Chemo-and Radiotherapy Research Articles

FBXO7 Confers Mesenchymal Properties and Chemoresistance in Glioblastoma by Controlling Rbfox2-Mediated Alternative Splicing.

Mesenchymal glioblastoma (GBM) is highly resistant to radio-and chemotherapy and correlates with worse survival outcomes in GBM patients; however, the underlying mechanism determining the mesenchymal phenotype remains largely unclear. Herein, it is revealed that FBXO7, a substrate-recognition component of the SCF complex implicated in the pathogenesis of Parkinson's disease, confers mesenchymal properties and chemoresistance in GBM by controlling Rbfox2-mediated alternative splicing. Specifically, FBXO7 ubiquitinates Rbfox2 Lys249 through K63-linked ubiquitin chains upon arginine dimethylation at Arg341 and Arg441 by PRMT5, leading to Rbfox2 stabilization. FBXO7 controls Rbfox2-mediated splicing of mesenchymal genes, including FoxM1, Mta1, and Postn. FBXO7-induced exon Va inclusion of FoxM1 promotes FoxM1 phosphorylation by MEK1 and nuclear translocation, thereby upregulates CD44, CD9, and ID1 levels, resulting in GBM stem cell self-renewal and mesenchymal transformation. Moreover, FBXO7 is stabilized by temozolomide, and FBXO7 depletion sensitizes tumor xenografts in mice to chemotherapy. The findings demonstrate that the FBXO7-Rbfox2 axis-mediated splicing contributes to mesenchymal transformation and tumorigenesis, and targeting FBXO7 represents a potential strategy for GBM treatment.

Chemotherapeutic Effects of Boswellic Acid Against Human Glioblastoma Multiform: A Comprehensive Review

Background: Glioblastoma multiform (GBM) is a malignant subgroup of gliomas. Due to the natural resistance of GBM cells to radio-and chemotherapy usually, recurrence occurs 6-9 months after diagnosis. Objective: This paper reviewed the beneficial effects of Boswellic acid (BA) in adjacent therapy for GBM, based on its possible molecular mechanisms. Methods: In this review paper, all papers indexed in scientific databases, including PubMed, Scopus, Embase, Google Scholar, and Elsevier were searched during 2000 - 2021 using apoptosis, Boswellic acid, cancer, glioblastoma multiform, inflammation, oxidative stress as keywords. Results: The most important compounds of BAs are alpha-boswellic acid, beta- boswellic acid, acetylbeta- boswellic acid, acetyl-alpha- boswellic acid, and 11-keto-beta- boswellic acid (KBA). Antiinflammation, reduction of skin irritation, anti-tumor, anti-cancer, anxiolytic, and anti-phlogistic are the main properties of BAs. Boswellic acid is recognized as a chemopreventive agent. Boswellic acid exerts its effects mainly via various mechanisms such as induction of apoptosis and cytotoxic effects on malignant cells, activation of caspases, up-regulation of genes expression with potential antiapoptotic and pro-survival properties, inhibition the signaling and activity pathway of nuclear factorkappa B (NF-κB) and enhancing poly (ADP)-ribose polymerase (PARP) cleavage. Boswellic acid inhibits the signaling pathway of 5 and 12-lipoxygenase (5, 12 LOX), and cyclooxygenase-2 (COX-2), which are considered triggers in the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Conclusion: Future clinical trials are needed to identify the interaction between Boswellic acid and the severity of GBM and to define the safe dose and effective duration of supplementation.

