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Simple Summary: Ultrasound (US) imaging is a safe, convenient imaging method for identifying malignant lymph nodes. Shear wave elastography (SWE), as a type of US elastography offers the mechanical information of tissue by sensing shear wave propagation in lymph nodes. Malignant lymph nodes can show increased stiffness at the lesion margin and adjacent tissue on the SWE image. However, the diagnostic accuracies of various SWE parameters that quantify tissue stiffness, such as maximum stiffness, mean stiffness, minimum stiffness, and standard deviation, are yet to be demonstrated. We included sixteen eligible studies to evaluate the pooled diagnostic accuracy of different SWE parameters. SWE has demonstrated promise as an imaging modality in diagnosing and differentiating malignancy from benign lymph nodes. Its incorporation into standard US allows for a better evaluation of the target region or lymph node and might reduce the need for invasive procedures or exposure to ionising radiation without compromising on diagnostic accuracy. Shear wave elastography (SWE) has shown promise in distinguishing lymph node malignancies. However, the diagnostic accuracies of various SWE parameters that quantify tissue stiffness are yet to be demonstrated. To evaluate the pooled diagnostic accuracy of different SWE parameters for differentiating lymph node malignancies, we conducted a systematic screening of four databases using the PRISMA guidelines. Lymph node biopsy was adopted as the reference standard. Emax (maximum stiffness), Emean (mean stiffness), Emin (minimum stiffness), and Esd (standard deviation) SWE parameters were subjected to separate meta-analyses. A sub-group analysis comparing the use of Emax in cervical (including thyroid) and axillary lymph node malignancies was also conducted. Sixteen studies were included in this meta-analysis. Emax and Esd demonstrated the highest pooled sensitivity (0.78 (95% CI: 0.69–0.87); 0.78 (95% CI: 0.68–0.87)), while Emean demonstrated the highest pooled specificity (0.93 (95% CI: 0.88–0.98)). From the sub-group analysis, the diagnostic performance did not differ significantly in cervical and axillary LN malignancies. In conclusion, SWE is a promising adjunct imaging technique to conventional ultrasonography in the diagnosis of lymph node malignancy. SWE parameters of Emax and Esd have been identified as better choices of parameters for screening clinical purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiparametric magnetic-resonance imaging (mpMRI) is a routinely used imaging modality for diagnosing prostate cancer but misses 10–20% of prostate tumours. Recently, prostate-specific membrane antigen positron-emission tomography (PSMA PET) has been proposed as an alternative to mpMRI for diagnosis. Our systematic review and meta-analysis aimed to compare the diagnostic performance between mpMRI and PSMA PET modalities prior to biopsy. Ten articles directly comparing the performance of both modalities in the same patient cohort were investigated. PSMA PET/CT was superior in diagnosing patients with prostate cancer over mpMRI, but not in defining the location of the cancer. Early evidence suggests that the addition of PSMA PET within the diagnostic pathway may enhance the detection of clinically significant prostate cancer. Multiparametric magnetic-resonance imaging (mpMRI) has proven utility in diagnosing primary prostate cancer. However, the diagnostic potential of prostate-specific membrane antigen positron-emission tomography (PSMA PET) has yet to be established. This study aims to systematically review the current literature comparing the diagnostic performance of mpMRI and PSMA PET imaging to diagnose primary prostate cancer. A systematic literature search was performed up to December 2021. Quality analyses were conducted using the QUADAS-2 tool. The reference standard was whole-mount prostatectomy or prostate biopsy. Statistical analysis involved the pooling of the reported diagnostic performances of each modality, and differences in per-patient and per-lesion analysis were compared using a Fisher's exact test. Ten articles were included in the meta-analysis. At a per-patient level, the pooled values of sensitivity, specificity, and area under the curve (AUC) for mpMRI and PSMA PET/CT were 0.87 (95% CI: 0.83–0.91) vs. 0.93 (95% CI: 0.90–0.96, p < 0.01); 0.47 (95% CI: 0.23–0.71) vs. 0.54 (95% CI: 0.23–0.84, p > 0.05); and 0.84 vs. 0.91, respectively. At a per-lesion level, the pooled sensitivity, specificity, and AUC value for mpMRI and PSMA PET/CT were lower, at 0.63 (95% CI: 0.52–0.74) vs. 0.79 (95% CI: 0.62–0.92, p < 0.001); 0.88 (95% CI: 0.81–0.95) vs. 0.71 (95% CI: 0.47–0.90, p < 0.05); and 0.83 vs. 0.84, respectively. High heterogeneity was observed between studies. PSMA PET/CT may better confirm the presence of prostate cancer than mpMRI. However, both modalities appear comparable in determining the localisation of the lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Preclinical investigations have identified promising anti-tumor activity of a ketogenic diet in glioblastoma. Although a majority of the work has focused on how this diet directly influences tumor growth, our understanding of its impact on the tumor microenvironment remains limited. In this study, although the anti-tumor activity of a ketogenic diet in glioblastoma was validated, we uncovered a paradoxical increase in a "pro-tumoral" immune response, skewing tumor-associated macrophages towards an "M2-like" phenotype. We hypothesized this would limit the anti-tumor activity of a ketogenic diet, which was tested by combining this