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Hepatosplenic T cell lymphoma (HSTCL) is a particularly difficult-to-treat form of lymphoma, with many patients exhibiting primary resistance to chemotherapy. At present, no effective strategy for treating relapsed and refractory HSTCL has been established, with treatment being hampered by questions of how best to overcome chemoresistance to allow patients to attain more durable therapeutic benefits. While there have been marked advances in immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the primary approaches to curing HSTCL. Of patients who undergo immunochemotherapeutic treatment, many are resistant to conventional chemotherapeutic drugs yet remain sensitive to radiotherapy. We selected to employ a transplant pretreatment regimen consisting of total -body irradiation (TBI) and administered this regimen to two patients with HSTCL. Both patients achieved complete remission (CR) after transplantation, demonstrating extended periods without disease recurrence. We systematic reviewed previously published instances involving allo-HSCT in patients with HSTCL. We have found a total of 67 patients who have received allo-HSCT. In general, age

N6-methyladenosine (m6A) is the most prevalent internal modification found in both mRNA and lncRNA. It exerts reversible regulation over RNA function and affects RNA processing and metabolism in various diseases, especially tumors. The m6A binding protein, hnRNPA2B1, is extensively studied as a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It is frequently dysregulated and holds significant importance in multiple types of tumors. By recognizing m6A sites for variable splicing, maintaining RNA stability, and regulating translation and transport, hnRNPA2B1 plays a vital role in various aspects of tumor development, metabolism, and regulation of the immune microenvironment. In this review, we summarized the latest research on the functional roles and underlying molecular mechanisms of hnRNPA2B1. Moreover, we discussed its potential as a target for tumor therapy.

BackgroundRecently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis.MethodsBased on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients.ResultsWe proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines.ConclusionsEvaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment.

Background and purposeIt is crucial to evaluate the efficacy, recurrence, and metastasis of liver tumors after clinical treatment. This study aimed to investigate the value of Introvoxel Incoherent Motion (IVIM) imaging in the evaluation of rabbit VX2 liver tumors treated with Transcatheter Arterial Embolization (TAE) combined with apatinib.MethodsTwenty rabbit VX2 liver tumor models were established and randomly divided into either the experimental group (n=15) or the control group (n=5). The experimental group was treated with TAE combined with oral apatinib after successful tumor inoculation, while no treatment was administered following inoculation in the control group. IVIM sequence scan was performed in the experimental group before treatment, at 7 and 14 days after treatment. All rabbits were sacrificed after the last scan of the experimental group. Marginal tissues from the tumors of both groups were excised for immunohistochemical analysis to observe and compare the expression of microvessel density (MVD). The alterations of IVIM-related parameters of tumor tissues in the experimental group, including Apparent Diffusion Coefficient (ADC), True Diffusion Coefficient (D), Pseudodiffusion Coefficient (D*), and Perfusion Fraction (f) were compared at different periods, and the correlation between these parameters and MVD was analyzed.ResultsAfter treatment, ADC and D values significantly increased, whereas D* and f values both decreased, with statistically significant differences.(P0.05).ConclusionIVIM imaging can be employed to evaluate the efficacy of TAE combined with apatinib in rabbit VX2 liver tumors. Alterations in D and f values were closely related to the MVD of liver tumor tissues.

Simultaneous inhibition of more than one target is considered to be a novel strategy in cancer therapy. Owing to the importance of histone deacetylases (HDACs) and p53-murine double minute 2 (MDM2) interaction in tumor development and their synergistic effects, a series of MDM2/HDAC bifunctional small-molecule inhibitors were rationally designed and synthesized by incorporating an HDAC pharmacophore into spirooxindole skeletons. These compounds exhibited good inhibitory activities against both targets. In particular, compound 11b was demonstrated to be most potent for MDM2 and HDAC, reaching the enzyme inhibition of 68% and 79%, respectively. Compound 11b also showed efficient antiproliferative activity towards MCF-7 cells with better potency than the reference drug SAHA and Nutlin-3. Furthermore, western blot analysis revealed that compound 11b increased the expression of p53 and Ac-H4 in MCF-7 cells in a dose-dependent manner. Our results indicate that dual inhibition of HDAC and MDM2 may provide a novel and efficient strategy for the discovery of antitumor drug in the future.

Nowadays, breast cancer has become the most common cancer worldwide with a high mortality rate. Immune checkpoint blockade holds great promise in tumor‐targeted therapy, and CD47 blockade as one immune therapy is undergoing various preclinical studies and clinical trials to demonstrate its safety and efficacy in breast cancer. In this review, we summarized different therapeutic mechanisms targeting CD47 and its prognostic role and therapeutic value in breast cancer.

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

IntroductionBasal cell carcinoma (BCC) located on the genitalia is rare; data on the clinicopathologic features and survival outcomes are only available through case reports and small case series studies.PurposeThis study aimed to explore the epidemiology and identify the prognostic factors of genital BCCs.MethodsWe queried the 18 registries of the Surveillance, Epidemiology, and End Results database for patients with primary BCCs of the genital skin from 2000 through 2017. The primary endpoint was overall survival (OS) and disease specific survival (DSS). Kaplan-Meier survival analysis was conducted to assess the impact of clinicopathological variables on OS and DSS. Multivariate Cox proportional hazards model was performed to evaluate risk factors for OS.ResultsA total of 1,607 cases of genital BCCs were identified. The cohort was composed of 1,352 women (84.1%) and 255 men (15.9%). The median (P25, P75) age of the entire cohort was 73(63–82)years. White patients accounted for 87.2% of the cases. For women and men, the most common site of involvement was the labia majora (89.6%) and scrotum (74.5%), respectively. The majority of patients with genital BCC had localized disease (75.5%). Kaplan-Meier survival analysis showed that female genital BCCs experienced better DSS than men (209.1 months vs 194.8 months); for men, BCCs located on the scrotum had better DSS and OS than those on the penis (P < 0.05 for both endpoints). All patients with distant disease died of disease-specific death, and the average survival time was 8.2 months. Multivariate analysis revealed that age, primary site, and stage were independent determinants of OS for men, while tumor size, histologic subtype, and race were not. For women, factors associated with worse OS included increasing age, tumor size more than 2 cm, and distant disease; factors associated with a decreased risk included “other” and “unknown” races.ConclusionThe prognosis of genital BCCs is excellent, while the survival of distant disease is very poor. Despite similar clinicopathologic features and overall survival outcomes, men and women should be treated as two different entities when making survival predictions.

N6-methyladenosine (m6A) is the most prevalent internal modification found in both mRNA and lncRNA. It exerts reversible regulation over RNA function and affects RNA processing and metabolism in various diseases, especially tumors. The m6A binding protein, hnRNPA2B1, is extensively studied as a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It is frequently dysregulated and holds significant importance in multiple types of tumors. By recognizing m6A sites for variable splicing, maintaining RNA stability, and regulating translation and transport, hnRNPA2B1 plays a vital role in various aspects of tumor development, metabolism, and regulation of the immune microenvironment. In this review, we summarized the latest research on the functional roles and underlying molecular mechanisms of hnRNPA2B1. Moreover, we discussed its potential as a target for tumor therapy. [ABSTRACT FROM AUTHOR]