The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.

NK cells are an attractive target for cancer immunotherapy due to their potent antitumor activity. The main advantage of using NK cells as cytotoxic effectors over T cells is a reduced risk of graft versus host disease. At present, several variants of NK-cell-based therapies are undergoing clinical trials and show considerable effectiveness for hematological tumors. In these types of cancers, the immune cells themselves often undergo malignant transformation, which determines the features of the disease. In contrast, the current use of NK cells as therapeutic agents for the treatment of solid tumors is much less promising. Most studies are at the stage of preclinical investigation, but few progress to clinical trials. Low efficiency of NK cell migration and functional activity in the tumor environment are currently considered the major barriers to NK cell anti-tumor therapies. Various therapeutic combinations, genetic engineering methods, alternative sources for obtaining NK cells, and other techniques are aiming at the development of promising NK cell anticancer therapies, regardless of tumorigenesis. In this review, we compare the role of NK cells in the pathogenesis of hematological and solid tumors and discuss current prospects of NK-cell-based therapy for hematological and solid tumors.

HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agents.

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.

Review of Baduanjin and resistance exercise for the mental health of patients with hematologic malignancies.

Patients with hematological tumors experience physical and psychological stress, and negative psychological states. Baduanjin, an emerging psychological rehabilitation method combined with resistance exercise, has received widespread attention. This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects. Through a literature review and comprehensive analysis, the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated. The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors, which can alleviate anxiety, depression, and other adverse emotions, and improve quality of life. However, there is a lack of unified and standardized exercise intervention programs for practical application, and patient participation and compliance must be improved. Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors; however, it is still necessary to further standardize and improve the exercise program improving patient participation and compliance. Future studies should strengthen theoretical exploration and empirical research, providing more effective psychological rehabilitation strategies for patients with hematological tumors.

The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma.

INTRODUCTION: Cancer is the major cause of morbidity and mortality worldwide. Current treatments for both solid and hematological tumors are associated with severe adverse effects and drug resistance, necessitating the development of novel selective antineoplastic drugs. METHODS: The present study describes the antitumor activity of the imidazacridine derivative 5-acridin-9-ylmethylidene-2-thioxoimidazolidin-4-one (LPSF/AC05) in breast cancer, leuke-mia, and lymphoma cells. Cytotoxicity assays were performed in PBMC and in breast cancer, leukemia, and lymphoma cell lines using the MTT method. Changes in cell cycle progression and apoptosis were assessed using flow cytometry. Moreover, topoisomerase II inhibition as-says were performed. LPSF/AC05 exhibited cytotoxicity in six of the nine cell lines tested. RESULTS: The best results for leukemia and lymphoma were observed in the Toledo, Jurkat, and Raji cell lines (IC50 = 27.18, 31.04, and 33.36 M, respectively). For breast cancer, the best re-sults were observed in the triple-negative cell line MDA-MB-231 (IC50 = 27.54 µM). The compound showed excellent selectivity, with no toxicity to normal human cells (IC50 > 100M; selectivity index > 3). Cell death was primarily induced by apoptosis in all cell lines. Furthermore, LPSF/AC05 treatmentinduced cell cycle arrest at the G0/G1 phase in leuke-mia/lymphoma and at the G2/M phase in breast cancer. CONCLUSION: Finally, topoisomerase II was inhibited. These results indicate the potential ap-plication of LPSF/AC05 in cancer therapy.

The risk factors for coagulation disorder of chimeric antigen receptor-T cell therapy in patients with hematological tumors: A systematic review and meta-analysis.

BACKGROUND: Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. OBJECTIVE: We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms. METHODS: We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study. RESULTS: The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384-0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507-0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367-0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482-0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105-1 × 106 cell/kg, at a rate of 66.2% (95%[CI], 0.561-0.749). CONCLUSION: Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18-60, a dose of 1 × 105-1 × 106 cell/kg and BCMA-Car-T therapy are all considered high-risk factors.

Radiomics in Oncological PET Imaging: A Systematic Review-Part 2, Infradiaphragmatic Cancers, Blood Malignancies, Melanoma and Musculoskeletal Cancers.