diet with a CSF-1 inhibitor. The combination of a ketogenic diet with CSF-1 inhibition normalized tumor-associated macrophages and led to a profound improvement in survival in mice. This provides rationale to test this novel combinatorial strategy in glioblastoma and highlights the importance of understanding how a given therapy influences both the tumor and its associated immune microenvironment. Glioblastoma (GBM) represents an aggressive and immune-resistant cancer. Preclinical investigations have identified anti-tumor activity of a ketogenic diet (KD) potentially being used to target GBM's glycolytic phenotype. Since immune cells in the microenvironment have a similar reliance upon nutrients to perform their individual functions, we sought to determine if KD influenced the immune landscape of GBM. Consistent with previous publications, KD improved survival in GBM in an immune-competent murine model. Immunophenotyping of tumors identified KD-influenced macrophage polarization, with a paradoxical 50% increase in immune-suppressive M2-like-macrophages and a decrease in pro-inflammatory M1-like-macrophages. We recapitulated KD in vitro using a modified cell culture based on metabolomic profiling of serum in KD-fed mice, mechanistically linking the observed changes in macrophage polarization to PPARγ-activation. We hypothesized that parallel increases in M2-macrophage polarization tempered the therapeutic benefit of KD in GBM. To test this, we performed investigations combining KD with the CSF-1R inhibitor (BLZ945), which influences macrophage polarization. The combination demonstrated a striking improvement in survival and correlative studies confirmed BLZ945 normalized KD-induced changes in macrophage polarization. Overall, KD demonstrates antitumor activity in GBM; however, its efficacy is attenuated by promoting an immunosuppressive phenotype in macrophages. Combinatorial strategies designed to modulate macrophage polarization represent a rational approach to improve the anti-tumor activity of KD in GBM. [ABSTRACT FROM AUTHOR]

Simple Summary: Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis. Therefore, early identification of high-risk extramedullary relapse patients has important clinical significance. However, due to the lack of a large prospective clinical study, clinical characteristic evidence for the early identification of patients with extramedullary relapse is still lacking. Our study analyzed the high-risk factors for extramedullary relapse in NDMM patients for the first time, hoping to identify high-risk extramedullary relapse patients as early as possible to take early measures to prevent extramedullary relapse and improve the overall prognosis of NDMM patients. Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis, but our understanding of extramedullary relapse is still limited. The incidence, clinical characteristics, impact on the prognosis of extramedullary relapse, and the risk factors for extramedullary relapse in NDMM patients were analyzed. Among the 471 NDMM patients, a total of 267 patients had disease relapse during follow-up, including 64 (24.0%) patients with extramedullary relapse. Extramedullary relapse was more common in patients with younger age, IgD subtype, elevated LDH, extensive osteolytic lesions, extramedullary involvement, and spleen enlargement at the time of MM diagnosis. Survival analysis showed that extramedullary relapse patients had significantly worse median OS than patients with relapse but without extramedullary involvement (30.8 months vs. 53.6 months, p = 0.012). Multivariate analysis confirmed that elevated LDH (OR = 2.09, p = 0.023), >2 osteolytic lesions (OR = 3.70, p < 0.001), extramedullary involvement (OR = 3.48, p < 0.001) and spleen enlargement (OR = 2.27, p = 0.011) at the time of MM diagnosis were independent risk factors for extramedullary relapse in NDMM patients. Each of the above four factors was assigned a value of 1 to form the extramedullary relapse prediction score, and the 3-year extramedullary relapse rates of patients in the 0–2 and 3–4 score groups were 9.0 % and 76.7 %, respectively. This study suggested that extramedullary relapse was associated with poor clinical characteristics and poor prognosis in NDMM patients. The extramedullary relapse prediction score model composed of LDH, osteolytic lesions, extramedullary involvement and spleen enlargement has a better ability to predict extramedullary relapse than the existing ISS and R-ISS stages. [ABSTRACT FROM AUTHOR]

Background: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras, the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated that β-catenin’s differential usage of the Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous coactivator p300 increases self-renewal and suppresses differentiation in other types of cancer. Aim/methods: To investigate Wnt-mediated carcinogenesis in PDAC, we have used the specific small molecule CBP/β-catenin antagonist, ICG-001, which our lab identified and has extensively characterized, to examine its effects in human pancreatic cancer cells and in both an orthotopic mouse model and a human patient-derived xenograft (PDX) model of PDAC. Results/conclusion: We report for the first time that K-Ras activation increases the CBP/β-catenin interaction in pancreatic cancer; and that ICG-001 specific antagonism of the CBP/β-catenin interaction sensitizes pancreatic cancer cells and tumors to gemcitabine treatment. These effects were associated with increases in the expression of let-7a microRNA; suppression of K-Ras and survivin; and the elimination of drug-resistant cancer stem/tumor-initiating cells. [ABSTRACT FROM AUTHOR]