Advances in personalized radiotherapy.

Radiotherapy is a mainstay of cancer treatment. The clinical response to radiotherapy is heterogeneous, from a complete response to early progression. Recent studies have explored the importance of patient characteristics in response to radiotherapy. In this editorial, we invite contributions for a BMC Cancer collection of articles titled 'Advances in personalized radiotherapy' towards the improvement of treatment response.

A new approach to prevent radiation-induced xerostomia using intraglandular injection of mitochondria-boosting agents.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

The genetic landscape and possible therapeutics of neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. The most common tumors associated with NF2 are bilateral vestibular schwannoma, meningioma, and ependymoma. The clinical manifestations of NF2 depend on the site of involvement. Vestibular schwannoma can present with hearing loss, dizziness, and tinnitus, while spinal tumor leads to debilitating pain, muscle weakness, or paresthesias. Clinical diagnosis of NF2 is based on the Manchester criteria, which have been updated in the last decade. NF2 is caused by loss-of-function mutations in the NF2 gene on chromosome 22, leading the merlin protein to malfunction. Over half of NF2 patients have de novo mutations, and half of this group are mosaic. NF2 can be managed by surgery, stereotactic radiosurgery, monoclonal antibody bevacizumab, and close observation. However, the nature of multiple tumors and the necessity of multiple surgeries over the lifetime, inoperable tumors like meningiomatosis with infiltration of the sinus or in the area of the lower cranial nerves, the complications caused by the operation, the malignancies induced by radiotherapy, and inefficiency of cytotoxic chemotherapy due to the benign nature of NF-related tumors have led a march toward exploring targeted therapies. Recent advances in genetics and molecular biology have allowed identifying and targeting of underlying pathways in the pathogenesis of NF2. In this review, we explain the clinicopathological characteristics of NF2, its genetic and molecular background, and the current knowledge and challenges of implementing genetics to develop efficient therapies.

Intra-prostatic gold fiducial marker insertion for image-guided radiotherapy (IGRT): five-year experience on 795 patients.

INTRODUCTION: Prostate cancer is the second most commonly diagnosed cancer in males. The use of intra-prostatic fiducial markers (FM) for image-guided radiotherapy (IGRT) has become widespread due to their accuracy, relatively safe use, low cost, and reproducibility. FM provides a tool to monitor prostate position and volume changes. Many studies reported low to moderate rates of complications following FM implantation. In the current study, we present our five years' experience regarding the insertion technique, technical success, and rates of complication and migration of intraprostatic insertion of FM gold marker. METHODS: From January 2018 to January 2023, 795 patients with prostate cancer candidate for IGRT (with or without a history of radical prostatectomy) enrolled in this study. We used three fiducial markers (3*0.6 mm) inserted through an 18-gauge Chiba needle under transrectal ultrasonography (TRUS) guidance. The patients were observed for complications up to seven days after the procedure. Besides, the rate of marker migration was recorded. RESULTS: All procedures were completed successfully, and all patients tolerated the procedure well with minimal discomfort. The rate of sepsis after the procedure was 1%, and transient urinary obstruction was 1.6%. Only two patients experienced marker migration shortly after insertion, and no fiducial migration was reported throughout radiotherapy. No other major complication was recorded. DISCUSSION: TRUS-guided intraprostatic FM implantation is technically feasible, safe, and well-tolerated in most patients. The FM migration can seldom occur, with negligible effects. This study can provide convincing evidence that TRUS-guided intra-prostatic FM insertion is an appropriate choice for IGRT.

Clinical Characteristics and Outcomes of COVID-19 in 1294 New Cancer Patients: Single-Center, Prospective Cohort Study from Iran.

OBJECTIVE: To determine the clinical characteristics and outcomes of COVID-19 in a large cohort of new cancer patients referred to an oncology clinic in the north of Iran. METHODS: During the 20-month COVID-19 pandemic, new cancer patients were followed-up. Demographic, pathologic, and clinical variables were collected for each patient. COVID-19 was confirmed based on a positive polymerase chain reaction test. Analyses were performed using the STATA version 14.0 at a significance level of 0.05. RESULTS: In this study, 1294 new cancer patients were followed for 24 months (mean age: 58.7 years [range 10-95]). During the study period, COVID-19 was diagnosed in 9.4% of the patients with hospitalization rate of 3.4%, an ICU admission rate of 0.7%, and COVID-19 mortality rate of 4.9%. Hematological malignancies (ORU= 2.6, CI95% 1.28-5.34), receiving palliative treatments (ORA=3.03, CI95% 1.6-5.45) and receiving radiotherapy (ORA=2.07, 1.17-3.65) were the most common predictive factors of COVID infection in cancer patients. Also, the COVID mortality was higher in brain cancer patients (p = 0.07), metastatic disease (p = 0.01) and patients receiving palliative treatments (p = 0.02). CONCLUSION: In patients suffering from cancer, COVID-19 infection can be predicted by cancer type, palliative care, and radiotherapy in cancer patients. Furthermore, brain cancers, metastasis, and palliative care were all associated with COVID-19-related mortality.

