Objective: The present study aimed to systematically explore the potential targets and molecular mechanisms of matrine in the treatment of DLBCL.

Methods: Potential matrine targets were collected from multiple platforms. Microarray data and clinical characteristics of DLBCL were downloaded from publicly available database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to identify the hub genes of DLBCL using R software. Then, the shared target genes between matrine and DLBCL were identified as the potential targets of matrine against DLBCL. The least absolute shrinkage and selection operator (LASSO) algorithm was used to determine the final core target genes, which were further verified by molecular docking simulation and receiver operating characteristic (ROC) curve analysis. Functional analysis was also performed to elucidate the potential mechanisms.

Results: A total of 222 matrine target genes and 1269 DLBCL hub genes were obtained through multiple databases and machine learning algorithms. From the nine shared target genes of matrine and DLBCL, five final core target genes, including CTSL, NR1H2, PDPK1, MDM2, and JAK3, were identified. Molecular docking showed that the binding of matrine to the core genes was stable. ROC curves also suggested close associations between the core genes and DLBCL. Additionally, functional analysis showed that the therapeutic effect of matrine against DLBCL may be related to the PI3K-Akt signaling pathway.

Conclusion: Matrine may target five genes and the PI3K-Akt signaling pathway in DLBCL treatment.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Background: Lymphoma and leukemia, both malignant hematological cancers, are primarily different diseases, with a majority of cases originating independently. The co-occurrence of lymphoma and leukemia at the time of the first diagnosis is extremely rare, and few relevant reports exist in the medical literature. We describe a case of a patient with non-Hodgkin's lymphoma and acute myeloid leukemia, a very rare occurrence.

Case Report: A 57-year-old man complained of fatigue and neck tumors. A physical examination revealed several enlarged superficial lymph nodes throughout the body. On admission, routine blood tests revealed anemia, thrombocytopenia, and normal counts of white blood cells. Cytology of two cervical lymph nodes indicated non- Hodgkin's lymphoma, ¹⁸F-PET/CT: multiple enlarged lymph nodes with hypermetabolism, diffuse hypermetabolism of the bone marrow, suggesting lymphoma infiltration in the bone marrow, and a bone marrow biopsy revealed acute myeloid leukemia. Ultimately, the patient was diagnosed with non-Hodgkin’s lymphoma and acute myeloid leukemia.

Conclusion: Primary bilineage hematological malignancies are rare, and the mechanism underlying their incidence is unknown. Infiltration of the bone marrow by lymphoma or leukemia can result in diffuse hypermetabolism, mostly diagnosed via bone marrow biopsy.

Objective: The present study investigated the effect of NU 9056 in ENKTL cells and explored the possible molecular mechanism for its antitumour effect.

Methods: The role of NU 9056 in ENKTL cells was investigated through the Cell Counting Kit-8 assay, flow cytometry, Western blot, and real-time quantitative polymerase chain reaction assay.

Results: NU 9056 inhibited ENKTL cell proliferation and induced G2/M phase arrest. NU 9056 also induced apoptosis by upregulating DR4, DR5, and caspase 8 expressions. Additionally, NU 9056 increased the expression of Bax, Bid, and cytochrome C and decreased the expression of Bcl-2, Mcl-1, and XIAP. Furthermore, NU 9056 activated endoplasmic reticulum (ER) stress and inhibited the JAK2/STAT3 signalling pathway. The p38 mitogen-activated protein kinase (MAPK) signalling pathway was also activated by NU 9056, and the ERK signalling pathway was suppressed in natural killer/T cell lymphoma cells.

Conclusion: NU 9056 inhibited cell proliferation, arrested cell cycle in the G2/M phase, and induced apoptosis through the stimulation of ER stress, thus inhibiting the JAK2/STAT3 signalling pathway and regulating MAPK pathways in ENKTL cells.

Aim: To assess the severity of the adverse reactions of PD-1 and PD-L1 inhibitors in treating patients with positive PD-1 or PD-L1; non-small cell lung cancer patients (NSCLCs), small cell lung cancer (SCLC), nodular sclerosis Hodgkin lymphoma, classic Hodgkin's lymphoma, gastric cancer, renal cell carcinoma, caecal carcinoma, buccal mucosa carcinoma, nasopharyngeal carcinoma, laryngopharynx cancer, bladder cancer, cervical cancer, and melanoma.

