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Patient-derived tumour organoids (PDOs) have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and maintain the genomic, proteomic and morphological characteristics of parental tumours. Given these characteristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly. Here, we summarise recent advancements in PDOs from the perspective of cancer biology and clinical applications, focusing on the current challenges and opportunities of reconstructing and standardising more sophisticated PDO models. STATEMENT OF SIGNIFICANCE: Patient-derived tumour organoids (PDOs), three-dimensional (3D) self-assembled organotypic structures, have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and maintain the genomic, proteomic and morphological characteristics of parental tumours. Given these characteristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly.

To retrospectively evaluate the clinical efficacy and safety of percutaneous kyphoplasty (PKP) for the management of osteoblastic-related metastatic vertebral lesions.A total of 31 patients with 58 osteoblastic-related metastatic vertebral lesions underwent PKP were reviewed. The clinical efficacy was assessed based on parameters including visual analogue scale, Oswestry Disability Index, vertebral body height variation and quality of life. Major and minor complications were systematically evaluated to assess the safety of the procedure.Average follow-up period was 22.5 ± 11.1 months(range, 3 to 46 months). The procedure duration time ranged from 50 to 180 minutes (average 96.8 ± 36.9 minutes). Mean visual analogue scale scores decreased significantly from 6.1 ± 1.8 pre-operatively to 2.7 ± 1.5 at 3 days after PKP (p0.001), and remained largely immutable at 1 month (2.0 ± 0.7; 31 patients; p0.001), 3 months (2.4 ± 1.2; 30 patients; p0.001) and 1 year (3.0 ± 1.0; 27 patients; p0.001). Oswestry Disability Index scores and vertebral body height variation also changed after the procedure, with significant differences between pre-operative scores and at each follow-up examination (p0.001). Mean quality of life scores were 90.8 ± 12.9 pre-operatively and improved to 99.5 ± 12.1(27 patients, p0.001) at 1 year after PKP. The only minor encountered complication was bone cement leakage, which was seen in 6.5%(2 of 31) of patients. None of the patients experienced major complications.PKP is a safe and effective treatment strategy for osteoblastic-related metastatic vertebral lesions from a variety of tumor etiologies.

To compare the clinical and radiographic results of bipedicular and unipedicular approaches(UPK and BPK) in the management of metastatic vertebral lesions MATERIALS AND METHODS: Eighty-two patients with 159 metastatic vertebral lesions who underwent UPK(25 cases, 69 lesions) or BPK(57 cases, 90 lesions) were retrospectively evaluated. Clinical results were assessed mainly depending on the Visual Analogue Scale(VAS) score, Oswestry Disability Index(ODI) and Quality of Life(QoL). Radiographic outcomes were evaluated primarily on the basis of bone cement distribution and changes in vertebral body height(VBH). Major and minor complications were systematically evaluated and compared to assess the safety of the 2 procedures.No statistically significant differences were observed in age, sex, types of lesions, location of lesions, posterior vertebral body and/or pedicle involvement, percentage of vertebra invasion between the groups(p=0.17-0.83). The radiographic parameter VBH was similarly improved in both groups(p=0.26-0.93). There was a significant improvement in the clinical parameters VAS score, ODI, and QoL at each follow-up examination compared with the preoperative results(p0.001). Significant improvement was observed in the VBH at each follow-up point(p0.05) compared to pre-procedure. UPK was superior to BPK in terms of the operative duration(p0.001), cement volume(p=0.004), and surgical complications(p=0.04).Both UPK and BPK resulted in similar clinical and radiographic outcomes in patients with metastatic vertebral lesions. The UPK had advantages including a shorter operation and lower cement volume than the BPK, which may have played an important role in reducing the incidence of complications. UPK can replace BPK in the treatment of metastatic vertebral lesions.