A case of primary multiple synchronous radiogenic cancer in clinical practice

There is an increase in the number of patients with secondary malignant neoplasms. In addition, in some subgroups after radical cancer treatment, the lifetime risk of developing secondary malignant neoplasms can be as high as 33 %. Secondary malignancies remain an important cause of death in patients who have received radical cancer treatment. The presented clinical case demonstrates the risk of developing primary multiple malignant neoplasms after radiation therapy and chemotherapy. A 39‑year-old patient with diffuse large B-cell non-Hodgkin lymphoma underwent definitive treatment including chemo-and radiotherapy. Ten years later, the patient developed the induced multiple malignant tumors: a malignant neoplasm of the heart — myofibrosarcoma of the right ventricle with invasion of the anterior wall of the right ventricle Stage IIIB G2T3N0M0, left breast cancer Stage IIIA T3N2M0. The choice of treatment tactics for this category of patients remains particularly difficult.

The Role of Hypoxia and Cancer Stem Cells in Development of Glioblastoma.

Glioblastoma multiform (GBM) is recognized as the most malignant brain tumor with a high level of hypoxia, containing a small population of glioblastoma stem like cells (GSCs). These GSCs have the capacity of self-renewal, proliferation, invasion and recapitulating the parent tumor, and are major causes of radio-and chemoresistance of GBM. Upregulated expression of hypoxia inducible factors (HIFs) in hypoxia fundamentally contributes to maintenance and progression of GSCs. Therefore, we thoroughly reviewed the currently acknowledged roles of hypoxia-associated GSCs in development of GBM. In detail, we recapitulated general features of GBM, especially GSC-related features, and delineated essential responses resulted from interactions between GSC and hypoxia, including hypoxia-induced signatures, genes and pathways, and hypoxia-regulated metabolic alterations. Five hypothesized GSC niches are discussed and integrated into one comprehensive concept: hypoxic peri-arteriolar niche of GSCs. Autophagy, another protective mechanism against chemotherapy, is also closely related to hypoxia and is a potential therapeutic target for GBM. In addition, potential causes of therapeutic resistance (chemo-, radio-, surgical-, immuno-), and chemotherapeutic agents which can improve the therapeutic effects of chemo-, radio-, or immunotherapy are introduced and discussed. At last, as a potential approach to reverse the hypoxic microenvironment in GBM, hyperbaric oxygen therapy (HBOT) might be an adjuvant therapy to chemo-and radiotherapy after surgery. In conclusion, we focus on demonstrating the important role of hypoxia on development of GBM, especially by affecting the function of GSCs. Important advantages have been made to understand the complicated responses induced by hypoxia in GBM. Further exploration of targeting hypoxia and GSCs can help to develop novel therapeutic strategies to improve the survival of GBM patients.

Sodium deoxyribonucleate effects on the status of cervical cancer patients after radiotherapy

Background. Apart from surgery and medications, radiation therapy is one of the main treatment methods for malignant tumors of the cervix. However, its use is associated with high incidence of urological complications. In addition, the need for long-term treatment, reduced level of patients’ quality of life promote the necessity to minimize the frequency of urological complications and justify search and study of the most adequate methods of their prevention.Aim. To evaluate the effect of radioprotector sodium deoxyribonucleate on clinical characteristics and quality of life of patients with cervical cancer after radiation treatment.Materials and methods. 80 patients with cervical cancer treated in A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncology Dispensary. Patients received chemoand radiotherapy with the 3D conformal radiotherapy method in combination with intracavity gamma therapy sources of high dose with subsequent application of radioprotector and without it.Results. On the 3rd visit it was found that in patients with cervical cancer using a radioprotector, reduced red blood cells and flat epithelium cells content in the urine sediment, it may be due to the reparative and cytoprotective sodium deoxyribonucleate properties. In the assessment of the life quality after combined therapy completion with radioprotector, 60 % of patients’ responses to the health assessment questions of the last week differed from the comparison group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not observed in cervical cancer patients during radiotherapy and subsequent observation period.Conclusion. Conformal external beam radiation therapy in combination with long-term intramuscular administration of a radioprotector has advantages compared to 3D conformal radiation therapy. This method reduces the severity of post-radiation side effects, increases time to development of hematological toxicity in the context of combination chemoradiotherapy, and reduces urothelial damage caused by chemoradiotherapy.

