Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.

The cell-surface receptor tyrosine kinase c-mesenchymal-epithelial transition factor (c-Met) is overexpressed in a wide range of solid tumors, making it an appropriate target antigen for the development of anticancer therapeutics. Various antitumor c-Met-targeting therapies (including monoclonal antibodies [mAbs] and tyrosine kinases) have been developed for the treatment of c-Met-overexpressing tumors, most of which have so far failed to enter the clinic because of their efficacy and complications. Antibody-drug conjugates (ADCs), a new emerging class of cancer therapeutic agents that harness the target specificity of mAbs to deliver highly potent small molecules to the tumor with the minimal damage to normal cells, could be an attractive therapeutic approach to circumvent these limitations in patients with c-Met-overexpressing tumors. Of great note, there are currently nine c-Met-targeting ADCs being examined in different phases of clinical studies as well as eight preclinical studies for treating various solid tumors. The purpose of this study is to present a broad overview of clinical- and preclinical-stage c-Met-targeting ADCs.

Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer.

Antibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity of a monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules to targeted cancer cells, leading to an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after the approval and tremendous success of trastuzumab emtansine and trastuzumab deruxtecan, representing a turning point in both HER2-positive breast cancer treatment and ADC technology. Additionally and importantly, a total of 29 ADC candidates are now being investigated in different stages of clinical development for the treatment of HER2-positive breast cancer. The purpose of this review is to provide an insight into the ADC field in cancer treatment and present a comprehensive overview of ADCs approved or under clinical investigation for the treatment of HER2-positive breast cancer.

Mini Bioreactor Can Support In Vitro Spermatogenesis of Mouse Testicular Tissue.

Objective: It was in the early 20th century when the quest for in vitro spermatogenesis started. In vitro spermatogenesis is critical for male cancer patients undergoing gonadotoxic treatment. Dynamic culture system creates in vivo-like conditions. In this study, it was intended to evaluate the progression of spermatogenesis after testicular tissue culture in mini-perfusion bioreactor. Materials and Methods: In this experimental study, 12 six-day postpartum neonatal mouse testes were removed and fragmented, placed on an agarose gel in parallel to bioreactor culture, and incubated for 8 weeks. Histological, molecular and immunohistochemical evaluations were carried out after 8 weeks. Results: Histological analysis suggested successful maintenance of spermatogenesis in tissues grown in the bioreactor but not on agarose gel, possibly because the central region did not receive sufficient oxygen and nutrients, which led to necrotic or degenerative changes. Molecular analysis indicated that Plzf, Tekt1 and Tnp1 were expressed and that their expression did not differ significantly between the bioreactor and agarose gel. Immunohistochemical evaluation of testis fragments showed that PLZF, SCP3 and ACRBP proteins were expressed in spermatogonial cells, spermatocytes and spermatozoa. PLZF expression after 8 weeks was significantly lower (P<0.05) in tissues incubated on agarose gel than in the bioreactor, but there was no significant difference between SCP3 and ACRBP expression among the bioreactor and agarose gel culture systems. Conclusion: This three-dimensional (3D) dynamic culture system can provide somewhat similar conditions to the physiological environment of the testis. Our findings suggest that the perfusion bioreactor supports induction of spermatogenesis for generation of haploid cells. Further studies will be needed to address the fertility of the sperm generated in the bioreactor system..

Development of a Novel Electroactive Cardiac Patch Based on Carbon Nanofibers and Gelatin Encouraging Vascularization.

Tissue engineering makes it possible to fabricate scaffolds that can help the function of defective tissues or even the most complex organs such as the heart. Carbon nanofibers (CNFs), because of their high mechanical strength and electrical properties, can improve the functional coupling of cardiomyocytes and their electrophysiological properties. In this study, electroactive CNF/gelatin (Gel) nanofibrous cardiac patches were prepared by an electrospinning method. Scanning electron microscope (SEM) evaluation of prepared scaffolds showed randomly oriented nanofibers. The electrical conductivity of the CNF/Gel scaffolds was assessed by a four-probe device and was in the semiconducting range (~ 10-5 S/m). The result of an MTT assay confirmed the excellent biocompatibility of electroactive CNF/Gel scaffolds. Also, CNF-containing scaffolds supported cardiomyocyte adhesion and increased expression of the cardiac genes including TrpT-2, Actn4, and Conx43 compared with the non-conductive counterpart. Our findings also confirmed the angiogenic potential of CNF/Gel scaffolds as compatible and electroactive platforms for cardiac tissue engineering.

Prevalence of Apical Periodontitis in Different Communities: A Meta-Analysis.

Introduction: The aim of this study was to perform a meta-analysis on the prevalence of apical periodontitis (AP) in different communities to obtain accurate data on its prevalence. Methods and Materials: The prevalence of AP in different communities based on the number of individuals, teeth and root-filled teeth was searched using electronic databases of ISI Web of Knowledge, PubMed, Scopus and also ProQuest and Springer. The Metaprop meta-analysis was done using the software R version 3.3.0 with Meta package. The Logit transformation method and random-effects model were used to calculate the pooled prevalence. Heterogeneity was tested by the Q-test (P<0.1 represented statistical significance), I2 statistics (25%, 50% and 75% represented low, medium and high heterogeneity, respectively) and 2τ (2τ was calculated by DerSimonian-Laird estimator method). Results: A total of 77 studies were identified to qualify for inclusion into this meta-analysis. The prevalence of AP based on the number of individuals, teeth and root-filled teeth with the pooled prevalence was 0.519, 0.0498 and 0.3828, respectively. Conclusions: The results of the present study can be helpful for policy makers to monitor the dental public health demographically and compare it to other communities; they may be able find the strengths and drawbacks of their oral and dental health program.