Harnessing the capacity of phytochemicals to enhance immune checkpoint inhibitor therapy of cancers: A focus on brain malignancies.

Brain cancers, particularly glioblastoma multiforme (GBM), are challenging health issues with frequent unmet aspects. Today, discovering safe and effective therapeutic modalities for brain tumors is among the top research interests. Immunotherapy is an emerging area of investigation in cancer treatment. Since immune checkpoints play fundamental roles in repressing anti-cancer immunity, diverse immune checkpoint inhibitors (ICIs) have been developed, and some monoclonal antibodies have been approved clinically for particular cancers; nevertheless, there are significant concerns regarding their efficacy and safety in brain tumors. Among the various tools to modify the immune checkpoints, phytochemicals show good effectiveness and excellent safety, making them suitable candidates for developing better ICIs. Phytochemicals regulate multiple immunological checkpoint-related signaling pathways in cancer biology; however, their efficacy for clinical cancer immunotherapy remains to be established. Here, we discussed the involvement of immune checkpoints in cancer pathology and summarized recent advancements in applying phytochemicals in modulating immune checkpoints in brain tumors to highlight the state-of-the-art and give constructive prospects for future research.

Application of RNA-based therapeutics in glioma: A review.

Despite the extensive advancements made in the field of cancer therapy, the outlook of individuals suffering from glioblastoma multiforme remains highly detrimental. The absence of specific treatments for cancerous cells significantly hinders the effectiveness of conventional anticancer techniques. Multiple research studies have demonstrated that the suppression of specific genes or the augmentation of therapeutic proteins through RNA-based therapeutics may represent a valuable approach when combined with chemotherapy or immunotherapy. In recent years, there has been a significant increase in the application of RNA therapeutics in conjunction with chemotherapy and immunotherapy. This emerging field has become a prominent area of research for advancing various types of cancer treatments. The present investigation provides an in-depth overview of the classification and application of RNA therapy, focusing on the mechanisms of RNA antitumor treatment and the current status of clinical studies on RNA drugs.

Advances in liposome-based delivery of RNA therapeutics for cancer treatment.

Liposomal drug delivery systems stand as versatile therapeutic platforms for precisely targeting related elements in cancerous tissues owing to their intrinsic passive and acquired active targeting capabilities and exceptional compatibility with physiologic environments. When the capacity of liposomes as nanocarriers is combined with the revolutionary potential of RNA therapies in affecting undruggable targets, the outcome would be promising drug candidates as game-changers in the cancer treatment arena. However, optimizing liposome composition, physicochemical properties, and surface chemistry is paramount to maximizing their pharmacokinetic and pharmacodynamic attributes. This review highlighted the potential of liposomes as nanovehicles for RNA therapeutics through a literature review and looked at the most recent preclinical and clinical advancements in utilizing liposomal RNA therapeutics for cancer management. Notably, the discovery of novel targets, advancements in liposome engineering, and organizing well-planned clinical trials would help uncover the incredible potential of these nanotherapeutics in cancer patients.

Modulation of the ubiquitin-proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors.

Regarding the multimechanistic nature of cancers, current chemo- or radiotherapies often fail to eradicate disease pathology, and frequent relapses or resistance to therapies occur. Brain malignancies, particularly glioblastomas, are difficult-to-treat cancers due to their highly malignant and multidimensional biology. Unfortunately, patients suffering from malignant tumors often experience poor prognoses and short survival periods. Thus far, significant efforts have been conducted to discover novel and more effective modalities. To that end, modulation of the ubiquitin-proteasome system (UPS) has attracted tremendous interest since it affects the homeostasis of proteins critically engaged in various cell functions, for example, cell metabolism, survival, proliferation, and differentiation. With their safe and multimodal actions, phytochemicals are among the promising therapeutic tools capable of turning the operation of various UPS elements. The present review, along with an updated outline of the role of UPS dysregulation in multiple cancers, provided a detailed discussion on the impact of phytochemicals on the UPS function in malignancies, especially brain tumors.

Aptamers against cancer drug resistance: Small fighters switching tactics in the face of defeat.

Discovering novel cancer therapies has attracted extreme interest in the last decade. In this regard, multidrug resistance (MDR) to chemotherapies is a key challenge in cancer treatment. Cancerous cells are growingly become resistant to existing chemotherapeutics by employing diverse mechanisms, highlighting the significance of discovering approaches to overcome MDR. One promising strategy is utilizing aptamers as unique tools to target elements or signaling pathways incorporated in resistance mechanisms, or develop actively targeted drug delivery systems or chimeras enabling the precise delivery of novel agents to inhibit the conventionally undruggable resistance elements. Furthermore, due to their advantages over their proteinaceous counterparts, particularly antibodies, including improved targeting action, enhanced thermal stability, easier production, and superior tumor penetration, aptamers are emerging and have frequently been considered for developing cancer therapeutics. Here, we highlighted significant chemoresistance pathways in cancer and discussed the use of aptamers as prospective tools to surmount cancer MDR.