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran, Iran.

AIM: To provide recommendations for the management of patients with cancer in the COVID-19 era. BACKGROUND: The current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities. METHODS: In this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran. RESULTS: We recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic. CONCLUSIONS: Our recommendation provides a guide for oncology centers of developing countries for better management of cancer.

Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity.

BACKGROUND: Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated. METHODS: The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays. RESULTS: TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells. CONCLUSION: The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.

Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation.

This review article explores the dynamic field of radiopharmaceuticals, where innovative developments arise from combining radioisotopes and pharmaceuticals, opening up exciting therapeutic possibilities. The in-depth exploration covers targeted drug delivery, delving into passive targeting through enhanced permeability and retention, as well as active targeting using ligand-receptor strategies. The article also discusses stimulus-responsive release systems, which orchestrate controlled release, enhancing precision and therapeutic effectiveness. A significant focus is placed on the crucial role of radiopharmaceuticals in medical imaging and theranostics, highlighting their contribution to diagnostic accuracy and image-guided curative interventions. The review emphasizes safety considerations and strategies for mitigating side effects, providing valuable insights into addressing challenges and achieving precise drug delivery. Looking ahead, the article discusses nanoparticle formulations as cutting-edge innovations in next-generation radiopharmaceuticals, showcasing their potential applications. Real-world examples are presented through case studies, including the use of radiolabelled antibodies for solid tumors, peptide receptor radionuclide therapy for neuroendocrine tumors, and the intricate management of bone metastases. The concluding perspective envisions the future trajectory of radiopharmaceuticals, anticipating a harmonious integration of precision medicine and artificial intelligence. This vision foresees an era where therapeutic precision aligns seamlessly with scientific advancements, ushering in a new epoch marked by the fusion of therapeutic resonance and visionary progress.

Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss.

Sensorineural hearing loss (SNHL), often stemming from reactive oxygen species (ROS) generation due to various factors such as ototoxic drugs, acoustic trauma, and aging, remains a significant health concern. Oxidative stress-induced damage to the sensory cells of the inner ear, particularly the non-regenerating hair cells, is a critical pathologic mechanism leading to SNHL. Despite the proven efficacy of antioxidants in mitigating oxidative stress, their clinical application for otoprotection is hindered by the limitations of conventional drug delivery methods. This review highlights the challenges associated with systemic and intratympanic administration of antioxidants, including the blood-labyrinthine barrier, restricted permeability of the round window membrane, and inadequate blood flow to the inner ear. To overcome these hurdles, the application of nanoparticles as a delivery platform for antioxidants emerges as a promising solution. Nanocarriers facilitate indirect drug delivery to the cochlea through the round and oval window membrane, optimising drug absorption while reducing dosage, Eustachian tube clearance, and associated side effects. Furthermore, the development of nanoparticles carrying antioxidants tailored to the intracochlear environment holds immense potential. This literature research aimed to critically examine the root causes of SNHL and ROS overproduction in the inner ear, offering insights into the application of nanoparticle-based drug delivery systems for safeguarding sensorineural hair cells. By focusing on the intricate interplay between oxidative stress and hearing loss, this research aims to contribute to the advancement of innovative therapeutic strategies for the prevention of SNHL.

Improvement of spatial learning and memory deficits by intranasal administration of human olfactory ecto-mesenchymal stem cells in an Alzheimer's disease rat model.

Mesenchymal stem cells therapy provides a new perspective of therapeutic approaches in the treatment of neurodegenerative diseases. The present study aimed to investigate the effects of intranasally transplanted human "olfactory ecto-mesenchymal stem cells" (OE-MSCs) in Alzheimer's disease (AD) rats. In this study, we isolated OE-MSCs from human olfactory lamina propria and phenotypically characterized them using immunocytochemistry and flow cytometry. The undifferentiated OE-MSCs were transplanted either by intranasal (IN) or intrahippocampal (IH) injection to rat models of AD, which were induced by injecting amyloid-beta (Aß) intrahippocampally. Behavioral, histological, and molecular assessments were performed after a three-month recovery period. Based on the results, intranasal administration of OE-MSCs significantly reduced Aß accumulation and neuronal loss, improved learning and memory impairments, and increased levels of BDNF (brain-derived neurotrophic factor) and NMDAR (N-methyl-D-Aspartate receptors) in the AD rat model. These changes were more significant in animals who received OE-MSCs by intranasal injection. The results of this study suggest that OE-MSCs have the potential to enhance cognitive function in AD, possibly mediated by BDNF and the NMDA receptors.

