Microfluidic System Consisting of a Magnetic 3D-Printed Microchannel Filter for Isolation and Enrichment of Circulating Tumor Cells Targeted by Anti-HER2/MOF@Ferrite Core-Shell Nanostructures: A Theranostic CTC Dialysis System.

Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel in situ core-shell Cu ferrites consisting of the Cu-CuFe2O4 core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/Fe3O4 nanoparticle composite with pore diameter less than 200 µm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.

An unusual presentation of metastatic prostate cancer in a 44-year-old man: A case report and review of the literature.

Prostate cancer is one of the two most common non-cutaneous cancers in men. Its presentation might be with unusual symptoms and cause the wrong initial diagnosis. This case report discusses a rare neurologic manifestation of advanced metastatic cancer in a low-risk man. He had been receiving treatment for multiple sclerosis incorrectly due to unusual manifestations such as claudication and pelvic, leg, and shoulder pain. The patient underwent a whole-body bone scan and then a transrectal ultrasound-guided biopsy, which confirmed metastatic prostate cancer with a Gleason score between 7/10 and 10/10 in all samples. Following treatment with chemotherapeutic injections (docetaxel), luteinizing hormone-releasing hormone (LHRH) analogous (Zoladex), and testosterone-suppressing tablets (abiraterone), the disease has been under control and prostate-specific antigen (PSA) level has decreased significantly. The most common sites of metastasis are regional lymph nodes, bones, and lungs. However, there are reports about the spread of this type of cancer to other parts of the body. Although most patients are diagnosed when the tumor is localized to the prostate, in about 25% of patients, the disease is diagnosed when metastasis has occurred. Some markers can assist physicians in the diagnosis of this disease, such as the Prostate Health Index and the 4 K score. Key Clinical Message: The diagnosis of prostate cancer should be considered in all age ranges of adult men. The long-distance metastasis might cause unusual presentations of the disease, such as neurologic, musculoskeletal, and dermatologic symptoms and signs far from the origin of the cancer, before genitourinary manifestations. It is crucial to keep the diagnosis of prostate cancer in mind for men with suggestive signs and symptoms that are not usually detected in this disease.

Challenges and Opportunities of Using Fluorescent Metal Nanocluster-Based Colorimetric Assays in Medicine.

Development of rapid colorimetric methods based on novel optical-active metal nanomaterials has provided methods for the detection of ions, biomarkers, cancers, etc. Fluorescent metal nanoclusters (FMNCs) have gained a lot of attention due to their unique physical, chemical, and optical properties providing numerous applications from rapid and sensitive detection to cellular imaging. However, because of very small color changes, their colorimetric applications for developing rapid tests based on the naked eye or simple UV-vis absorption spectrophotometry are still limited. FMNCs with peroxidase-like activity have significant potential in a wide variety of applications, especially for point-of-care diagnostics. In this review, the effect of using various capping agents and metals for the preparation of nanoclusters in their colorimetric sensing properties is explored, and the synthesis and detection mechanisms and the recent advances in their application for ultrasensitive chemical and biological analysis regarding human health are highlighted. Finally, the challenges that remain as well as the future perspectives are briefly discussed. Overcoming these limitations will allow us to expand the nanocluster's application for colorimetric diagnostic purposes in medical practice.

Highly improved pH-Responsive anticancer drug delivery and T2-Weighted MRI imaging by magnetic MOF CuBTC-based nano/microcomposite.

Cu-BTC framework has received a considerable attention in recent years as a drug carrier candidate for cancer treatment due to its unique structural properties and promising biocompatibility. However, its intrinsic deficiency for medical imaging potentially limits its bioapplications; To address this subject, a magnetic nano/microscale MOF has been successfully fabricated by introducing Fe3O4 nanoparticles as an imaging agent into the porous isoreticular MOF [Cu3(BTC)2] as a drug carrier. The synthesized magnetic MOFs exhibits a high loading capacity (40.5%) toward the model anticancer DOX with an excellent pH-responsive drug release. The proposed nanocomposite not only possesses large surface area, high magnetic response, large mesopore volume, high transverse relaxivity (r 2) and good stability but also exhibits superior biocompatibility, specific tumor cellular uptake, and significant cancer cell viability inhibitory effect without any targeting agent. It is expected that the synthesized magnetic nano/microcomposite may be used for clinical purposes and can also serve as a platform for photoactive antibacterial therapy ae well as pH/GSH/photo-triple-responsive nanocarrier.