The objective of this review was to summarize published radiomics studies dealing with infradiaphragmatic cancers, blood malignancies, melanoma, and musculoskeletal cancers, and assess their quality. PubMed database was searched from January 1990 to February 2022 for articles performing radiomics on PET imaging of at least 1 specified tumor type. Exclusion criteria includd: non-oncological studies; supradiaphragmatic tumors; reviews, comments, cases reports; phantom or animal studies; technical articles without a clinically oriented question; studies including <30 patients in the training cohort. The review database contained PMID, first author, year of publication, cancer type, number of patients, study design, independent validation cohort and objective. This database was completed twice by the same person; discrepant results were resolved by a third reading of the articles. A total of 162 studies met inclusion criteria; 61 (37.7%) studies included >100 patients, 13 (8.0%) were prospective and 61 (37.7%) used an independent validation set. The most represented cancers were esophagus, lymphoma, and cervical cancer (n = 24, n = 24 and n = 19 articles, respectively). Most studies focused on 18F-FDG, and prognostic and response to treatment objectives. Although radiomics and artificial intelligence are technically challenging, new contributions and guidelines help improving research quality over the years and pave the way toward personalized medicine.

Cost-effectiveness analysis of rhTPO and rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia in hematological tumors based on real-world data.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system. METHODS: We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed. RESULTS: A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO. CONCLUSIONS: In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.

The role of sterile chitosan-based dressing in reducing complications related to a peripherally inserted central catheter in patients with hematological tumors.

BACKGROUND: Intravenous chemotherapy is one of the most common treatments for hematological tumors, a major threat to human health and life. Due to its safety, comfort, and convenience, a peripherally inserted central catheter (PICC) is the preferred route of administration of intravenous chemotherapy. However, some PICC-related complications are drawing increasing attention. In this study, we investigated the use and role of sterile chitosan-based dressing in PICC-related complications in patients with hematological tumors. METHODS: We retrospectively analyzed the clinical data of 205 patients with hematological tumors who had a PICC placed. The patients were divided into two groups, the observation group (sterile chitosan-based dressing, n=105) and the control group (sterile gauze dressing; n=100). The incidences of bleeding, infection, poor healing, and phlebitis, as well as the risk of bleeding, infection, and poor healing at the puncture site within a week of PICC placement, were analyzed. RESULTS: The overall incidences of bleeding, infection, and poor healing were, respectively, 42.9%, 6.7%, and 6.7% in the observation group and 63.0%, 22.0%, and 34% in the control group (all P<0.05). The risk of local bleeding was significantly lower in the observation group than in the control group [odds ratio (OR) 0.366; 95% confidence interval (CI): 0.211-0.634; P<0.001]. The risk of local bleeding was significantly higher in the platelets <50×109/L group than in the platelets >100×109/L group (OR 3.068; 95% CI: 1.397-6.740; P=0.005), while no significant difference was observed in the risk of bleeding between the platelets 50×109-100×109/L group and the platelets >100×109/L group (OR 0.839; 95% CI: 0.404-1.742; P=0.638). The risk of infection (OR 0.214; 95% CI: 0.088-0.522; P<0.001) and the risk of poor healing (OR 0.139; 95% CI: 0.058-0.331; P<0.001) were significantly lower in the observation group than in the control group. CONCLUSIONS: For patients with hematological tumors, sterile chitosan-based dressing after PICC placement reduces the risk of bleeding and infection and promotes healing at the puncture site.

Characteristics of palliative home care for patients with hematological tumors compared to those of patients with solid tumors.

Home care medicine is a platform for providing supportive care for end-stage cancers. However, for undefined reasons, patients with hematological tumors (HTs) often fail to receive opportunities for home care. We, therefore, sought to delineate the clinical differences between solid tumors (STs) and HTs and to determine whether home care is effective for patients with HTs, as well as those with STs. We retrospectively analyzed the treatments, prognosis, and places of death of patients with STs (n = 99) and HTs (n = 20) who received palliative home care in our clinic and subsequently died between May 2016 and May 2018. Patients with HTs commonly required intravenous antibiotics, platelet transfusion, and red blood cell transfusion, while patients with STs tended to more frequently require the use of opioids. Importantly, there were no significant differences between the cohorts with respect to survival time and frequency of emergent visits to patients after their referral to us. Furthermore, most patients in both groups died at home. More than 50% of patients were not admitted to hospitals during our follow-up. Collectively, while therapeutic approaches sometimes differ, this study provides clinical evidence that palliative home care can be feasible even for patients with HTs.

Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma Management

The Protein kinase CK2 (formerly known as casein kinase 2) is a highly conserved serine/ threonine kinase overexpressed in various human carcinomas and its high expression often correlates with poor prognosis. CK2 protein is localized in the nucleus of many tumor cells and correlates with clinical features in many cases. Increased expression of CK2 in mice results in the development of various types of carcinomas (both solids and blood related tumors, such as (breast carcinoma, lymphoma, etc), which reveals its carcinogenic properties. CK2 plays essential roles in many key biological processes related to carcinoma, including cell apoptosis, DNA damage responses and cell cycle regulation. CK2 has become a potential anti-carcinoma target. Various CK2 inhibitors have been developed with anti-neoplastic properties against a variety of carcinomas. Some CK2 inhibitors have showed good results in in vitro and pre-clinical models, and have even entered in clinical trials. This article will review effects of CK2 and its inhibitors on common carcinomas in in vitro and pre-clinical studies.

Cateteres venosos totalmente implantáveis em pacientes com neoplasia hematológica e não hematológica / Totally implantable venous catheters in patients with hematological and non hematological neoplasias

OBJETIVO: Analisar se a presença de neoplasia hematológica acarreta maior risco de complicações para inserção de cateteres totalmente implantáveis e se há diferença de tempo cirúrgico quando o procedimento é realizado por punção ou dissecção venosa. MÉTODO: Foram avaliados 68 pacientes com neoplasia internados no Hospital Santa Rita de Porto Alegre entre fevereiro de 1998 e dezembro de 1999, os quais necessitavam de acesso venoso central para tratamento quimioterápico, sendo 48 do sexo feminino e com idade média de 55,6 anos. Desses, 31 apresentavam neoplasia hematológica. RESULTADOS: Complicações pós-operatórias ocorreram em 13 pacientes (19 por cento), sendo elas: obstrução do sistema (7 por cento), hematoma (6 por cento) e infecção (6 por cento), não havendo diferença quanto ao tipo de neoplasia (p = 0,56). Foram realizadas dissecção e punção venosa em 30 e 38 pacientes, respectivamente, sem diferença em relação ao tempo de implantação do cateter (p = 0,42). CONCLUSÃO: Neoplasias hematológicas não aumentaram o risco de complicações quando do uso de cateteres totalmente implantáveis no presente estudo, além disso, ambas as técnicas cirúrgicas - dissecção ou punção - são exeqüíveis, haja visto o tempo cirúrgico semelhante entre elas, desde que sejam respeitados o valor sérico mínimo de plaquetas (50.000/mL) e a técnica cirúrgica apropriada, com hemostasia rigorosa e curativo compressivo.

BACKGROUND: We analyse whether hematological tumors increase the risk of complications of totally implantable catheters and if there are differences regarding procedure time when it is perfomed through venous dissection or venous puncture. METHODS: We studied 68 patients with neoplasia in Hospital Santa Rita from Porto Alegre, between February 1998 and December 1999, who had required central venous access for chemotherapy. Forty-eight patients were female and the mean age was 55.6 years. Thirty-one patients had hematological tumors. RESULTS: Postoperative complications were observed in 13 patients (7 percent with device obstruction, 6 percent with hematoma and 6 percent with infection), but there was no difference regarding the pattern of the neoplasia (p = 0.56). Venous dissection and venous puncture were performed in 30 and 38 patients, respectively, with no difference concerning surgical time (p = 0.42). CONCLUSIONS: Hematological tumors did not increase the risk of complications of totally implantable catheters; furthermore, both surgical techniques (venous dissection or venous puncture) are acceptable choices, with similar surgical times, since one respects minimal platelet count of 50 000/mL and careful hemostasis techniques and compressive dressings.