Materials and Methods: The study data was collected and analyzed randomly from the period of January 2019 to November 2020 from the Mordovian oncological dispensary. The data are collected from the electronic archive of the hospital. Then, we followed up with the patients for the same period, and we recorded the presented adverse reactions. The patients received anti-tumor drug; PD-L1/PD-L inhibitors (Atezolizumab; 1200mg, Pembrolizumab; 200mg, and Nivolumab; 240mg or 3 mg/kg) every 21 or 14 days they got IV infusion of PD-1 and/or PD-L1 inhibitors. After the progression and metastasis of the tumor, the patients received a combination of chemotherapy prior to the immunotherapy.

Results: The analyzed data have shown 7.14% of the studied patients (n=28) have developed adverse reactions that ranged from mild to moderate severity (anemia and biochemical tests deviation).

Conclusion: These clinical findings supported the moderate risk of developing life-threatening adverse reactions after administration of immune checkpoint inhibitors (Nivolumab, Pembrolizumab, Atezolizumab) to patients with advanced-stage tumors. The patients who were treated with PD-1 inhibitors developed less severe adverse reactions than patients who were treated with PD-L1 inhibitors. The adverse reaction severity depends on the period of administration and the type of the treated tumor, which consequently determines the dose of immunotherapy. Also, the aggressiveness of the autoimmune reactions depends on the patient's immune state and its reactivity.

Objective: The present study includes pharmacophore hypothesis, 3D QSAR, virtual screening, docking, ADME analysis, and screening of potential imidazo[1,5-a]pyrazine derivatives as BTK inhibitors.

Methods: Generation of pharmacophore hypothesis, virtual screening, 3D QSAR, molecular docking, and ADME analysis were conducted.

Results: The pharmacophore study generated 20 pharmacophore hypotheses as BTK inhibitors. The five-point hypothesis DPRRR_1 was selected, consisting of one hydrogen bond donor, one positive ionic, and three-ring aromatic features. 3D QSAR study of the compounds provided the best model with high Q2 (0.8683), R2 (0.983), and R2CV (0.5338) values. The developed pharmacophore model was further taken for screening of ZINC database ligands for evaluation of docking interaction and physiochemical properties. Potent compounds of the series 15, 27, 8n, and 38 showed good docking scores -8.567, -7.465, -6.922, -6.137, respectively.

Conclusion: All the pharmacokinetic parameters analyzed, including human oral absorption of active compounds of the series, were found to be within the permissible range. The present geometry and features included in the pharmacophore hypothesis can be used for the development of novel BTK inhibitors as anticancer agents.

Additionally, we discuss the future prospects of PET radiometals production in the liquid targets for academic research and clinical applications. Significant emphasis has been given to the production of ⁶⁸Ga using liquid targets due to the growing demand for ⁶⁸Ga labeled PSMA vectors, [⁶⁸Ga]- Ga-DOTATATE, [⁶⁸Ga]Ga-DOTANOC and some upcoming ⁶⁸Ga labeled radiopharmaceuticals. Other PET radiometals included in the discussion are ⁸⁶Y, ⁶³Zn and ⁸⁹Zr.

Methods: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage.

Results: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage.

Conclusion: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Case Presentation: We describe the Magnetic Resonance Imaging (MRI) features of a case of uterovaginal diffuse large B-cell lymphoma in a 50-year-old postmenopausal woman emphasizing Diffusion-Weighted Imaging (DWI) as a diagnostic and follow up tool. We reviewed the literature regarding the diagnostic methods for female genital lymphoma. Forty-five cases, including our patient, were reviewed with an age range from 22 to 85 years. Vaginal bleeding was the most common presentation. The diagnosis was established by Papanicolaou smear, cervical biopsy (25/45), endometrial biopsy (6/45), vaginal biopsy (2/45), pelvic mass biopsy (2/45), iliac LN biopsy (1/45) and surgical diagnosis (8/45). Diffuse Large B-Cell Lymphomas (DLBCL) constitute the vast majority of the cases (82%). The uterine cervix was involved at diagnosis in the majority of these cases (68%), while the uterine body (42%) and vagina (28%) were less involved. Pelvic lymphadenopathy was found in 15 cases, while extra genital lymphomatous infiltration in 13 cases. Sonographic findings were nonspecific, while CT provided excellent data about extra-genital involvement. Thirteen cases underwent pelvic MRI that displayed superior detection of disease extension and parametric involvement. Diffusion restriction was reported only in one case without quantitative analysis of ADC map.