Potential anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on B16-F10 murine melanoma: In vitro and in vivo studies.

Melanoma is the major type of skin cancer, which its treatment is still a challenge in the world. In recent years, interest in hibernation-based therapeutic approaches for various biomedical applications has been increased. Many studies indicated that some factors in the blood plasma of hibernating animals such as alpha-2-macroglobulin (A2M) cause anti-proliferative effects. Considering that, the present study was conducted to investigate the anti-cancer effects of hibernating common carp plasma (HCCP) on murine melanoma (B16-F10) in vitro and in vivo. The effect of HCCP on cell viability, migration, apoptosis rate, and cell cycle distribution of B16-F10 cells, tumor growth, and rate of survival were evaluated. To investigate the role of A2M in the anti-cancer effects of HCCP, the gene of interest and proteins in HCCP and non-hibernating common carp plasma (NHCCP) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry analysis. Based on our findings, HCCP significantly decreased B16-F10 cell viability. Moreover, HCCP caused morphological alternations, inhibition of migration, induction of apoptosis, and significantly induced the cell cycle arrest at the G2/M phase. In addition, A2M level was significantly increased in HCCP compared with NHCCP. Taken together, our findings suggested that HCCP had the potential to be a promising novel therapeutic target for cancer treatment because of its anti-cancer properties.

Role of the Probe Sequence/Structure in Developing an Ultra-Efficient Label-Free COVID-19 Detection Method Based on Competitive Dual-Emission Ratiometric DNA-Templated Silver Nanoclusters as Single Fluorescent Probes.

We report the development of a label-, antibody-, enzyme-, and amplification-free ratiometric fluorescent biosensor for low-cost and rapid (less than 12 min) diagnosis of COVID-19 from isolated RNA samples. The biosensor is designed on the basis of cytosine-modified antisense oligonucleotides specific for either N gene or RdRP gene that can form silver nanoclusters (AgNCs) with both green and red emission on an oligonucleotide via a one-step synthesis process. The presence of the target RNA sequence of SARS-CoV-2 causes a dual-emission ratiometric signal transduction, resulting in a limit of detection of 0.30 to 10.0 nM and appropriate linear ranges with no need for any further amplification, fluorophore, or design with a special DNA fragment. With this strategy, five different ratiometric fluorescent probes are designed, and how the T/C ratio, the length of the stem region, and the number of cytosines in the loop structure and at the 3' end of the cluster-stabilizing template can affect the biosensor sensitivity is investigated. Furthermore, the effect of graphene oxide (GO) on the ratiometric behavior of nanoclusters is demonstrated and the concentration-/time-dependent new competitive mechanism between aggregation-caused quenching (ACQ) and aggregation-induced emission enhancement (AIE) for the developed ssDNA-AgNCs/GO nanohybrids is proposed. Finally, the performance of the designed ratiometric biosensor has been validated using the RNA extract obtained from more than 150 clinical samples, and the results have been confirmed by the FDA-approved reverse transcription-polymerase chain reaction (RT-PCR) diagnostic method. The diagnostic sensitivity and specificity of the best probe is more than >90%, with an area under the receiver operating characteristic (ROC) curve of 0.978.

Multifunctional Gold Helix Phototheranostic Biohybrid That Enables Targeted Image-Guided Photothermal Therapy in Breast Cancer.