FA-HA-Amygdalin@Fe2O3 and/or γ-Rays Affecting SIRT1 Regulation of YAP/TAZ-p53 Signaling and Modulates Tumorigenicity of MDA-MB231 or MCF-7 Cancer Cells.

Breast cancer (BC) has a complex and heterogeneous etiology, and the emergence of resistance to conventional chemo-and radiotherapy results in unsatisfactory outcomes during BC treatment. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Hence, this study aimed to evaluate the newly fabricated pH-sensitive multifunctional FAHA- Amygdalin@Fe2O3 nano-core-shell composite (AF nanocomposite) and/or γ-radiation for effective localized BC therapy. The physicochemical properties of nanoparticles were examined, including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy. MCF-7 and MDA-MB-231 cells were treated with AF at the determined IC50 doses and/or exposed to γ-irradiation (RT) or were kept untreated as controls. The antitumor efficacy of AF was proposed via assessing anti-proliferative effects, cell cycle distribution, apoptosis, and determination of the oncogenic effectors. In a bio-relevant medium, AF nanoparticles demonstrated extended-release characteristics that were amenable to acidic pH and showed apparent selectivity towards BC cells. The bioassays revealed that the HA and FA-functionalized AF markedly hindered cancer cell growth and enhanced radiotherapy (RT) through inducing cell cycle arrest (pre-G1 and G2/M) and increasing apoptosis, as well as reducing the tumorigenicity of BCs by inhibiting Silent information regulation factor 1 (SIRT1) and restoring p53 expression, deactivating the Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling axis, and interfering with the tumor growth factor- β(TGF- β)/SMAD3 and HIF-1α/VEGF signaling hub while up-regulating SMAD7 protein expression. Collectively, the novel AF alone or prior RT abrogated BC tumorigenicity.

Silencing PARP-1 binding protein Inhibits Cell Migration and Invasion via Suppressing UBE2C in Nasopharyngeal Cancer Cells.

Nasopharyngeal carcinoma (NPC) is a malignancy with a 2 per 100000 incidence rate in the world. Overall survival (OS) of patients in stage I-II disease is around 80%, whereas OS of patients in stage III-IVB disease drops to 60%, implying the importance of diagnosis to reduce NPC mortality. However, more than 70% patients of NPC were diagnosed at advanced stages (stage III and IV) in clinics, and it definitely contributes to little substantial improvement in the 5-year survival rates although NPC is sensitive to radio-and chemotherapy. Hence, development of novel biomarkers and targetable genes in NPC is eagerly awaited. We had analyzed the dataset GSE12452 and found hundreds of genes trans-activated in NPC. Among them, this study focused on PARP-1 binding protein (PARPBP) whose overexpression was also validated in GSE13597 and GSE53819 datasets. Knockdown of PARPBP significantly reduced cell viability in NPC and also identified hundreds of differentially expressed genes including 377 downregulated and 518 upregulated genes in HONE-1 cells with stably knockdown PARPBP. Furthermore, PARPBP might promote cell migration and invasion in NPC through positive regulation of ubiquitin-conjugating enzyme 2C (UBE2C). The results demonstrate the aberrant expression of PARPBP in NPC, and imply its importance in nasopharyngeal carcinogenesis which further opens up the possibility of PARPBP as a novel diagnostic biomarker for NPC therapy.