Conclusion: MRI shows unique features that differentiate uterovaginal lymphoma from the much more common carcinomas and discriminate post-operative changes from tumor recurrence. It exhibits a marked restricted diffusion pattern with lower ADC values than carcinomas and post-operative changes.

Objective: We aim to label and evaluate Fab(Tocilizumab) with ^99mTechnetium or Cy7 as potential MM imaging agents.

Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with ^99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h.

Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with 99mTc via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i.

Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.

Objective: To find a potential peptide inhibitor against MMP9, which, in turn, could inhibit MCL progression.

Methods: We performed CCK8 assay, western blot, and transwell assays for RNAi activity. Molecular Operating Environment (MOE) software was applied for structural optimization as MMP9 and peptides were docked. We used gelatin zymography and confocal microscopy to confirm that the peptides can inhibit MMP9 activity. We applied CCK8 and transwell assay to evaluate cell proliferation and metastasis, and flow cytometry to evaluate cell cycle progression and apoptosis.

Results: High MMP9 expression was observed in 49 of 88 samples (55.7%). Patients with high MMP9 expression were more likely to present with high stage (Stage 3-4, P=0.01), bone marrow invasion (P=0.033), and high-level LDH (P=0.000). High MMP9 expression was associated with significantly shorter overall survival (OS, HR=2.378, P=0.012) and progression-free survival (PFS, HR=2.068, P=0.03). Multivariate analysis identified high MMP9 expression (P= 0.027), high-risk mantle cell lymphoma international prognostic index (MIPI, HR=2.327, P=0.023), and no radiation therapy (P=0.035) as adverse prognostic factors. The silencing of MMP9 in Jeko-1 cells by RNAi suppressed cells migration and invasion in vitro (P<0.05). According to the docking results, peptide M3 bound deeply in the binding pocket of MMP9 and had interaction with the active-site Zn²⁺ ion in the catalytic domain. M3 was not only compatible with MMP9, but also inhibited its activity. M3 inhibited Jeko-1 cells proliferation, metastasis, and cell cycle progression, and promoted cell apoptosis rate (P<0.05).

Conclusion: We designed M3 through structure-based molecular docking, which can specifically bind to MMP9 and inhibit the activity of MMP9. M3 could be a potential antagonist in the treatment of MCL with MMP9 overexpression.

Objective: This review focuses on the analysis of the nanoformulations that are under clinical research in the treatment of these neoplasms.

Results: Currently, there are 6 nanoformulations in clinical trials for breast and ovarian carcinomas, most of them in phase II and phase III. In the case of breast cancer treatment, these nanomedicines contain paclitaxel; and, for ovarian cancer, nanoformulations containing paclitaxel or camptothecin analogs are being evaluated. The nanoencapsulation of these antineoplastics facilitates their administration and reduces their systemic toxicity. Nevertheless, the final approval and commercialization of nanoformulations may be limited by other aspects like lack of correlation between the efficacy results evaluated at in vitro and in vivo levels, difficulty in producing large batches of nanoformulations in a reproducible manner and high production costs compared to conventional formulations of antineoplastics. However, these challenges are not insurmountable and the number of approved nanoformulations for cancer therapy is growing.

Conclusion: Reviewed nanoformulations have shown, in general, excellent results, demonstrating a good safety profile, a higher maximum tolerated dose and a similar or even slightly better antitumor efficacy compared to the administration of free drugs, reinforcing the use of nano-chemotherapy in both breast and ovarian tumors.

Aim: The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1 and determine the most suitable and effective protein target for the MCL.

Methodology: Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds.

Result: MMP9 inhibitors show commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore study of the best virtual screened compound reveals its high efficacy based on various interactions. The virtual screened compound's better affinity with the target MMP9 protein was deduced using toxicity and integration profile studies.

Conclusion: Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with LD50 values for both the compounds lying in the same range.

Objective: This review summarizes the research progress and development direction of PAMP adjuvants, focusing on their immune mechanisms and clinical applications.

Methods: PubMed, Scopus, and Google Scholar were screened for this information. We highlight the immune mechanisms and clinical applications of PAMP adjuvants.

