Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[The anatomic zone localization based on biparametric MRI for the prediction of the risk degree of prostate cancer].

Objective: To investigate the anatomic zone localization based on biparametric magnetic resonance imaging (bpMRI) for the prediction of the risk degree in patients with prostate cancer. Methods: A total of 92 patients with prostate cancer confirmed by radical surgery in First Affiliated Hospital, Air Force Medical University, from January 2017 to December 2021 were collected. All patients underwent bpMRI (non-enhanced scan and DWI). According to ISUP grade, those patients were divided into low-risk group [≤grade 2, n=26, aged 71 (64.0, 5.2) years] and high-risk group[≥grade 3, n=66, aged 70.5 (63.0, 74.0) years]. The interobserver consistency test for ADC values was evaluated using the intraclass correlation coefficients (ICC). The differences in total prostate specific antigen (tPSA) between the two groups were compared and the χ2 test was used to compare the differences in the risk of prostate cancer in the transitional and peripheral zone. Independent correlation factors for prostate cancer risk were analyzed by logistic regression using high and low risk of prostate cancer as dependent variables, including factors such as anatomical zone, tPSA, apparent diffusion coefficient mean (ADCmean), apparent diffusion coefficient minimum (ADCmin) and age. Receiver operating characteristic (ROC) curves were plotted to assess the efficacy of the combined models of anatomical zone, tPSA, and anatomical partitioning+tPSA for diagnosing prostate cancer risk. Results: The ICC values of the ADCmean and ADCmin between the observers were 0.906 and 0.885, respectively, with good agreement. The tPSA in the low-risk group was lower than that in the high-risk group [19.64 (10.29, 35.18) ng/ml vs 72.42 (24.79, 187.98) ng/ml; P<0.001]; the risk of prostate cancer in the peripheral zone was higher than that in the transitional zone, and the difference was statistically significant (P<0.01). Multifactorial regression showed that anatomical zones (OR=0.120, 95%CI:0.029-0.501, P=0.004) and tPSA (OR=1.059, 95%CI:1.022-1.099, P=0.002) were risk factors for prostate cancer risk. The diagnostic efficacy of the combined model (AUC=0.895, 95%CI: 0.831-0.958) was better than the predictive efficacy of the single model for both anatomical partitioning (AUC=0.717, 95%CI:0.597-0.837) and tPSA (AUC=0.801, 95%CI: 0.714-0.887) (Z=3.91, 2.47; all P<0.05). Conclusions: The malignant degree of prostate cancer in peripheral zone was higher than that in transitional zone. Combination of anatomic zone located by bpMRI and tPSA can be used to predict the risk of prostate cancer before surgery, expected to provide support for patients to develop personalized treatment strategies.

MiR-126 inhibits cell migration and invasion by targeting ADAM9 in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC), the most frequent head and neck cancer, has a high potential for metastasis. MiR-126 plays an important role in the tumorigenesis of many tumors; however, there were little studies in OSCC. The purpose of our study was to explore how miR-126 and ADAM9 worked on migration and invasion in OSCC. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was applied to detect the mRNA level of miR-126 and ADAM9. The transwell assay was utilized to calculate the migratory and invasive capacities in the OSCC cells. The luciferase report assay was utilized to verify that ADAM9 was a direct target of miR-126. RESULTS: MicroR-126 was downregulated in OSCC tissues and cell lines SCC25 and HSC3. ADAM9 was predicted to be a direct target of miR-126 and was upregulated in the OSCC cells. In addition, miR-126 suppressed the migratory and invasive ability via mediating the expression of ADAM9 by directly targeting its mRNA 3'-noncoding region (UTR), whose partial functions was reversed by ADAM9. CONCLUSIONS: MiR-126 inhibited the migratory and invasive capacities of OSCC by directly targeting the 3'-UTR of ADAM9 mRNA. It is suggested that miR-126/ADAM9 axis may play an essential role in inhibiting the abilities of migration and invasion in oral squamous cell carcinoma cells.

MiR-1290 targets CCNG2 to promote the metastasis of oral squamous cell carcinoma.