The preparation of multifunctional smart theranostic systems is commonly achieved through complicated strategies, limiting their biomedical applications. Spirulina platensis (SP) microalgae, as a natural helix with some of the intrinsic theranostic functionalities (e.g., fluorescent and photosensitizer pigments), not only facilitates the fabrication process but also guarantees their biosafety for clinical applications. Herein, the helical architecture of gold nanoparticles (AuNPs) based on a SP biotemplate was engineered as a safe, biodegradable, and tumor-targeted biohybrid for imaging-guided photothermal therapy (PTT) to combat triple-negative breast cancer. The quasi-spherical AuNPs were embedded throughout the SP cell (Au-SP) with minimally involved reagents, only by controlling the original morphological stability of SP through pH adjustment of the synthesis media. SP thiolation increased the localization of AuNPs selectively on the cell wall without using a reducing agent (Au-TSP). SP autofluorescence, along with the high X-ray absorption of AuNPs, was employed for dual-modal fluorescence and computed tomography (FL/CT) imaging. Furthermore, the theranostic efficacy of Au-SP was improved through a targeting process with folic acid (Au-SP@CF). High tumor inhibition effects were obtained by the excellent photothermal performance of Au-SP@CF in both in vitro and in vivo analyses. Of particular note, a comparison of the photothermal effect of Au-SP@CF with the naked SP and calcined form of Au-SP@CF not only indicated the key role of the helical architecture of AuNPs in achieving a high photothermal effect but also led to the formation of new gold microspiral biohybrids (Au-MS) over the calcination process. In short, well-controllable immobilization of AuNPs, appropriate biodegradability, good hemocompatibility, long-term biosafety, accurate imaging, high tumor suppression, and low tumor metastasis effects under laser irradiation are an array of intriguing attributes, making the proposed biohybrid a promising theranostic system for FL/CT-imaging-guided PTT.

A 3D macroporous and magnetic Mg2SiO4-CuFe2O4 scaffold for bone tissue regeneration: Surface modification, in vitro and in vivo studies.

Macroporous scaffolds with bioactivity and magnetic properties can be a good candidate for bone regeneration and hyperthermia. In addition, modifying the surface of the scaffolds with biocompatible materials can increase their potential for in vivo applications. Here, we developed a multifunctional nanocomposite Mg2SiO4-CuFe2O4 scaffold for bone regeneration and hyperthermia. The surface of scaffold was coated with various concentrations of poly-3-hydroxybutyrate (P3HB, 1-5% (w/v)). It was observed that 3% (w/v) of P3HB provided a favorable combination of porosity (79 ± 2.1%) and compressive strength (3.2 ± 0.11 MPa). The hyperthermia potential of samples was assessed in the presence of various magnetic fields in vitro. The coated scaffolds showed a lower degradation rate than the un-coated one up to 35 days of soaking in simulated biological medium. Due to the porous and specific morphology of P3HB, it was found that in vitro bioactivity and cell attachment were increased on the scaffold. Moreover, it was observed that the P3HB coating improved the cell viability, alkaline phosphatase activity, and mineralization of the scaffold. Finally, we studied the bone formation ability of the scaffolds in vivo, and implanted the developed scaffold in the rat's femur for 8 weeks. Micro-computed tomography results including bone volume fraction and trabecular thickness exhibited an improvement in the bone regeneration of the coated scaffold compared to the control. The overall results of this study introduce a highly macroporous scaffold with multifunctional performance, noticeable ability in bone regeneration, and hyperthermia properties for osteosarcoma.

An in vitro and in vivo study of PCL/chitosan electrospun mat on polyurethane/propolis foam as a bilayer wound dressing.