Application of artificial intelligence (AI) to control COVID-19 pandemic: Current status and future prospects.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the everyday livelihood of people has been monumental and unparalleled. Although the pandemic has vastly affected the global healthcare system, it has also been a platform to promote and develop pioneering applications based on autonomic artificial intelligence (AI) technology with therapeutic significance in combating the pandemic. Artificial intelligence has successfully demonstrated that it can reduce the probability of human-to-human infectivity of the virus through evaluation, analysis, and triangulation of existing data on the infectivity and spread of the virus. This review talks about the applications and significance of modern robotic and automated systems that may assist in spreading a pandemic. In addition, this study discusses intelligent wearable devices and how they could be helpful throughout the COVID-19 pandemic.

A Critical Review on the Role of Probiotics in Lung Cancer Biology and Prognosis.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

A Critical Review on the Long-Term COVID-19 Impacts on Patients With Diabetes.

BACKGROUND: The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches. METHODS: Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023. RESULTS: COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients. CONCLUSIONS: Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

Possible roles of phytochemicals with bioactive properties in the prevention of and recovery from COVID-19.

Introduction: There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/beverages people consumed and the risk reduction of contracting COVID-19 and the recovery from COVID-19. Methods: We developed an online survey that asked the participants whether they contracted COVID-19, their symptoms, time to recover, and their frequency of eating various types of foods/beverages. The survey was developed in 10 different languages. Results: The participants who did not contract COVID-19 consumed vegetables, herbs/spices, and fermented foods/beverages significantly more than the participants who contracted COVID-19. Among the six countries (India/Iran/Italy/Japan/Russia/Spain) with over 100 participants and high correspondence between the location of the participants and the language of the survey, in India and Japan the people who contracted COVID-19 showed significantly shorter recovery time, and greater daily intake of vegetables, herbs/spices, and fermented foods/beverages was associated with faster recovery. Conclusions: Our results suggest that phytochemical compounds included in the vegetables may have contributed in not only preventing contraction of COVID-19, but also accelerating their recovery.

The Metastatic Spread of Breast Cancer Accelerates during Sleep: How the Study Design can Affect the Results.

Metastasis is the most common event that determines survival in patients with breast cancer. The benefits of appropriate sleep in enhancing cancer patients' prognosis have been demonstrated. Likewise, emerging evidence has noted the positive impacts of regular circadian rhythm on cancer survival. Proper sleep and regular circadian rhythm can help to improve the cancer prognosis by enhancing the immune system. Besides, circadian rhythm disruption can assist cancer progression by promoting systemic inflammation. However, a recent study by Diamantopoulou et al. titled "The Metastatic Spread of Breast Cancer Accelerates during Sleep" demonstrated that sleep can aggravate breast cancer metastasis. This article outlines how the study design can affect this controversy.

Mitochondrial Metabolism: A New Dimension of Personalized Oncology.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells' biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironments, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The tumors' responses to anticancer treatments vary, ranging from a complete response to even cancer progression during treatment. Therefore, personalized cancer treatment is of crucial importance. So far, personalized cancer treatment has been based on genomic analysis. Evidence shows that tumors with high mitochondrial content are more resistant to treatment. This paper illustrates how mitochondrial metabolism can participate in cancer resistance to chemotherapy, immunotherapy, and radiotherapy. Pretreatment evaluation of mitochondrial metabolism can provide additional information to genomic analysis and can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

COVID-19 induced liver injury from a new perspective: Mitochondria.

Liver damage is a common sequela of COVID-19 (coronavirus disease 2019), worsening the clinical outcomes. However, the underlying mechanism of COVID-induced liver injury (CiLI) is still not determined. Given the crucial role of mitochondria in hepatocyte metabolism and the emerging evidence denoting SARS-CoV-2 can damage human cell mitochondria, in this mini-review, we hypothesized that CiLI happens following hepatocytes' mitochondrial dysfunction. To this end, we evaluated the histologic, pathophysiologic, transcriptomic, and clinical features of CiLI from the mitochondria' eye view. Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), the causative agent of COVID-19, can damage hepatocytes through direct cytopathic effects or indirectly after the profound inflammatory response. Upon entering the hepatocytes, the RNA and RNA transcripts of SARS-CoV-2 engages the mitochondria. This interaction can disrupt the mitochondrial electron transport chain. In other words, SARS-CoV-2 hijacks the hepatocytes' mitochondria to support its replication. In addition, this process can lead to an improper immune response against SARS-CoV-2. Besides, this review outlines how mitochondrial dysfunction can serve as a prelude to the COVID-associated cytokine storm. Thereafter, we indicate how the nexus between COVID-19 and mitochondria can fill the gap linking CiLI and its risk factors, including old age, male sex, and comorbidities. In conclusion, this concept stresses the importance of mitochondrial metabolism in hepatocyte damage in the context of COVID-19. It notes that boosting mitochondria biogenesis can possibly serve as a prophylactic and therapeutic approach for CiLI. Further studies can reveal this notion.

Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity.

INTRODUCTION: Radiotherapy is a mainstay of cancer treatment. Clinical studies revealed a heterogenous response to radiotherapy, from a complete response to even disease progression. To that end, finding the relative prognostic factors of disease outcomes and predictive factors of treatment efficacy and toxicity is essential. It has been demonstrated that radiation response depends on DNA damage response, cell cycle phase, oxygen concentration, and growth rate. Emerging evidence suggests that altered mitochondrial metabolism is associated with radioresistance. METHODS: This article provides a comprehensive evaluation of the role of mitochondria in radiotherapy efficacy and toxicity. In addition, it demonstrates how mitochondria might be involved in the famous 6Rs of radiobiology. RESULTS: In terms of this idea, decreasing the mitochondrial metabolism of cancer cells may increase radiation response, and enhancing the mitochondrial metabolism of normal cells may reduce radiation toxicity. Enhancing the normal cells (including immune cells) mitochondrial metabolism can potentially improve the tumor response by enhancing immune reactivation. Future studies are invited to examine the impacts of mitochondrial metabolism on radiation efficacy and toxicity. Improving radiotherapy response with diminishing cancer cells' mitochondrial metabolism, and reducing radiotherapy toxicity with enhancing normal cells' mitochondrial metabolism.

A comparison of two chemotherapy regimens in advanced, recurrent, or metastatic salivary gland carcinoma.

Background: The efficacy of chemotherapy in locally advanced, recurrent, and metastatic salivary gland carcinomas (LA-R/M SGCs) is still undefined. We aimed to compare the efficacy of two chemotherapy regimens in LA-R/M SGC. Materials and Methods: This prospective study compared paclitaxel (Taxol) plus carboplatin (TC) versus cyclophosphamide, doxorubicin, plus cisplatin (CAP) regimen in terms of overall response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Results: Between October 2011 and April 2019, 48 patients with LA-R/M SGCs were recruited. The ORRs of first-line TC and CAP regimens were 54.2% and 36.3%, respectively (P = 0.57). The ORRs in recurrent and de novo metastatic patients were 50.0% and 37.5% for TC and CAP, respectively (P = 0.26). The median PFS of TC and CAP arms were 10.2 and 11.9 months, respectively (P = 0.91). In the subanalysis, patients with adenoid cystic carcinoma (ACC) had longer PFS in the TC arm (14.5 vs. 8.2 months, P = 0.03), irrespective of the tumor grade (low grade: 16.3 vs. 8.9 months, high grade: 11.7 vs. 4.5 months; P = 0.03). The median OS rates were 45.5 and 19.5 months for TC and CAP groups, respectively (P = 0.71). Conclusion: For patients with LA-R/M SGC, there was no significant difference between first-line TC and CAP in terms of ORR, PFS, and OS.

Ciliated, Mitochondria-Rich Postmitotic Cells are Immune-privileged, and Mimic Immunosuppressive Microenvironment of Tumor-Initiating Stem Cells: From Molecular Anatomy to Molecular Pathway.

Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading cause of death worldwide. Tumor-initiating stem cells (TiSCs) are a subset of the tumor population responsible for tumor resistance and relapse. Understanding the characteristics and shared features between tumor-initiating stem cells (TiSCs) and long-lived postmitotic cells may hold a key to better understanding the biology of cancer. Postmitotic cells have exited the cell cycle and are transitioned into a non-dividing and terminally differentiated state with a specialized function within a tissue. Conversely, a cancer cell with TiSC feature can divide and produce a variety of progenies, and is responsible for disease progression, tumor resistance to therapy and immune system and disease relapse. Surprisingly, our comprehensive evaluation of TiSCs suggests common features with long-lived post-mitotic cells. They are similar in structure (primary cilia, high mitochondrial content, and being protected by a barrier), metabolism (autophagy and senescence), and function (immunoescape and/or immune-privileged by a blood barrier). In-depth exploration showed how mitochondrial metabolism contributes to these shared features, including high energy demands arising from ciliary and microtubular functionality, increased metabolic activity, and movement. These findings can assist in decoding the remaining properties which offer insights into the biology of TiSCs, with potential implications for enhancing cancer treatment strategies and patient prognosis.