Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Hepatocellular carcinoma (HCC) ranks as the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Current serum biomarkers for HCC surveillance and early diagnosis, particularly alpha-fetoprotein (AFP) the most commonly used marker, lack satisfactory sensitivity and specificity, highlighting an urgent need for more effective markers with higher accuracy for early HCC detection. The downregulation of melanoma-associated antigen D1 (MAGE-D1) transcription plays a crucial role in apoptosis and inhibits cancer cell proliferation when expressed ectopically. ⋯ The performance of serum MAGED-1 expression in discrimination between HCC and chronic liver condition revealed an area under the curve (AUC) of 0.939 using the cutoff (0.752) yielded a sensitivity of 90%, specificity of 85%, and an accuracy of 91%. Evaluation of the diagnostic significance of MAGED-1 demonstrated an AUC value of 0.726, with a sensitivity of 63.6% and a specificity of 73.5%. In conclusion, MAGED-1 might be a specific and sensitive biomarker for HCC, potentially improving the malignancy diagnosis and prognosis.
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Immunotherapy with checkpoint inhibitors has improved the outcomes of patients with metastatic lung cancer in recent years. Despite improved prognosis, not all patients respond to treatment. Therapeutic interventions to build on the success of immune checkpoint inhibitors are needed. ⋯ Palliative radiation therapy administered in proximity with immune checkpoint inhibitors immunotherapy had no effect on the OS of metastatic lung cancer patients. However, patients receiving palliative radiotherapy with fractions above 700 cGy showed better OS. Further studies are needed to optimize a combination strategy.
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Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset colorectal cancer (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. ⋯ A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p < 0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.
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In many COVID-19 survivors, symptoms continue for a long time. This study aims to examine the relationship between the long-term effects of COVID-19, levels of anxiety and depression, and suicidal ideation with sociodemographic factors and symptoms. A cross-sectional study was conducted on patients who came for control at least 3 months after having COVID-19 disease, in the stable period, and still have symptoms after COVID-19. ⋯ Both BAS and BDS scores were significantly higher in people with suicidality compared to others, and long-term symptoms were found to be statistically associated with this situation. Depression and anxiety are common in cases of long COVID. It is important for healthcare professionals to be aware of these potential mental health consequences, especially suicidality, and to provide appropriate support and interventions for individuals with long COVID.
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NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay. ⋯ Remarkably, we found that dexamethasone enhanced the cytotoxicity of IL21-NKG2D CAR-T cells on MM cells. Furthermore, IL21-NKG2D CAR-T cells also displayed significant anti-myeloma activity in vivo. In conclusion, IL21-NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro and in vivo, and a system to apply IL21-NKG2D CAR-T cells and low dosage of dexamethasone for the future study of the targeted therapy for MM has been established.