Recent advances in glioblastoma multiforme therapy: A focus on autophagy regulation.

Despite conventional treatment options including chemoradiation, patients with the most aggressive primary brain tumor, glioblastoma multiforme (GBM), experience an average survival time of less than 15 months. Regarding the malignant nature of GBM, extensive research and discovery of novel treatments are urgently required to improve the patients' prognosis. Autophagy, a crucial physiological pathway for the degradation and recycling of cell components, is one of the exciting targets of GBM studies. Interventions aimed at autophagy activation or inhibition have been explored as potential GBM therapeutics. This review, which delves into therapeutic techniques to block or activate autophagy in preclinical and clinical research, aims to expand our understanding of available therapies battling GBM.

Thymol has anticancer effects in U-87 human malignant glioblastoma cells.

BACKGROUND: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87). METHODS AND RESULTS: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 µM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone. CONCLUSIONS: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells.

Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.

Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study.

BACKGROUND: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report. METHODS: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations. RESULTS: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals. CONCLUSION: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease.

The Effect of Intravitreal Bevacizumab on Central Serous Chorioretinopathy.

The aim of this study was to investigate the efficacy of Intravitreal Injection of Bevacizumab (IVB) in patients with Central Serous Chorioretinopathy (CSC) compared to the control group, after four months of injection. In this study, 30 eyes of 30 patients with CSC, who were in the age range of 23 to 50 years old (70% male subject) were included. Eligible patients were randomly allocated to the intervention (n = 15) and control groups (n = 15). Patients in the intervention group received a single dose injection of bevacizumab (1.25 mg in 0.05 mL), while patients in the control group were followed-up during the same time interval, without any medical interventions. Corrected Distance Visual Acuity (CDVA) and Central Macular Thickness (CMT) were evaluated as the primary outcome measures at the four-month follow-up. There was no statistically significant difference between the intervention and control groups regarding their baseline characteristics. Corrected Distance Visual Acuity was improved significantly in the intervention group (P < 0.001), while this improvement was not observed in the control group. Furthermore, greater improvement of CDVA was detected in the IVB group compared to the patients without injection (P = 0.018). The CMT findings were in line with CDVA changes in both groups, revealing a significant reduction of CMT only in the intervention group (P < 0.001). Also, thinner central retina was found in the intervention group compared to the comparison group, at the four-month follow-up (P < 0.001). Based on the findings, bevacizumab could be effective for improvement of both anatomical and functional outcomes in patients with CSC.

Short-Term Results of Sutureless Scleral Tunnel Trabeculectomy Using Adjunctive Topical Bevacizumab.

This study was performed to assess the short-term effect of sutureless scleral tunnel trabeculectomy procedure with and without topical bevacizumab. Thirty patients with Primary Open-Angle Glaucoma (POAG) were enrolled and randomly divided to two groups. Patients in the first group (15 patients) underwent sutureless trabeculectomy without topical bevacizumab and patients in the second group (15 patients) underwent sutureless trabeculectomy with 1.25 mg of topical bevacizumab. Intraocular Pressure (IOP) of both groups was measured by an expert ophthalmologist, without awareness of the patient's study group before the operation and six months post-operatively. Out of 30 patients in this study, six females (40%) and nine males (60%) underwent the sutureless trabeculectomy procedure (group A) as well as seven females (46.7%) and eight males (53.3%) underwent sutureless trabeculectomy with topical bevacizumab (group B). The mean age of the patients was not significantly different between the two groups (P = 0.91). A statistically significant difference in time variation of IOP was found between the two groups (P < 0.001). Mean IOP was 18.4 ± 4.35 mmHg in the sutureless group without bevacizumab and 11.73 ± 2.12 mmHg in the sutureless group with bevacizumab, six months post-surgically. No statistical significant differences were found in the baseline IOP between the two groups (P = 0.28). However, IOP changed significantly in group A and B from baseline to six months post-operatively (P = 0.004 and P < 0.001 respectively). According to the current findings, the sutureless trabeculectomy procedure is an effective surgical method for reduction of IOP. Addition of a single dose of 1.25 mg topical bevacizumab was more effective in reduction of IOP compared to sutureless trabeculectomy alone.