OBJECTIVE: MicroRNAs (miRNAs) have been demonstrated to be involved in the pathogenesis of various human cancers, including oral squamous cell carcinoma (OSCC). Here, we designed this study to explore the potential effect of miR-1290 on tumorigenesis of OSCC. PATIENTS AND METHODS: The expressions of miR-1290 and cyclin G2 (CCNG2) in OSCC were observed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Dual-Luciferase Reporter Assay was performed to confirm the relationship between miR-1290 and CCNG2. The functions of miR-1290 and CCNG2 were analyzed using transwell assay. The Western blot analysis was used to detect epithelial-mesenchymal transition (EMT). RESULTS: Upregulation of miR-1290 and downregulation of CCNG2 were identified in OSCC. And upregulation of miR-1290 was associated with clinicopathological characteristics and poor prognosis in OSCC patients. Moreover, the downregulation of miR-1290 inhibited cell metastasis and EMT in OSCC cells. Furthermore, CCNG2 was a direct target of miR-1290. Its expression was inversely regulated by miR-1290 in OSCC cells. At the same time, the suppressive effect of CCNG2 was observed in OSCC. Furthermore, overexpression of CCNG2 weakened the promoted effect of miR-1290 on cell metastasis in OSCC. CONCLUSIONS: MiR-1290 promoted cell metastasis and EMT, inhibiting CCNG2 expression in OSCC.

Mir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma.

OBJECTIVE: MicroRNAs have caught more attention for their role in tumor progression. Retinoblastoma (RB) is one of these ordinary malignant tumors. This study aims to identify whether mir-138-5p can regulate the development of RB, and find out its potential mechanism. MATERIALS AND METHODS: Mir-138-5p expression in RB cells was monitored by RT-qPCR. Besides, the role of mir-138-5p in RB development was explored through function experiments in vitro. The potential mechanism was further explored by RT-qPCR, luciferase assay, and Western blot assay. RESULTS: In our investigation, mir-138-5p was lower-expressed in RB cells than that in retinal pigment epithelial cells. Moreover, overexpression of mir-138-5p repressed cell viability, migration and invasion, and induced apoptosis of RB cells, while downregulated mir-138-5p increased cell viability, migration and invasion, and reduced apoptosis of RB cells. Furthermore, pyruvate dehydrogenase kinase 1 (PDK1) could be downregulated via overexpression of mir-138-5p, while PDK1 was upregulated via knockdown of mir-138-5p. CONCLUSIONS: Our results suggested that mir-138-5p could repress the development of RB via suppressing PDK1, which may offer a new vision for interpreting the mechanism of RB tumorigenesis.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report.

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

An hepatitis B virus surface antigen specific single chain of variable fragment derived from a natural immune antigen binding fragment phage display library is specifically internalized by HepG2.2.15 cells.

Hepatitis B virus surface antigen (HBsAg), a specific antigen on the membrane of hepatitis B virus (HBV)-infected cells, provides a perfect target for therapeutic drugs. In order to mediate successful targeted delivery of these therapies, it is essential to have antibodies that recognize HBsAg with high specificity and affinity. In this report, we constructed a natural immune antigen binding fragments (Fab) antibody phage display library against HBsAg and after three rounds of panning, five Fab fragments with significant HBsAg binding ability were selected and analysed. DNA sequencing revealed that all the light chains had the same sequence, while all the Fd genes exhibited different sequences. For further application, all of the Fab antibodies were reconstructed into single chain antibodies (scFvs) and expressed in Escherichia coli BL21 cells. Indirect enzyme-linked immunosorbent assay analysis demonstrated that all five scFvs maintained a high affinity for HBsAg and could bind HBsAg on the membrane of HBV-infected cells. Indirect fluorescent staining analysis revealed that one of the scFvs (scFv15) could be internalized into HBsAg-positive HepG2.2.15 cells through clathrin-mediated endocytosis pathway. The internalizing scFv15 antibody would have great potential for the targeted delivery of therapeutics to HBV-infected cells.