Abstract 3774: The effect of CDK5 on mitochondrial function in Glioblastoma Multiforme (GBM)

Abstract Glioblastoma Multiforme (GBM) is the most common and aggressive form of brain tumors.Despite conventional therapies, average patient survival is less than two years. GBMrecurrence is in part due to self-renewing tumor initiating cells, often called glioma stemcells (GSCs), which are characterized by their proliferation and tumor formation capacity,as well as their metabolic features. Thus, mitochondrial function represents a potentiallink between cellular metabolism and differentiation state. Mitochondrial fission isindispensable for growing and dividing cells. Dynamin-related protein 1 (Drp1) is essentialfor this process. In particular, there is cumulative evidence that links Drp1 with severaltypes of cancers, including GBM. Regulation of Drp1 is mainly controlled by post-translational modifications (PTMs). Importantly, recent studies have shown CDK5-dependent phosphorylation at the activating site serine 616 of Drp1 enhancesmitochondrial fission. CDK5 plays a crucial role in the central nervous system as well as,in tumor progression. Therefore, our lab hypothesized that inhibition of CDK5 would targetmitochondrial function in order to decrease tumor growth and sensitize brain tumors toconventional therapies. Western blot analysis has shown that CDK5-dependentphosphorylation of Drp1 is present in GSCs and GBM cell lines but absent in non-stemtumor cells (NSTC) and astrocytes. Small-molecule CDK5 inhibitors or CDK5 knockdownthrough siRNA in GSCs and GBM cell lines decreased activating phosphorylation of Drp1,leading to elongation of mitochondria morphology and corresponding reductions in cellviability and cell proliferation. Additionally, CDK5 inhibition showed sensitization toionizing radiation (IR) in GSCs and GBM cells. Importantly, CDK5 inhibition or knockdowncombined with IR, showed increased levels of cleaved caspase-7 and cleaved PARPsuggesting a role for apoptosis in decreased cell proliferation and sensitization to IR.Interestingly, CDK5 inhibition also diminished mitochondrial oxidative phosphorylation.Overall, these findings highlight an important role for CDK5 in regulating mitochondrialfunction in GBM, and targeting CDK5 offers a novel strategy to sensitize tumors to chemo-and radiotherapies. Citation Format: Adina Brett-Morris, Jason Mears, Kristy Rochon. The effect of CDK5 on mitochondrial function in Glioblastoma Multiforme (GBM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3774.

Interdisciplinary approach to the management of patients with uterine cancer progression

Endometrial cancer is the most common gynecologic malignancy in Russia. Surgery and/or chemoand radiotherapy remain standard clinical approach. This review describes multidisciplinary approach as the state of the art in the disease management. We notice the importance of molecular assessment for driving the clinic decision and newly emerging medical treatments, such as immunotherapy and antiangiogenic tyrosine kinase inhibitors and immunotherapy combinations.

Changes in surgical principles as a result of modern, effective, perioperative treatments

Oncology has evolved to a great extent over the last quarter of century. The significant success is multifactorial, including primary and secondary prevention, the development of diagnostics, new methods of chemo-and radiotherapy, and the integration of basic research results into practice. From the point of view of surgery, the establishing and widespread practical application of the principles of preoperative oncotherapy played a major role in this development. Between 1997 and 2005, 44 patients with gastric cancer and 102 patients with borderline resectable or irresectable esophageal cancer received perioperative treatment at the Department of Surgery of the University of Pecs. The response rate was above 50% in both groups and complete pathological remission was achieved in 3 patients with gastric cancer and 17 patients with esophageal cancer. Based on our own experience and literature data, the development of seven new principles in surgical oncology were observed as the result of a very successful preoperative oncologic treatment. The desired free resection margin was reduced to the millimeter dimension in many cancer cases. Thus so-called organ-preserving procedures were made possible. Regarding the prognosis, the stage after the treatment became determinant. Complete histopathological remission could also be achievable in patients with oligometastases. In the case of a complete remission, the watch and wait tactics emerged as an option. Along the preoperative treatment of resectable colorectal liver metastases, there is no need to strive for complete remission. The treatment order of the primary tumor and its metastases can be reversed. Based on the improving results of oncology treatments, a reduction in surgical activity in the treatment of cancer patients is expected.