In the current study, we fabricated a bilayer wound dressing consisting of an electrospun poly-ε-caprolactone/chitosan (PCL/CS) fibrous mat as the sublayer and a polyurethane (PU) foam coated with ethanolic extract of propolis (EEP) as the top layer. By blending the solutions of PCL and CS, we fabricated an electrospun mat consisting of bead-free and uniform nanofibers with enhanced hydrophilicity, swelling ratio, and degradation properties. To further enhance the mechanical and antibacterial properties, we electrospun the PCL/CS solution on a PU foam coated with EEP to fabricate the PCL/CS-PU/EEP bilayer wound dressing. Furthermore, the PCL/CS-PU/EEP bilayer wound dressing demonstrated enhanced cell compatibility and healing properties through in vitro and in vivo studies. Therefore, the PCL/CS-PU/EEP bilayer wound dressing offers great potential to be used as a wound dressing because of its suitable mechanical properties, swelling profile, antibacterial activity, biocompatibility, and wound healing properties.

Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment.

BACKGROUND: Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy, extensive first-pass effect, and low bioavailability. Therefore, multiple oral administration of high dose MBZ is required daily for achieving the therapeutic serum level which can cause severe side effects and patients' non-compliance. METHOD: In the present study, MBZ-loaded/folic acid-targeted chitosan nanoparticles (CS-FA-MBZ) were synthesized, characterized, and used to form cylindrical subcutaneous implants for 4T1 triple-negative breast tumor (TNBC) treatment in BALB/c mice. The therapeutic efficacy of the CS-FA-MBZ implants was investigated after subcutaneous implantation in comparison with Control, MBZ (40 mg/kg, oral administration, twice a week for 2 weeks), and CS-FA implants, according to 4T1 tumors' growth progression, metastasis, and tumor-bearing mice survival time. Also, their biocompatibility was evaluated by blood biochemical analyzes and histopathological investigation of vital organs. RESULTS: The CS-FA-MBZ implants were completely degraded 15 days after implantation and caused about 73.3%, 49.2%, 57.4% decrease in the mean tumors' volume in comparison with the Control (1050.5 ± 120.7 mm3), MBZ (552.4 ± 76.1 mm3), and CS-FA (658.3 ± 88.1 mm3) groups, respectively. Average liver metastatic colonies' number per microscope field at the CS-FA-MBZ group (2.3 ± 0.7) was significantly (P < 0.05) lower than the Control (9.6 ± 1.7), MBZ (5.0 ± 1.5), and CS-FA (5.2 ± 1) groups. In addition, the CS-FA-MBZ treated mice exhibited about 52.1%, 27.3%, and 17% more survival days after the cancer cells injection in comparison with the Control, MBZ, and CS-FA groups, respectively. Moreover, the CS-FA-MBZ implants were completely biocompatible based on histopathology and blood biochemical analyzes. CONCLUSION: Taking together, CS-FA-MBZ implants were completely biodegradable and biocompatible with high therapeutic efficacy in a murine TNBC model.

In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer.

Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.

Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches.

Recently, cancer immunotherapy has gained lots of attention to replace the current chemoradiation approaches and multi-epitope cancer vaccines are manifesting as the next generation of cancer immunotherapy. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a novel multi-epitope vaccine against breast cancer. The most immunogenic regions of the BORIS cancer-testis antigen were selected according to the binding affinity to MHC-I and II molecules as well as containing multiple cytotoxic T lymphocyte (CTL) epitopes by multiple immunoinformatics servers. The selected regions were linked together by GPGPG linker. Also, a T helper epitope (PADRE) and the TLR-4/MD-2 agonist (L7/L12 ribosomal protein from mycobacterium) were incorporated by A(EAAAK)3A linker to form the final vaccine construct. Then, its physicochemical properties, cleavage sites, TAP transport efficiency, B cell epitopes, IFN-γ inducing epitopes and population coverage were predicted. The final vaccine construct was reverse translated, codon-optimized and inserted into pcDNA3.1 to form the DNA vaccine. The final vaccine construct was a stable, immunogenic and non-allergenic protein that contained numerous CTL epitopes, IFN-γ inducing epitopes and several linear and conformational B cell epitopes. Also, the final vaccine construct formed stable and significant interactions with TLR-4/MD-2 complex according to molecular docking and dynamics simulations. Moreover, its world population coverage for HLA-I and HLA-II were about 93% and 96%, respectively. Taking together, these preliminary results can be used as an appropriate platform for further experimental investigations. Communicated by Ramaswamy H. Sarma.

Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model.

In our previous study, immunoinformatic tools were used to design a novel multiepitope cancer vaccine based on the most immunodominant regions of BORIS cancer-testis antigen. The final vaccine construct was an immunogenic, non-allergenic, and stable protein consisted of multiple cytotoxic T lymphocytes epitopes, IFN-γ inducing epitopes, and B cell epitopes according to bioinformatic analyzes. Herein, the DNA sequence of the final vaccine construct was placed into the pcDNA3.1 vector as a DNA vaccine (pcDNA3.1-VAC). Also, the recombinant multiepitope peptide vaccine (MPV) was produced by a transfected BL21 E. coli strain using a recombinant pET-28a vector and then, purified and screened by Fast protein liquid chromatography technique (FPLC) and Western blot, respectively. The anti-tumor effects of prophylactic co-immunization with these DNA and protein cancer vaccines were evaluated in the metastatic non-immunogenic 4T1 mammary carcinoma in BALB/c mice. Co-immunization with the pcDNA3.1-VAC and MPV significantly (P < 0.001) increased the serum levels of the MPV-specific IgG total, IgG2a, and IgG1. The splenocytes of co-immunized mice exhibited a significantly higher efficacy to produce interleukin-4 and interferon-γ and proliferation in response to MPV in comparison with the control. The prophylactic co-immunization regime caused significant breast tumors' growth inhibition, tumors' weight decrease, inhibition of metastasis formation, and enlarging tumor-bearing mice survival time, without any considerable side effects. Taking together, this cancer vaccine can evoke strong immune response against breast tumor and inhibits its growth and metastasis.

Polyurethane-Nanolignin Composite Foam Coated with Propolis as a Platform for Wound Dressing: Synthesis and Characterization.

This piece of research explores porous nanocomposite polyurethane (PU) foam synthesis, containing nanolignin (NL), coated with natural antimicrobial propolis for wound dressing. PU foam was synthesized using polyethylene glycol, glycerol, NL, and 1, 6-diisocyanato-hexane (NCO/OH ratio: 1.2) and water as blowing agent. The resultant foam was immersed in ethanolic extract of propolis (EEP). PU, NL-PU, and PU-NL/EEP foams were characterized from mechanical, morphological, and chemical perspectives. NL Incorporation into PU increased mechanical strength, while EEP coating showed lower strength than PU-NL/EEP. Morphological investigations confirmed an open-celled structure with a pore diameter of 150-200 µm, a density of nearly 0.2 g/cm3,, and porosity greater than 85%, which led to significantly high water absorption (267% for PU-NL/EEP). The hydrophilic nature of foams, measured by the contact angle, proved to be increased by NL addition and EEP coating. PU and PU-NL did not show important antibacterial features, while EEP coating resulted in a significant antibacterial efficiency. All foams revealed high biocompatibility toward L929 fibroblasts, with the highest cell viability and cell attachment for PU-NL/EEP. In vivo wound healing using Wistar rats' full-thickness skin wound model confirmed that PU-NL/EEP exhibited an essentially higher wound healing efficacy compared with other foams. Hence, PU-NL/EEP foam could be a promising wound dressing candidate.

Diagnostic and prognostic value of stem cell factor plasma level in glioblastoma multiforme patients.

