes of immune checkpoint inhibitor (ICI)-induced immune-mediated liver injury (IMLI).Methods:The patients with ICI- related IMLI and hospitalized in the Department of Oncology, the Affiliated Hospital of Qingdao University from January 2018 to November 2022 were collected. The basic information, tumor treatments, clinical manifestation, treatments and outcomes of the patients with IMLI were retrospectively analyzed.Results:A total of 29 patients were included in the study, including 17 males (58.6%) and 12 females (41.4%), with a median age of 65 years. The median treatment cycle from the use of ICI to the occurrence of liver injury was 3 cycles, and the median time was 78 days. In patients with IMLI, 48.3% (14/29) had no obvious symptoms and 51.7% (15/29) had symptoms such as decreased appetite, nausea, abdominal distension, fatigue, fever and jaundice; 44.8% (13/29) were accompanied by other immune-related adverse events. The clinical classification of IMLI was hepatocellular type in 18 patients (62.1%), cholestasis type in 4 patients (13.8%), and mixed type in 7 patients (24.1%). According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, severe liver injury (≥ grade 3) accounted for 86.2% (25/29), while according to the Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury (DILI guidelines) classification, severe liver injury (≥ grade 2) accounted for 34.5% (10/29). All 29 patients discontinued the treatment of ICIs after occurrence of IMLI, and 28 patients were treated with glucocorticoids, 7 of which were combined with mycophenolate mofetil and/or human immunoglobulin and artificial liver; 22 patients (75.9%) were improved. In the other 7 patients that did not recover, 4 discharged automatically, 2 died, and 1 could not be judged. ICI was rechallenged in 3 patients after liver function improvement, and IMLI did not recur. Conclusions:The IMLIs often occur 2 to 3 months after the start of ICI treatment, the most common clinical type is hepatocyte type, and the severity of clinical symptoms in patients vary from mild to severe. After discontinuing ICIs and receiving glucocorticoid treatments, most patients may have a good prognosis.

Objective:To explore the clinical manifestation, treatments, and outcomes of immune checkpoint inhibitor (ICI)-induced immune-mediated liver injury (IMLI).Methods:The patients with ICI- related IMLI and hospitalized in the Department of Oncology, the Affiliated Hospital of Qingdao University from January 2018 to November 2022 were collected. The basic information, tumor treatments, clinical manifestation, treatments and outcomes of the patients with IMLI were retrospectively analyzed.Results:A total of 29 patients were included in the study, including 17 males (58.6%) and 12 females (41.4%), with a median age of 65 years. The median treatment cycle from the use of ICI to the occurrence of liver injury was 3 cycles, and the median time was 78 days. In patients with IMLI, 48.3% (14/29) had no obvious symptoms and 51.7% (15/29) had symptoms such as decreased appetite, nausea, abdominal distension, fatigue, fever and jaundice; 44.8% (13/29) were accompanied by other immune-related adverse events. The clinical classification of IMLI was hepatocellular type in 18 patients (62.1%), cholestasis type in 4 patients (13.8%), and mixed type in 7 patients (24.1%). According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, severe liver injury (≥ grade 3) accounted for 86.2% (25/29), while according to the Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury (DILI guidelines) classification, severe liver injury (≥ grade 2) accounted for 34.5% (10/29). All 29 patients discontinued the treatment of ICIs after occurrence of IMLI, and 28 patients were treated with glucocorticoids, 7 of which were combined with mycophenolate mofetil and/or human immunoglobulin and artificial liver; 22 patients (75.9%) were improved. In the other 7 patients that did not recover, 4 discharged automatically, 2 died, and 1 could not be judged. ICI was rechallenged in 3 patients after liver function improvement, and IMLI did not recur. Conclusions:The IMLIs often occur 2 to 3 months after the start of ICI treatment, the most common clinical type is hepatocyte type, and the severity of clinical symptoms in patients vary from mild to severe. After discontinuing ICIs and receiving glucocorticoid treatments, most patients may have a good prognosis.