Genistein: A novel inhibitor of IL-6/IL-6R interface of the Interleukin-6–mediated STAT3 dependent pathway of carcinogenesis

Phytotherapy for breast cancer, the second most common cancer diagnosed among women and a leading cause of their death globally, may serve as an adjuvant therapy to combat adverse chemo-and radiotherapy challenges. IL-6/STAT3 signaling pathway, governing breast cancer progression, remains a favourite therapeutic target in developing phytotherapy. Therefore, identifying phytocompounds with novel targets influencing the IL-6/STAT3 pathway would help to develop phytotherapy for breast cancer. In this study, we demonstrate the novel binding site, i.e., the interface of IL-6 and IL-6Rα of the IL-6/STAT3 signaling pathway of cancer progression. Ten potent anticancer phytocompounds were analyzed for their binding with IL-6/IL-6Rα complex using molecular docking and molecular dynamics simulations. Among all, genistein showed excellent binding energy (-10.59 kcal/mol) with the IL-6/IL-6Rα interface of the STAT3 pathway. In cytotoxicity experiment, Genistein showed IC50 of 38 µM and 18 µM for 24 and 48 h, respectively, whereas quercetin showed IC50 of more than 50 µM and 35 µM at 24 h and 48 h, respectively on MDA-MB-453 breast cancer cell line. Based on bioinformatic analyses and cellular toxicity assay, we propose genistein as a potential therapeutic phytocompound to inhibit the IL-6/STAT3 pathway by blocking the interaction of IL-6 with the IL-6 receptor.

WT1 cancer vaccine for the treatment and prevention

Wilms’ tumor gene 1 (WT1) overexpresses in almost all kinds of hematological malignancies and solid tumors (hereinafter referred to as cancer). Therefore, WT1 protein is a ubiquitous tumor-associated antigen (TAA). Many clinical studies of WT1-targeted cancer immunotherapies (hereinafter referred to as WT1 cancer vaccine), including WT1 peptide vaccine, WT1 peptide-pulsed dendritic cell (WT1-DC) vaccine, and WT1 mRNA-electroporated dendritic cell (WT1 mRNA-DC) vaccine had been conducted for the treatment of almost all kinds of cancer. The clinical effect was promising, whereas the major side effects were the temporary fever and skin reaction on the vaccine injection sites and not significant. The appropriate combination therapy of WT1 cancer vaccine and chemotherapy enhanced WT1 immune response against cancer. Gemcitabine (GEM), for example, increased WT1 immune response through the promotion of the expression of WT1 antigen protein and HLA class I/II molecules in cancer. Furthermore, WT1 cancer vaccine immediately after hematopoietic stem cell transplantation (HSCT) induced sufficient WT1 immune response regardless of severe immunocompromised conditions and exerted sufficient clinical effect, suggesting that the immune condition immediately after HSCT should be suitable for the priming of WT1 immune response. Moreover, the combination therapy of WT1 cancer vaccine and immune checkpoint inhibitors (ICIs) was promising. Compared to the other TAAs, WT1 is especially unique in that it expresses not only in cancer cells but also in their stem cells at the quiescent state of cell-cycle, which are resistant to chemo-and radio-therapies. This uniqueness of WT1 largely contributes to cure cancer through the complete eradication of WT1-expressing cancer stem cells by WT1 immune response against them. Since the complete eradication of cancer stem cells is essential to cure cancer, and since only immune cells against cancer are considered to be able to kill the cancer stem cells at the quiescent state of cell-cycle, the introduction of immunotherapy, especially of WT1 cancer vaccine with sufficient safety is essential in the cure-oriented treatments of cancer. Accumulated clinical results suggest that WT1 cancer vaccine should be useful for cancer prevention, and the development of WT1 cancer prevention vaccine is awaited.