BACKGROUND: Investigation of novel blood-circulating agents as potential biomarkers for glioblastoma multiforme (GBM) patients' diagnosis and monitoring has gained lots of attention, due to limitations of imaging modalities and invasive tissue biopsy procedures. The present study aims to assess the diagnostic and prognostic values of preoperative stem cell factor (SCF) plasma level in GBM patients. METHODS: Preoperative plasma samples from 58 GBM patients and 20 patients with nonglial tumors and 30 healthy controls were obtained. SCF levels were measured by employing the enzyme-linked immunosorbent assay test and the values were compared between these three groups. Then, the association of SCF plasma level and tumor volume, progression-free survival (PFS), and overall survival (OS) for the GBM patients were evaluated. RESULTS: Mean preoperative SCF plasma level of the GBM patients (2.80 ± 1.52 ng/ml) was significantly higher (p < 0.0001) than the healthy controls (0.80 ± 0.24 ng/ml) and patients with nonglial tumor (1.41 ± 0.76 ng/ml). Receiver operating characteristic analysis revealed that the preoperative SCF plasma level could distinguish the GBM patients from healthy controls and patients with nonglial tumors with the area under curve values of 0.915 and 0.790, respectively. However, no significant association was observed between the GBM patients' preoperative SCF plasma levels and tumors' volume (Spearman Rho correlation coefficient, 0.1847; 95% CI, p = 0.1652). The GBM patients were divided into two subgroups based on mean preoperative SCF plasma levels (2.80 ng/ml). No significant difference was observed between the patients' PFS (p = 0.3792) and OS (p = 0.1469) at these two subgroups. CONCLUSION: Taking together, the SCF plasma level can serve as a novel diagnostic blood-circulating biomarker for patients with GBM. However, its plasma level is not correlated with GBM patients' tumor volume, PFS, or OS.

Anti-cancer immunoprotective effects of immunization with hydatid cyst wall antigens in a non-immunogenic and metastatic triple-negative murine mammary carcinoma model.

Cancer vaccines have gained lots of attention as the future of cancer treatment. However, poor immunogenicity of tumor-associated antigens often fails to induce an efficient immune response against the tumor. Strange anti-tumor immune responses at the parasite-infected patients due to cross-reactivity have been reported in various studies. Therefore, parasite antigens with significant immunogenicity and high epitope homology with cancer antigens may activate a strong immune response against cancer cells. Herein, the sera of immunized rabbits with the hydatid cyst wall (HCW) antigens were incubated with 4 T1 mammary carcinoma cells to investigate cross-reactivity between the HCW antigens antisera and surface antigens of the breast cancer cells. Also, the SDS-PAGE profile of HCW antigens was prepared and incubated with the breast cancer patients' sera and considerable reactivity was observed between their sera and a specific band (~27/28 kDa) according to Western blotting analyzes. Then, the protein bands with cross-reactivity with breast cancer patients' sera were utilized for prophylactic immunizations of Balb/c mice. The immunoprotective effect of immunization with the HCW antigens caused significant inhibition of 4 T1 breast tumor growth, decrease of metastasis, and enlargement of the tumor-bearing mice survival time in comparison with PBS and pure immune adjuvant injected groups. Mass spectrometry analysis showed that the ~ 27/28 kDa band has numbers of proteins/polypeptides with a high degree of homology with cancer cells antigens which can be the reason for this cross-reactivity and anti-tumor immune response. Taking together, immunization with HCW antigens would be a promising approach in cancer immunotherapy after further investigations.

CD137: A Member of the TNFR Family - in Psoriasis Skin Lesions in Comparison with Normal Skin Specimens.

BACKGROUND & OBJECTIVE: CD137 is a member of the TNF-Receptor family. TNF-alpha antagonists have therapeutic effect in active psoriasis. In this study, the relative frequency of CD137 expression was investigated in the inflammatory cells of psoriasis lesions for the first time. METHODS: The specimens were obtained from pathology department of Al-Zahra hospital from paraffin-embedded skin specimens collected from 2007 till 2016. . A total number of f 64 psoriasis skin specimens and 34 normal skin specimens were reviewed for the diagnosis. Then, the immunohistochemical staining for CD137, CD4, and CD8 was performed. RESULTS: CD137 expression of dermal inflammatory cells in psoriasis lesions was 11.19±5.5%. Although, in normal skin tissues, CD137 expression was observed in 1.3±3.03% of the inflammatory cells. (P=0.001). The relative frequency of the CD137 positive inflammatory cells was significantly higher in the epidermis compared to dermis (epidermis: 31.1%±12.8, dermis 11.1%±5.5). There was no remarkable relation between the CD137 expression rate and the CD4: CD8 ratio. CONCLUSION: CD137 as a TNF-alpha receptor has a significant role in pathogenesis of the psoriasis lesions. Therefore, CD137 antagonists can be considered as a novel target for the treatment of incurable psoriasis patients.