Results: Because of the differences in receptor positions, specific immune cells targets, and signaling pathways, the detailed molecular mechanism and pharmacokinetic properties of one agonist cannot be fully generalized to another agonist, and each PAMP should be studied separately. In addition, combination therapy and effective integration of different adjuvants can increase the additional efficacy of innate and adaptive immune responses.

Conclusion: The mechanisms by which PAMPs exert adjuvant functions are diverse. With continuous discovery in the future, constant adjustments should be made to build new understandings. At present, the goal of therapeutic vaccination is to induce T cells that can specifically recognize and eliminate tumor cells and establish long-term immune memory. Following immune checkpoint modulation therapy, cancer treatment vaccines may be an option worthy of clinical testing.

Introduction: The increase in the number of hematological malignancy-related cases in our modern society urges suitable treatment of such disease. In this current era, there is still a major deficiency in the number of suitable chemotherapeutic agents for the treatment of hematological malignancies.

Methods: The researchers were successful in identifying various cellular, extracellular proteins, and cytokines, as well as their involvement in different hematological malignancies via epigenetic modulation and regulation of other proteins and signaling pathways. Here, we have discussed the structural aspects, connection, and pathophysiological contributions of a group of different cellular and extracellular proteins that are regulated and/or have a significant influence on the progression of different hematological malignancies along with their potent inhibitors.

Result and Conclusion: The correlation of physiological proteins with cancerous hematological conditions has been discussed here. It can be crucial for the development of potent inhibitors as chemotherapeutic agents to contest such malignancies. This review will also be useful in the chemotherapeutic agent development by providing crucial information about such hematological malignancy-related proteins and their inhibitors. The repurposed drugs with potential for anticancer applications are also discussed.

Case: Here we present the case of PTLD Burkitt's Lymphoma (BL-PTLD) in a renal transplant patient who was successfully treated with multiagent chemo-immunotherapy but later developed BK polyomavirus nephropathy (BKVN) with graft failure only after completion of her systemic therapy for lymphoma and 7 years after the transplant. Relevant literature is reviewed.

Conclusion: In this case, reactivation and progression of BKVN were most likely associated with immunosuppression from chemo-immunotherapy for her BL–PTLD, unlike early graft failures associated with BKVN.

Objective: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and progression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and microRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel, well-suited approaches against ALL.

Conclusion: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifications, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

Objectives: The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends.

Results: We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables.

Conclusion: The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.

Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway.

Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression.

Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats’ cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively.

Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor.

Conclusion: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Methods: KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues.

Results: The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which received the drug through the current designed delivery system.

Conclusion: The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.

Objective: Here, an effort was made to outline the recent findings deciphering the new molecular mechanisms involved in the regulation of ubiquitin-proteasome pathway as well as the resistance mechanisms developed against proteasome inhibitors in cell culture experiments and in the clinical trials.

Results: Since cancer cells have higher proliferation rates and are more prone to translational errors, they require the ubiquitin-proteasome pathway for selective advantage and sustained proliferation. Therefore, drugs targeting the ubiquitin-proteasome pathway are promising agents for the treatment of both hematological and solid cancers.

Conclusion: A number of proteasome inhibitors are approved and used for the treatment of advanced and relapsed multiple myeloma. Unfortunately, drug resistance mechanisms may develop very fast within days of the start of the proteasome inhibitor-treatment either due to the inherent or acquired resistance mechanisms under selective drug pressure. However, a comprehensive understanding of the mechanisms leading to the proteasome inhibitor-resistance will eventually help the design and development of novel strategies involving new drugs and/or drug combinations for the treatment of a number of cancers.

Objective: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset.

Methods: To collect the scientific evidences regarding this topic the keywords “light alcohol drinking”, “light alcohol consumption” and “cancer”, were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded.

Results: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma.

Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed.

Conclusion: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.

Objective: The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL.

Methods: This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient’s characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated.

Results: EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis.

Conclusion: Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.

Case Presentation: Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma.

Conclusion: Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.

Methods: In this study, the gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were highly related to drugs for leukemia were investigated for the first time. The enrichment scores for associated GO terms and KEGG pathways were calculated to evaluate the drugs and leukemia. The feature selection method, minimum redundancy maximum relevance (mRMR), was used to analyze and identify important GO terms and KEGG pathways.

Results: Twenty Go terms and two KEGG pathways with high scores have all been confirmed to effectively distinguish four types of leukemia.