BACKGROUND: Occurrence at a younger age has been demonstrated to be associated with a distinct biology in non-small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next-generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma. METHODS: Eighty-nine surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinical pathologic characteristics of 95 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively. RESULTS: The frequencies of targetable genetic alterations in 184 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of anaplastic lymphoma kinase (ALK) and human epidermal growth factor receptor 2 (HER2) genetic alterations were associated with young age. However, a reverse trend was observed for kirsten rat sarcoma viral oncogene (KRAS), serine/threonine kinase 11 (STK11) and epidermal growth factor receptor (EGFR) exon 20 mutations, which were more frequently identified in the older group, aged more than 45 years. Furthermore, concurrent EGFR/tumor protein p53 (TP53) mutations were much more prevalent in the younger patients (81.6% vs 44.9%), which might have a poor response to treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI). CONCLUSIONS NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population.

Objective Next generation sequencing (NGS) was used for identifying the potential gene mutations in advanced gastric cancer(AGC) tissue in order to instruct the targeted drug use for AGC patients. Methods A total of 31 AGC patients from the Affiliated Hospital of Qingdao University between August 10, 2016 and April 23, 2017 were enrolled, and the tissues of gastric cancer were collected. 7 708 exons of 508 tumor related genes and 78 introns of 19 frequently rearranged genes were assessed for base substitutions, indels, copy number alterations, and gene fusions detection. The average median sequencing depth was 470×. Results Somatic mutations were detected in all the patients, of which 9.7 % (3/31) patients could select targeted drugs approved by National Comprehensive Cancer Network (NCCN) guideline according to the identified genetic alterations (human epidermal growth factor receptor 2 gene amplification / mutation). Other targetable genetic alterations were detected in 13 (41.9 %) AGC patients, including mTOR inhibitors, PARP inhibitors, FGFR inhibitors and other targeted drugs of mutations genes. Conclusion The detection of targeted genes based on NGS might help to identify available targeted drugs and to personalize targeted therapy for AGC patients.

Objective To explore antitumor effect of 131I-Trastuzumab on human epidermal growth factor receptor(HER) 2 overexpressing breast cancer cells and investigate its possible mechanism.Methods The expression levels of HER2 of three different breast cancer cell lines (BT474,MCF-7,HCC1937) were detected with immunofluorescence.Trastuzumab was labeled with 131I using the Iodogen method and 131I-Trastuzumab was isolated with ultrafiltration membrane,then the labeling efficiency,radiochemical purity and immunoreactivity were measured.The effects of 131I,Trastuzumab and 131I-Trastuzumab on viability of BT474 cells were evaluated with cell counting kit-8 (CCK-8) assay.The levels of total Akt and phosphorylated Akt (p-Akt) were detected with Western blot analysis.One-way analysis of variance (ANOVA),ANOVA for factorial design,Bonferroni correction and Pearson correlation analysis were used for data analysis.Results The expression level of HER2 in BT474 cells was much higher than those in HCC1937 and MCF-7 cells.The labeling efficiency,radiochemical purity and immunoreactivity of 131I-Trastuzumab were (89.71± 2.93)％,(91.80±1.43)％ and (58.84±3.35)％ respectively.131I (4.625 GBq/L),Trastuzumab(125.0 rmg/L) and 131I-Trastuzumab(4.625 GBq/L) exhibited a dose-dependent cytotoxicity against BT474 cells (r =-0.964,-0.912,-0.618;all P＜0.05).The cell viability of 131I-Trastuzumab treated gourp (34.73％ ±5.03％) was significantly lower than those of 131I and Trastuzumab treated groups (64.36％± 1.51％ and 58.09％±4.14％;t=10.373 and 8.180,both P＜0.05),and the cell viability of control group was (100.00±4.54)％.131I-Trastuzumab shown a positive multiplicative interaction between 131I and Trastuzumab (F=9.226,P＜0.05;CDI =0.929).Western blot results showed that there was no significant difference of total Akt expression among the control group,131I group,Trastuzumab group and 131I-Trastuzmab group (F=0.208,P＞0.05).P-Akt expression in both Trastuzumab group and 131I-Trastuzumab group were much lower than those of control group and 131I group (t=12.524,15.984,7.347,10.807;all P＜0.05),while there was no significant difference of p-Akt expression between Trastuzumab group and 131I-Trastuzumab group(t =3.460,P＞0.05).Conclusions 131I-Trastuzumab may kill HER2 overexpressing breast cancer cells more effectively than Trastuzumab alone.The underlying mechanism may be attributed to that 131I-Trastuzumab may enhance the radiosensitivity by the inhibitory effect on PI3K/Akt pathway and thus exert synergistic effects with 131I.