Cyclin-dependent kinase 12 (CDK12), a transcription-related cyclin dependent kinase (CDK), plays a momentous part in multitudinous biological functions, such as replication, transcription initiation to elongation and termination, precursor mRNA (pre-mRNA) splicing, intron polyadenylation (IPA), and translation. CDK12 can act as a tumour suppressor or oncogene in disparate cellular environments, and its dysregulation likely provokes tumorigenesis. A comprehensive understanding of CDK12 will tremendously facilitate the exploitation of novel tactics for the treatment and precaution of cancer. Currently, CDK12 inhibitors are nonspecific and nonselective, which profoundly hinders the pharmacological target validation and drug exploitation process. Herein, we summarize the newly comprehension of the biological functions of CDK12 with a focus on recently emerged advancements of CDK12-associated therapeutic approaches in cancers.

We aimed to investigate the clinical outcomes of percutaneous kyphoplasty (PKP) for spinal metastases in older adult patients with comorbidities.Ninety-two older adults (age ≥ 60 years) with spinal metastases who underwent 148 PKP procedures were retrospectively analyzed. Tokuhashi scores, Tomita scores, age-adjusted Charlson Comorbidity Index (aCCI) scores, and American Society of Anesthesiologists (ASA) scores were evaluated before the procedure. The visual analog scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH), and quality of life (QoL) were used to assess the efficacy of the procedure. Clinical safety was evaluated based on periprocedural complications.Tokuhashi scores and Tomita scores were 7.3 ± 4.0 and 5.8 ± 2.1, respectively. Excluding cancer-related factors, twelve patients (13.0%) had aCCI scores ≥4. Forty-three patients (46.7%) had ASA status ≥ III. Compared to preoperative status, average VAS scores, ODI scores, VBH variation, and QoL scores significantly improved at each follow-up examination point after PKP (p 0.001). No major complications occurred, nor was there decompensation of comorbidities in the perioperative period. Seventeen segments (11.5%) of twelve patients (13.0%) suffered bone cement leakage. Among them, one patient suffered intercostal neuralgia cured by steroid injection, and the other patient suffered hyperesthesia, which disappeared after taking gabapentin (0.3 g, bid) for five weeks. Another minor complication of local hematoma occurred in one patient, which spontaneously resolved without surgical intervention.PKP serves as a safe approach to provide significant pain relief, vertebral body height restoration, and QoL improvements for spinal metastases in older adults, independent of underlying disease.

The dissimilarity is a major problem in clinical therapy of skin cutaneous melanoma (SKCM). Objective and reproducible classification systems may help decode SKCM heterogeneity. ConsensusClusterPlus was used to establish a stable immune molecular classification based on ferroptosis-related genes that had been acquired from FerrDb. Moreover, the prognosis, somatic mutations, immune microenvironment characteristics, functional enrichment, and clinical responsiveness to the immune checkpoint blockade of different subtypes in two independent melanin datasets were compared. Kaplan-Meier curves, univariate, multivariate, least absolute contraction, and selection operator (LASSO) Cox regression analysis were used to develop a molecular model for predicting survival, which was verified by a nomogram on the basis of independent prognostic indicators. Two molecular subtypes (C1 and C2) for SKCM were first identified according to ferroptosis-related genes; C1 showed a poor prognosis, with lower infiltration degree of immune cells and TIED score and higher homologous recombination defects, fraction altered, the number of segments, and copy number amplification and deletion. These characteristics of C2 were the opposite of C1. A ferroptosis-related prognosis risk score (FPRS) model was constructed using 6 of 463 genes with differential expression between C1 and C2. This model splits patients into low- and high-risk cohorts. There were significant differences in the infiltration and proportion of immune cells, immune checkpoint gene expression, responsiveness to immune checkpoint therapy, and sensitivity to chemotherapeutic medications between low- and high-risk cohorts. This model was an independent prognostic marker for SKCM and has a high AUC. In summary, we have identified two subtypes of SKCM with different molecular and immune characteristics on the basis of ferroptosis-related genes and further developed and verified an FPRS model, which might independently serve as a prognostic marker for SKCM.