Impact of chemotherapy and radiotherapy on the survival of elderly esophageal cancer patients undergoing surgery: a SEER database analysis

BackgroundEsophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis.MethodsA total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram’s risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared.ResultsA better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45–0.68, P < 0.001), especially for those with tumors characterized by poor differentiation, large tumor size, advanced T staging, lymphatic metastasis, and distant metastasis (HR: 0.48, 95% CI 0.39–0.59, P < 0.001), while no benefit was observed among the low-risk patients. Furthermore, the newly established nomogram model might be better than the TNM (6th revision) staging system but more data needed.ConclusionAggressive treatments, such as surgery, chemotherapy, and radiotherapy, were considered effective for selected elderly patients with EC according to the newly established nomogram model.

The application of a conceptual framework to integrate oral health in childhood cancer care

Childhood cancer is a disease which is increasing in number. The good part is that if intervened early it can be treated with good prognosis. However, it is the utmost requirement of the medical fraternity to ease the quality of life of the paediatric patient in this journey. Oro-dental health and good oral health related quality of life is also deemed necessary for these childhood disease warriors. The provision of an inclusive facility of oral health care along with the paediatric cancer treatment has been emphasized. Utilization of services of preventive dentistry ranging from knowledge reinforcement of oral hygiene to awareness and treatment of early and late oral complications during the course of chemo-and radiotherapy is the ideal oral health care delivery approach in this population. The basic idea is to present an conceptual framework to integrate oral health into the childhood cancer care in an all embracing manner.

Adjuvant Treatment Following Irradical Resection of Stage I-III Non-small Cell Lung Cancer: A Population-based Study

Irradical (R1-2) resection for non-small cell lung cancer (NSCLC) is associated with a dismal prognosis. Adjuvant treatment attempts to improve survival outcomes, but evidence on the optimal strategy is limited. The purpose of this study was to compare overall survival (OS) between different adjuvant treatment strategies in these patients.Out of 8,528 patients with newly diagnosed NSCLC from 2015-2018, those with an R1-2 resection were identified from the Netherlands Cancer Registry. First, OS was compared between adjuvant treatment groups ‘no therapy’, ‘radiotherapy (RT) only’, ‘chemotherapy only’, and ‘chemo- and radiotherapy (CRT)’ using multinomial propensity score-weighted Cox regression analysis. Second, three 1:1 propensity score-matched sets were created for chemotherapy vs no chemotherapy, RT only vs no therapy, and CRT vs chemotherapy only. Kaplan-Meier and Cox regression analyses for OS were performed in each set.With a median follow-up of 23 months, 427 patients were selected. In the weighted regression analysis, compared to no adjuvant therapy, chemotherapy and CRT were associated with improved OS (HR 0.41, 95%CI: 0.22-0.76; and HR 0.55, 95%CI: 0.37-0.81, respectively), whereas RT was not (HR 1.04, 95%CI: 0.73-1.50). In the matched sets, OS was improved after chemotherapy (+/- RT) compared to no chemotherapy (HR 0.47, 95%CI: 0.32-0.69). No OS difference was observed between matched groups of RT only vs no adjuvant therapy (HR 1.13, 95%CI: 0.74-1.72), nor for CRT vs chemotherapy only (HR 1.37, 95%CI: 0.70-2.71). Adjuvant chemotherapy, but not radiotherapy, improves survival after an R1-2 resection in stage I-III NSCLC.