A drug delivery system based on nanocomposites constructed from metal-organic frameworks and Mn3O4 nanoparticles: Preparation and physicochemical characterization for BT-474 and MCF-7 cancer cells.

An integrated nanocomposite system comprising of manganese oxide (Mn3O4) nanoparticles, functioning as a tumor diagnostic agent, in conjunction with polyacrylic acid (PAA) and ZIF-8, as pH-sensitive drug delivery agents, and methotrexate (MTX), operating as a tumor biomarker and a therapeutic agent (dual mechanism of action), is applied for both diagnostic intentions and controlled delivery of the drug. Physicochemical characteristics of the constructed system, Mn3O4@PAA@ZIF-8/MTX, are investigated by several methods, including X-ray diffraction, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and electrochemical techniques. The in-vitro magnetic resonance imaging measurements was performed to show the efficiency of Mn3O4@PAA@ZIF-8 nanocomposite as a contrast agent where a relaxivity (r1) of 3.3 mM-1 s-1 is found. The loading ratio was found as 161 % which is four times larger than the value obtained for Mn3O4@PAA system in the same conditions, indicating high capability of the system for MTX delivery. The application of the nanocomposite as a dual pH-sensitive nanocarrier for MTX is studied through in-vitro drug release experiments at pHs of 5.4, 6.8 and 7.4. Interestingly, the results show that a large amount of loaded MTX drug (53 %) is released from the system during incubation and dialysis at pH 5.4, compared with that (20 % and 15 %), respectively, released at pHs 6.8 and 7.4 at the same conditions. The affinity of Mn3O4@PAA@ZIF-8/MTX nanocomposite for capturing of BT-474 and MCF-7 cancer cells was evaluated via impedance spectroscopy measurements. The results show that GC-Mn3O4@PAA@ZIF-8/MTX electrode captures the BT-474 and MCF-7 cancer cells, respectively, by factors of ∼2 and 196 compared with L929 normal cells. This affinity also shows the high selectivity of the system for MCF-7 cancer cells compared with BT-474.

Efficacy of co-immunization with the DNA and peptide vaccines containing SYCP1 and ACRBP epitopes in a murine triple-negative breast cancer model.

Multiepitope cancer vaccines have gained lots of attention for prophylactic and therapeutic purposes in cancer patients. In our previous study, multiepitope DNA and peptide cancer vaccines consisted of the most immunodominant epitopes of ACRBP and SYCP1 antigens were designed by bioinformatic tools. In this study, the effect of prophylactic co-immunization with these DNA and peptide cancer vaccines in the 4T1 breast cancer animal model was assessed. Serum levels of the peptide-specific IgG total, IgG2a and IgG1 were measured by enzyme-linked immunosorbent assay (ELISA). Also, the efficacy of the immunized mice splenocytes' for producing interleukin-4 (IL-4) and interferon-γ (IFN-γ) was evaluated. The co-immunization caused a significant (P < .05) increase in the serum levels of IgG1 and IgG2a. The co-immunized mice splenocytes exhibited significantly enhanced IL-4 (6.6-fold) and IFN-γ (19-fold) production. Also, their lymphocytes exhibited higher proliferation rate (3-fold) and granzyme B production (6.5-fold) in comparison with the control. The prophylactic co-immunization significantly decreased the breast tumors' volume (78%) and increased the tumor-bearing mice survival time (37.5%) in comparison with the control. Taking together, prophylactic co-immunization with these multiepitope DNA and peptide cancer vaccines can activate the immune system against breast cancer. However, further experiments are needed to evaluate their efficacy from different angles.