Conclusion: This analysis may provide a useful tool for the discrepant pathogenesis and drug design of different types of leukemia.

Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care.

Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases.

Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce.

Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.

Methods: We queried PubMed, Web of Science, Google Scholar, Science Direct and Scopus databases with keywords pertaining to Hu5F9-G4. In addition, we have included the Hu5F9-G4 data presented at the 60th American Society of Hematology (ASH) Annual Meeting, the American Society of Clinical Oncology (ASCO) Annual Meeting and 23rd Congress of the European Hematology Association (EHA).

Results: We discuss the mechanistic basis and preclinical evidence for the anticancer activity of Hu5F9-G4. Further, we delineate clinical studies, alone and in combination with anti-CD20 mAb rituximab, anti-EGFR mAb cetuximab, PD-L1 checkpoint inhibitors avelumab and atezolizumab, and anti-HER2 mAb trastuzumab. Moreover, the potential adverse effects, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 with emphasis on the role of CD47-SIRPα signaling in phagocytosis are presented.

Conclusion: Taken together, we review the pharmacokinetics and systems pharmacology of Hu5F9-G4 which appears to hold great promise for the future of cancer care.

Objective: The current review aims to present a brief overview of signal pathways of DLBCL, which mainly focus on B-cell antigen Receptor (BCR), Nuclear Factor-κB (NF-κB), Phosphatidylinositol-3-Kinase (PI3K) – protein kinase B (Akt) – mammalian Target of Rapamycin (mTOR), Janus Kinase (JAK) – Signal Transducer and Activator (STAT), Wnt/β-catenin, and P53 pathways.

Methods: Activation of signal pathways may contribute to the generation, development, chemotherapy sensitivity of DLBCL, and expression of pathway molecules is associated with the prognosis of DLBCL. Some agents targeting these pathways have been proved effective and relevant clinical trials are in progress. These agents used single or combined with chemotherapy/each other might raise the possibility of improving clinical outcomes in DLBCL.

Conclusion: This review presents several signal pathways of DLBCL and targeted agents had a tendency to improve the curative effect, especially in high-risk or relapsed/refractory DLBCL.

Materials and Methods: Using the HTS technique, nearly 3,800 clinically approved drugs and drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the selectivity window of the candidate compounds in six normal cell lines. Further validations were performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates model using Z138 cell line.

Results: We identified 98 compounds showing >50% inhibition in either MCL cell line screened, they were distributed across eight unique therapeutic categories and have different mechanisms of action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and drug developing stages in terms of clinical research. Alisertib and carfilzomib showed antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We further validated and demonstrated their anti-MCL effect on cell proliferation and (3D) multicellular aggregates model using Z138 cell line.

Conclusion: This is the first study to examine such a large library of clinically approved compounds for the identification of novel drug candidates for MCL treatment, the results could be rapidly translated into clinical practice in patients with MCL.

Methods: Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were collected from left ventricular areas at different time points. To determine whether MIF supplementation is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression.

Results: The expression of MIF was remarkably higher in obese group compared to lean group. Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced the infarct size in lean mice only.

Conclusion: An impaired MIF/AMPK activation response and consequent reduced membrane Glut4 expression may play an important role in increasing myocardial susceptibility to I/R in obesity.

Objective: In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR).

Materials and Methods: In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR).

Results: Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments.

Conclusion: Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.

Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific T-cell engagers, adoptive T-cell approaches and cancer vaccines have joined the platform so far, represented mainly by recombinant cytokines, therapeutic monoclonal antibodies and immunomodulatory agents. In specific clinical indications, conventional drugs have already been supplanted by multi-agent, chemotherapy-free regimens comprising diverse immunotherapy and/or targeted agents. The very distinct mechanisms of the anticancer activity of new immunotherapy approaches not only call for novel response criteria, but might also change fundamental treatment paradigms of certain types of hematologic malignancies in the near future.

Methods: This cross-sectional study was conducted over a 3-year period from July 2013 to June 2016, wherein successive HIV positive patients from an anti-retroviral therapy (ART) center were screened for malignancy. Simultaneously, successive cancer patients at the cancer center were screened for HIV. Baseline demographic details, risk factors, and laboratory investigations were obtained for all the patients.