LncRNA MAGI2-AS3 inhibits tumor progression and angiogenesis by regulating ACY1 via interacting with transcription factor HEY1 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents the most common type of RCC in adults, characterized by hyper-vascularization and metastatic relapse. Surgical resection is the main treatment due to poor response of ccRCC to radio-and chemotherapy. However, the high complexity of tumor vasculature in ccRCC has thwarted effects to develop new therapeutic strategies for ccRCC. In this study, we identify the anti-angiogenic activity of MAGI2-AS3 in ccRCC. 86 paired samples of tumor tissues and adjacent no-tumor tissues were collected from ccRCC patients. Dual-luciferase reporter assay, RIP, and ChIP assays were employed to confirm interactions between MAGI2-AS3, transcription factor HEY1, and the ACY1 gene. In other studies, we assayed human ccRCC cells RLC-310 for their viability, migration and invasion using CCK-8 detection and transwell chamber systems. Angiogenesis was evaluated in the Matrigel-based human umbilical vein endothelial cell (HUVEC)-RLC-310 coculture model and immunohistochemical staining for vascular endothelial growth factor (VEGF) and CD31 in tumor tissues collected from a xenograft ccRCC mouse model. MAGI2-AS3 and ACY1 expression was downregulated in ccRCC tissues, and low expression of MAGI2-AS3 was associated with poor patient survival. Overexpression of MAGI2-AS3 could reduce ccRCC cell viability and migration, inhibit vessel-like tube formation of HUVECs in vitro, and repress tumor growth and angiogenesis in vivo. MAGI2-AS3 bound with HEY1 and reduced the HEY1 enrichment at the ACY1 promoter region, thus increasing ACY1 gene transcription. HEY1 knockdown or ACY1 overexpression that resisted MAGI2-AS3 knockdown was found in the in vivo and in vitro settings. The present study demonstrates that MAGI2-AS3 exerts tumor-suppressive, anti-angiogenic activities in ccRCC by modulating the HEY1/ACY1 pathway, thus lending support for conducting further investigations of anti-angiogenesis therapy for ccRCC.

The role of modern neoadjuvant radiotherapy in the combined treatment of locally advanced rectal cancer

Currently, rectal cancer is one of the leading pathologies in the structure of cancer morbidity and mortality, both in Russia and around the world. Thus, despite the improvement of existing and development of new methods for surgical treatment and anesthesia, as well as the introduction of the use of radio-and chemotherapy as an adjunct to surgical stage of the treatment, colorectal cancer still has a very high mortality rate among this cohort of cancer patients, and, primarily, due to the fact that approximately 30% of cases it is diagnosed at a very late stages of the disease. And, at the same time, combined and complex therapy to date does not contribute to improving the long-term results of special treatment, which, in the end, range from a complete response, in particular, during radiotherapy treatment, up to absolute resistance to its implementation. However, to date, there are already studies confirming the link between radioresistance and gene expression, which induce a response to the DNA damage checkpoint and increase the ability to repair DNA. At the same time, molecular biomarkers have a definite potential to predict the response to, in particular, neoadjuvant chemoradiotherapy for rectal cancer. This brief review examines the evolution and current state of neoadjuvant (preoperative) chemoradiotherapy for locally advanced rectal cancer (MRPC). At the same time, it should be emphasized that randomized studies and meta-analyses of recent publications justify the expediency of its use in this category of cancer patients. Modern strategies for treating patients with locally advanced rectal cancer and radiotherapy regimens used in this clinical situation are also briefly considered, as well as the prospects for using molecular genetic markers of radiosensitivity and their possible impact on the prognosis of this cancer.

Lung Cancer Attributed Mortality Among 316,336 Early Stage Breast Cancer Cases Treated by Radiotherapy and/or Chemotherapy, 2000-2015: Evidence From the SEER Database.

