Search

Matrix stiffening is ubiquitous in solid tumors and can direct epithelial-mesenchymal transition (EMT) and cancer cell migration. Stiffened niche can even cause poorly invasive oral squamous cell carcinoma (OSCC) cell lines to acquire a less adherent, more migratory phenotype, but mechanisms and durability of this acquired "mechanical memory" are unclear. Here, we observed that contractility and its downstream signals could underlie memory acquisition; invasive SSC25 cells overexpress myosin II (vs. noninvasive Cal27 cells) consistent with OSCC. However, prolonged exposure of Cal27 cells to a stiff niche or contractile agonists up-regulated myosin and EMT markers and enabled them to migrate as fast as SCC25 cells, which persisted even when the niche softened and indicated "memory" of their prior niche. Stiffness-mediated mesenchymal phenotype acquisition required AKT signaling and was also observed in patient samples, whereas phenotype recall on soft substrates required focal adhesion kinase (FAK) activity. Phenotype durability was further observed in transcriptomic differences between preconditioned Cal27 cells cultured without or with FAK or AKT antagonists, and such transcriptional differences corresponded to discrepant patient outcomes. These data suggest that mechanical memory, mediated by contractility via distinct kinase signaling, may be necessary for OSCC to disseminate.

Background: Imidazolium salts (IS), ionic derivatives of neutral imidazoles, have properties that can be adjusted by structural modifications to their cations and anions, which makes this particular class of compounds a promising option for developing biologically active compounds. The anti‐tumor effects of the IS 1‐n‐butyl‐3‐methylimidazolium chloride (C4MImCl), 1‐n‐decyl‐3‐methylimidazolium chloride (C10MImCl), 1‐n‐hexadecyl‐3‐methylimidazolium chloride (C16MImCl), 1‐n‐hexadecyl‐2,3‐dimethylimidazolium chloride (C16M2ImCl), 1‐n‐octadecyl‐3‐methylimidazolium chloride (C18MImCl), 1‐n‐hexadecyl‐3‐methylimidazolium methanesulfonate (C16MImMeS), and 1‐n‐hexadecyl‐2,3‐ dimethylimidazolium methanesulfonate (C16M2ImMeS) on oral squamous cell carcinoma (OSCC) have been studied here. Methods: Oral squamous cell carcinoma cells (CAL27) were incubated with increasing IS doses and then submitted to proliferation (2D), cell death (2D) and spheroid assay (3D). Results: The IS anti‐tumor effect was dependent on both its N‐alkyl chain length and anion, whereby C16MImCl proved to be more effective in combination for inhibiting cell proliferation and cell‐cell adhesion, outperforming the methylated C16M2ImCl derivative and, most importantly, the gold standard—cisplatin. In addition, C16MImCl had little effect on keratinocytes and more pronounced effects on more aggressive tumor cells. It also exhibited similar effects on inducing cell death when compared to Cisplatin. This compound spread to a greater area of the tumor sphere and produced an enhanced number of apoptotic and necrotic cells in the tumor cell line, demonstrating only a small rise in the healthy cells. Conclusion: These data indicate that the effect of C16MlmCl on OSCC is promising, as it is selective for cancer cells. [ABSTRACT FROM AUTHOR]

Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Despite the enhancing effects of hyaluronidase (HYAL) over duration of anesthesia, this enzyme could cause adverse effects when injected concomitantly with local anesthetics in dental blocks.Objective: This study aimed to assess the tissue alterations caused by a local anesthetic protocol consisting of a late HYAL injection and confirm its functional effectiveness.Materials and Methods: The protocol efficacy was proved by evaluating sensory and motor functions in rats. The sciatic nerve was blocked with 2% lidocaine (LID) with epinephrine (n = 25). Thirty minutes later, 75 TRU/ml HYAL was injected into the same site (experimental group, LID/HYAL). One week later, this protocol was repeated in the contralateral hindlimb, injecting only HYAL's vehicle (control group, LID/vehicle [LID/V]). To observe the integrity of the local tissues, histological specimens were obtained 1, 24, 48, and 72 h after treatment with LID/HYAL or LID/V (n = 16 each) and stained with hematoxylin/eosin and picrosirius red.Results: Local inflammation was similar in both groups. The integrity of the nerve fibers was preserved, in spite of some inflammation-associated injuries in the surrounding tissues. The reversible tissue disorganization caused by HYAL, probably facilitated the diffusion of the residual anesthetic to the nerve, resulting in a prolonged anesthetic effect (P < 0.05).Conclusions: No irreversible morphological alterations are caused by the administration of HYAL prior the end of the LID-induced block. Moreover, this protocol prolongs LID's anesthetic effect. [ABSTRACT FROM AUTHOR]

Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome. [ABSTRACT FROM AUTHOR]