Results: Among the 999 HIV-positive patients at the ART center, the prevalence of malignancy was 2% (n=20; 95% confidence interval (CI) 1.13, 2.87). Among the 998 patients with a malignancy, the prevalence of HIV infection was 0.9% (n=9; 95% CI 0.31, 1.49). Weight loss, loss of appetite, and fever were the most common symptoms in patients with HIV and cancer. Among 29 patients with HIV and cancer, AIDS-defining cancer was found in 19 patients; non-Hodgkin’s lymphoma was the most common malignancy reported (n=13).

Interpretation and Conclusion: There is a low prevalence of HIV in cancer patients as well as a low prevalence of cancer in HIV patients. AIDS-defining cancers remain much more common than non-AIDS-defining cancers. With the increased coverage of ART, it is expected that non-AIDSdefining cancers will increase, as is evident from data from more developed countries.]]> https://www.benthamscience.comarticle/86341

Objective: This review aims to provide an overview on the characterization of CECs and EPCs, to describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation.

Methods: We performed a detailed search of peer-reviewed literature using keywords related to CECs, EPCs, allogeneic hematopoietic stem cell transplantation, and hematological diseases (hemoglobinopathies, hodgkin and non-hodgkin lymphoma, acute leukemia, myeloproliferative syndromes, chronic lymphocytic leukemia).

Results: CECs and EPCs are potential biomarkers for several clinical conditions involving endothelial turnover and remodeling, such as in hematological diseases. These cells may be involved in disease progression and in the neoplastic process. Moreover, CECs and EPCs are probably involved in endothelial damage which is a marker of several complications following allogeneic hematopoietic stem cell transplantation.

Conclusion: This review provides information about the role of CECs and EPCs in hematological malignancies and shows their implication in predicting disease activity as well as improving HSCT outcomes.]]> https://www.benthamscience.comarticle/93125 https://www.benthamscience.comarticle/88997

Objective: The current review aims to provide information on recent advancements in clinical developments of antibodies against glycan-binding proteins as potential targets.

Results and Conclusion: There are several therapeutic antibodies being developed targeting glycanbinding proteins, including CD22, CD33, DEC-205, and CD62P, for different diseases. The clinical investigations demonstrated benefits of treatments with one antibody-drug conjugate against CD22 being approved by the regulatory agencies. The recent progresses in clinical developments of these antibodies have provided great promises in therapeutic targeting of more glycan-binding proteins for treating multiple diseases, including inflammation, autoimmune diseases, and hematological malignancies.]]> https://www.benthamscience.comarticle/92895 https://www.benthamscience.comarticle/88898

Objective: In this review, a brief update on cancer, its causes and different types has been discussed along with updated statistics of patient's mortality. A brief overview of cervical cancer and its pathophysiology has been discussed with special emphasis on its causative agent, human papilloma virus (HPV). A brief introduction and update on genetics, molecular pathogenesis and prevalence of HPV and its role in cervical cancer have been added.

Conclusion: This review delivered an updated status of cervical cancer and provide novel therapeutic approaches for targeting HPV. The detailed molecular and genomic information of the HPV help the researchers to develop more effective and efficacious therapeutic strategies and preventive vaccines that will significantly contribute to the control and anticipation of cervical cancer. Ultimately this may open new vistas to get rid of this deadly disease and may offer significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer in the affected nations.]]> https://www.benthamscience.comarticle/89704

Methods: A total of 461 patients (311 males and 150 females) with PADs enrolled in the retrospective cohort study and for all patients’ demographic information, clinical records and laboratory data were collected to investigate clinical complications.

Results: The most prevalent first presentations of immunodeficiency were respiratory tract infections in 63.5% and chronic diarrhea in 17.2%. Common variable immune deficiency (CVID) patients had a higher diagnostic delay than class switching defect (CSD), and agammaglobulinemia. Among the noninfectious complications, autoimmunity (26.2%), and splenomegaly (23.4%) were the most common. Lymphadenopathy was higher in CSD patients than other PADs, while splenomegaly, hepatomegaly, autoimmunity and bronchiectasis were more common in CVID patients than others. Atopic manifestations were mostly recorded in patients with selective IgA deficiency. Malignancy was only reported in 5.8% of patients with CVID. There was a higher prevalence of autoimmune manifestations in CVID comparing to other PADs.