ObjectiveTo estimate the risk of death from lung cancer in patients treated for breast cancer (BC) in relation to the general population.MethodsBC data, covering 2000 to 2015, were extracted from the Surveillance, Epidemiology and End Results-18 (SEER-18) cancer registry database. A comparison of lung cancer attributed mortality between BC patients and the general population was performed using standardized mortality ratios (SMRs) and SMRs conditional on survival length (cSMRs). Prognostic factors of lung cancer mortality were identified using flexible parametric modelling. Our model adjusts the effect of downstream (histopathological BC tumor grade and hormone receptor status) and upstream (age at diagnosis, ethnicity, and marital status) factors.ResultsThe median follow-up was 6.4 years (interquartile range, 3.0–10.3 years). BC cases who received only radiotherapy (cSMR = 0.93; 95%CI: 0.77–1.13), only chemotherapy (cSMR = 0.91; 0.62–1.33), and radio-and chemotherapy (cSMR = 1.04; 0.77–1.39) had no evidence of increased lung cancer mortality relative to the general population. The adjusted model identified that lung cancer mortality was higher for women who were older at diagnosis compared to those <50 years (ranging from HR50-59 = 3.41 [95%CI: 2.72–4.28] to HR70-79 = 10.53 [95%CI: 8.44–13.13]) and for cases with negative estrogen and progesterone receptors (HR =1.38; 95% CI: 1.21–1.57). Compared to married cases, widowed, divorced, single or others had a 76%, 45%, and 25% higher hazard of lung cancer mortality, respectively. Lung cancer mortality was lower for American Indian/Alaska Native and Asian/Pacific Islander ethnicities (HR = 0.51; 95% CI: 0.40–0.64) compared to BC cases with white ethnic background.ConclusionsThere is no evidence for a higher lung cancer mortality in BC patients when compared to the general population.

Descriptive Analysis of Patients with Gastric Tumors Referred to the Largest Emergency Hospital in Oltenia Region-Romania, Between 2015-2020.

Gastric cancer represents the third most frequent cause of death worldwide, with the treatment being impaired also by the fact that patients present in the late stages of disease progression. We have aimed here to evaluate the main clinical and pathological features of all recorded cases of gastric tumor patients presented between January 2015 and December 2020 within the Emergency County Hospital of Craiova. Our retrospective analysis identified a total number of 745 cases, and showed a relative homogenous distribution of the age of the patients / year, with the peak age at presentation of 70-80 years old, and with males having a slightly higher prevalence compared to females. There was no correlation of the number of hospitalization days with the localization of the tumor, but the patients in the age group 60-70 years of age tended to show longer hospitalization times compared to the rest of the age groups. Also, pyloric/ antral tumors tended to present at younger ages compared to other localizations, and interestingly, these patients also represented most of the casuistry. Altogether, the distribution of gastric cancer patients’ features did not change significantly in the last 5 years despite treatment advances (especially chemo-and radiotherapy), and the advanced stage of presentation call for a more aggressive detection and increased awareness of the population for this frequent pathology.

Promising Therapy in Lung Cancer: Spotlight on Aurora Kinases

Simple SummaryLung cancer has remained one of the major causes of death worldwide. Thus, a more effective treatment approach is essential, such as the inhibition of specific cancer-promoting molecules. Aurora kinases regulate the process of mitosis—a process of cell division that is necessary for normal cell proliferation. Dysfunction of these kinases can contribute to cancer formation. In this review, we present studies indicating the implication of Aurora kinases in tumor formation, drug resistance, and disease prognosis. The effectivity of using Aurora kinase inhibitors in the pre-clinical and clinical investigations has proven their therapeutic potential in the setting of lung cancer. This work may provide further information to broaden the development of anticancer drugs and, thus, improve the conventional lung cancer management.Despite tremendous efforts to improve the treatment of lung cancer, prognosis still remains poor; hence, the search for efficacious therapeutic option remains a prime concern in lung cancer research. Cell cycle regulation including mitosis has emerged as an important target for cancer management. Novel pharmacological agents blocking the activities of regulatory molecules that control the functional aspects of mitosis such as Aurora kinases are now being investigated. The Aurora kinases, Aurora-A (AURKA), and Aurora B (AURKB) are overexpressed in many tumor entities such as lung cancer that correlate with poor survival, whereby their inhibition, in most cases, enhances the efficacy of chemo-and radiotherapies, indicating their implication in cancer therapy. The current knowledge on Aurora kinase inhibitors has increasingly shown high potential in ensuing targeted therapies in lung malignancies. In this review, we will briefly describe the biology of Aurora kinases, highlight their oncogenic roles in the pre-clinical and clinical studies in lung cancer and, finally, address the challenges and potentials of Aurora kinases to improve the therapy of this malignancy.