Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities.

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

Characterization of Rajath Bhasma and Evaluation of Its Toxicity in Zebrafish Embryos and Its Antimicrobial Activity.

In India, nanotechnology has been used in therapeutic applications for several millennia. One example of a traditional nanomedicine is Rajath Bhasma (als°Called calcined silver ash), which is used as an antimicrobial and for the treatment of various ailments and conditions such as memory loss, eye diseases, and dehydration. In this study, we aimed t°Characterize the physical composition and morphology of Rajath Bhasma and its suitability for use as a non-toxic antimicrobial agent. First, Rajath Bhasma was physically characterized via i) Fourier-transform infrared spectroscopy to analyze the surface functional groups, ii) scanning electron microscopy coupled with energydispersive X-ray spectroscopy to observe the morphology and elemental composition, and iii) X-ray diffraction to determine the crystalline phases. Thereafter, functional characterization was performed through toxicity screening using zebrafish embryos and through antimicrobial activity assessment against gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria. Rajath Bhasma was found to harbor alkene, hydroxyl, aldehyde, and amide functional groups originating from biological components on its surface. The main component of Rajath Bhasma is silver, with particle size of 170-210 nm, and existing in the form of spherical aggregates with pure crystalline silver structures. Furthermore, Rajath Bhasma did not exert toxic effects on zebrafish embryos at concentrations below 5 µg/ml and exhibited effective antimicrobial activity against both gram-positive and gram-negative bacteria. The present results indicate that Rajath Bhasma is a potentially effective antimicrobial agent without toxicity when used at concentrations below 5 µg/ml.

Fluorescence, turn-on detection of melamine based on its dual functions as fluorescence enhancer of DNA-AgNCs and Hg(II)-scavenger.

A new method has been developed for the simple, fluorescence, turn-on detection of melamine, which utilizes DNA-templated silver nanoclusters (DNA-AgNCs) as a key component. In the sensor, melamine exhibits the dual functions: one is to enhance the fluorescence signal of DNA-AgNCs by its specific interaction with thymine residues in DNA template, and the other is to prevent Hg(II)-induced fluorescence quenching of DNA-AgNCs via its strong coordination with Hg(II). These consequently enable the sensitive and selective detection of melamine. By exploiting such novel features of melamine, we significantly increased the fluorescence response up to 360%, compared to the previous counterpart that relies on DNA-AgNCs only, and successfully determined melamine down to ca. 49 nM, a value that is 400 times lower than the safety level of 20 µM set by the US Food and Drug Administration. In addition, it was confirmed that the proposed approach works fine even in the real milk samples without any additional pre-treatment steps.

The use of a 2-aminopurine-containing split G-quadruplex for sequence-specific DNA detection.

A simple, sequence-specific DNA detection method, utilizing a fluorescent 2-aminopurine (2-AP) nucleobase analogue-containing split G-quadruplex as the key detection component, is described. In the sensor, the 2-AP-containing G-quadruplex is split into two segments and linked to a target-specific overhang sequence. The separate G-quadruplex sequences form an active G-quadruplex structure only in the presence of a complementary target DNA, which leads to a significant increase in the intensity of fluorescence from the 2-AP fluorophore. This simple, one-step, homogenous assay was successfully employed to detect target DNA with a high selectivity. In addition, the practical applicability of the detection method was demonstrated by its use in analyzing target DNAs in human serum. To the best of our knowledge, this is the first time that an investigation was carried out in which a fluorescent nucleobase analogue was incorporated into a split G-quadruplex structure and this structure was utilized as the foundation for a specific DNA sensor.