Conclusion: PADs are relatively rare diseases and these patients have a variety of first clinical manifestations, such as diverse infections, autoimmunity, lymphoproliferation, allergy, enteropathy and malignancy. Practitioner’s awareness about the heterogeneous presentations of PAD disorders is poor, therefore patients often are lately diagnosed, and they are complicated with several clinical complications before the certain diagnosis.]]> https://www.benthamscience.comarticle/90536

Methods: In a phase 1 study, 76 patients with relapsed/refractory NHL received blinatumomab by continuous intravenous infusion at various doses (0.5 to 90 µg/m2/day). PD changes were analyzed with respect to dose, blinatumomab concentration at steady state (Css), and cumulative area under the concentration-versus-time curve (AUCcum).

Results: B-cell depletion occurred within 48 hours at doses ≥5 µg/m2/day, followed first-order kinetics, and was blinatumomab exposure-dependent. Change in tumor size depended on systemic blinatumomab exposure and treatment duration and could be fitted to an Emax model, which predicted a 50% reduction in tumor size at AUCcum of ≥1,340 h×µg/L and Css of ≥1,830 pg/mL, corresponding to a blinatumomab dose of 47 µg/m2/day for 28 days. The magnitude of transient cytokine elevation, observed within 1-2 days of infusion start, was dose-dependent, with less pronounced elevation at low starting doses.

Conclusion: B-lymphocyte depletion following blinatumomab infusion was exposure-dependent. Transient cytokine elevation increased with dose; it was less pronounced at low starting doses. Tumor response was a function of exposure, suggesting utility for the PK/PD relationship in dose selection for future studies, including NHL and other malignant settings.]]> https://www.benthamscience.comarticle/90808 https://www.benthamscience.comarticle/80696 https://www.benthamscience.comarticle/85020 https://www.benthamscience.comarticle/86867

Materials and Methods: Monophosphate analogs of fludarabine, gemcitabine, and dexamethasone were combined with a carbodiimide reagent in the presence of imidazole to produce reactive intermediates that were subsequently covalently bound to monoclonal anti-IGF-1R or anti-EGFR IgG-immunoglobulin. The resulting covalent immunopharmaceutical end-products, fludarabine-(5'-phosphoramidate)-[anti-IGF-1R], gemcitabine-(5'- phosphoramidate)-[anti-IGF-1R], and dexamethasone-(C21-phosphoramidate)-[anti-EGFR] were evaluated by SDS-PAGE/chemiluminescent autoradiography (fragmentation/polymerization detection), UV spectrophotometric absorbance (purity; molar-incorporation-index), cell-ELISA (retained selective binding-avidity), and cell vitality-viability (selectively “targeted” anti-neoplastic cytotoxicity).

Results: Maximum selectively “targeted” anti-neoplastic cytotoxicity of fludarabine-(5'-phosphoramidate)-[anti- IGF-1R], gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R], and dexamethasone-(C21-phosphoramidate)-[anti- EGFR] was detected at the pharmaceutical-equivalent concentrations of 10-5 M (94.7%), 10-7 M (93.1%), and 10-7 M (64.9%) respectively.

Discussion: Organic chemistry reactions were optimized in a template multi-stage synthesis regimen for fludarabine-( 5'-phosphoramidate)-[anti-IGF-1R], gemcitabine-(5’-phosphoramidate)-[anti-IGF-1R], and dexamethasone-( C21-phosphoramidate)-[anti-EGFR]. Attributes of the synthesis regimen include; [-i-] covalent bonding of pharmaceutical moeities at high molar incorporation indexes, [-ii-] implementation of organic chemistry reactions in a non-dedicated synthesis regimen allowing component substitution and [-iii-] optional preservation of presynthesized amine-reactive pharmaceutical intermediates for on-demand immunopharmaceutical synthesis. Attributes of the covalent immunopharmaceuticals are; absence of any synthetically introduced chemical groups, retained IgG-immunoglobulin binding-avidity and potent selective “targeted” anti-neoplastic cytotoxic potency. Under in-vivo conditions, supplemental anti-neoplastic cytotoxicity is realized through trophic receptor inhibition and activation of multiple cytotoxic host immune responses.]]> https://www.benthamscience.comarticle/87251

Objective and Methods: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women.

Results: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence.

Conclusion: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.]]> https://www.benthamscience.comarticle/89803

Methods: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or nonviral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.

Results: Clinical trials have shown very promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors.

Conclusion: In this review, the basic design of CARs, the main genetic modification strategies, the safety matters as well as the initial clinical experience with CAR T-cells are described.]]> https://www.benthamscience.comarticle/88015

Methods: A large pore amine functionalized MSN (MSNs-NH2) is described here to facilitate delivery of clarithromycin (CLM) as an antibacterial drug and enhance the efficacy against Gram positive and Gram negative bacterial samples. Prepared particles were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), nitrogen adsorption/ desorption isotherms, Fourier Transform Infrared (FT-IR) spectroscopy and X-ray Diffraction (XRD) spectroscopy. The antimicrobial activity was evaluated by agar well diffusion and broth dilution methods. Therefore, the biodistribution of FITC-MSNs was investigated by measure the NIR intensity fluorescent of fluorescent images from whole animal and dissected organs of NMRI mice.

Results: The results showed that the CLM loaded MSNs-NH2 (CLM/MSNs-NH2) were successfully prepared having good payload and pH-sensitive drug release kinetics. The antimicrobial investigation against Staphylococcus aureus and Escherichia coli was showed better performance of antimicrobial activity of these nanoparticles. In vivo and ex vivo fluorescent imaging investigation on NMRI mice were shown that FITC-MSNs-NH2 accumulated in the liver and kidney and notably in lung tissue.

Conclusion: The CLM/MSNs-NH2 exhibited higher antimicrobial activity and enhanced the possibility of microbial infection therapy especially at respiratory infections.]]> https://www.benthamscience.comarticle/87141

More in detail, neoplastic tissues of patients should display a specific biomarker, most often a specific genetic alteration and/or under/overexpression of a definite protein, that could be the target of its respective drug. Immunohistochemical and molecular analyses, which usually include examination of nucleic acids from either tissues or fluids, are common tests to define the status of a tumor.

This review focuses on the pathologist’s role in carefully controlling pre- analytic procedures and standard operating procedures that are a crucial prerequisite to reach reliable and reproducible results. Six paradigmatic applications of targeted therapy, for which pathological diagnosis plays a fundamental role, are summarized. Traditional and next-generation sequencing are also addressed from the pathologist's perspective as well as the importance pathologists have in this shift to more accurate definition of disease risk and prognostication of therapy response in the personalized medicine era.]]> https://www.benthamscience.comarticle/80608

Methods: We undertook a structured search of bibliographic database for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to analyze the interventions and findings of included studies using a conceptual framework.

Results: Twenty-one papers were included in the review, eight papers outlined the relationship of Cx43 and reperfusion arrhythmias. Eight papers pointed out the effect on the infarct size of Cx43.

Conclusion: The findings of this review confirm that Cx43 is the most abundant member of Cx family in the heart and is vital for myocardial protection during ischemia/reperfusion process and for ischemia/reperfusion injury. Many of its mechanism are still not very clear and require future research in the future.]]> https://www.benthamscience.comarticle/87896 https://www.benthamscience.comarticle/86018

In this review, we first summarize two key learnings from the initial studies of inhibitors of this pathway, including the profile of immune-related adverse events such as colitis, transaminitis and pneumonitis and the increased incidence of infections with the majority of agents that target the PI3K-AKT-mTOR pathway. We then discuss recent advances in our understanding of the role of this pathway in the tumour micro-environment, and in the regulation of innate and adaptive immune responses, and propose synergistic combination strategies with PI3K-network inhibitors and cancer immunotherapy.]]> https://www.benthamscience.comarticle/89543 https://www.benthamscience.comarticle/87339

Objectives: Although the use of this radionuclide has grown exponentially over the last decade, academic institutions have largely been responsible for its production and for the development of the vast majority of radiopharmaceutical based on these nuclides. A number of compounds labelled with Cuisotopes have been proposed, not only for imaging purposes but also for therapy. The aim of the present paper is to provide an overview on the clinical results obtained in human beings with copper radionuclides.

Conclusion: Several preliminary studies and clinical trials evaluated the potential clinical role of copper radioisotopes for diagnostic and therapeutic purposes. 64Cu seems to be the most suitable radioisotope for future clinical applications due to its longer half-life (12.7 h) and its commercial availability. Future clinical applications of copper radioisotopes could be enhanced by the possibility of radioligand therapy with the beta-emitting 67Cu, creating a new “theranostics pair”.]]>