Survival Rate Of Cancer Patients Research Articles

A bioinformatics analysis of the clinicopathological and prognostic significance of FAM64A mRNA expression in gynecological cancers

FAM64A is a mitotic regulator which promotes cell metaphase-anaphase transition and is highly expressed in a cell-cycle-dependent manner. In this study, we examined the clinicopathological and prognostic significance of FAM64A mRNA expression in gynecological cancers. We conducted a bioinformatics analysis of FAM64A mRNA expression using Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), xiantao, The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier (KM) plotter databases. FAM64A expression was elevated in breast, cervical, endometrial, and ovarian cancers when compared with normal tissue. Expression was positively correlated with white race, low T stages, infiltrating ductal carcinoma, or favourable PAM50 classification in breast cancer patients, and with clinical stage, histological grade and TP53 mutation, and endometrial cancer serous subtype. FAM64A expression was negatively associated with overall and/or recurrence-free survival rates in breast and endometrial cancer patients, while the opposite was observed in cervical and ovarian cancer patients. FAM64A functioned as an independent predictor of overall and disease-specific survival in breast cancer patients. FAM64A-correlated genes were involved in ligand-receptor interactions, and chromosomal, cell cycle, and DNA replication processes in breast, cervical, endometrial and ovarian cancers. Top hub genes primarily included cell cycle-related proteins in breast cancer, mucins and acetylgalactosaminyl transferases in cervical cancer, kinesin family members in endometrial cancer, and synovial sarcoma X and the cancer/testis antigen in ovarian cancer. FAM64A mRNA expression was positively related to Th2 cell infiltration, but negatively associated with neutrophil and Th17 cell infiltration in breast, cervical, endometrial, and ovarian cancers. FAM64A expression may be considered a potential biomarker reflecting carcinogenesis, histogenesis, aggressive behaviour, and prognosis in gynecological cancers. Impact statement What is already known on this subject? FAM64A is located in cell nucleolar and nucleoplasmic regions, and during mitosis it putatively controls metaphase-to-anaphase transition. FAM64A appears to regulate different physiological processes, including apoptosis, tumorigenesis, neural differentiation, stress responses, and the cell cycle. What the results of this study add? FAM64A expression was up-regulated in breast, cervical, endometrial, and ovarian cancers, and positively correlated with white race, low T stages, infiltrating ductal carcinoma, or favourable PAM50 classification in breast cancer patients, and with clinical stage, histological grade, and TP53 mutation, and a serous subtype in endometrial cancer. FAM64A expression was negatively associated with overall and/or recurrence-free survival rates in breast and endometrial cancer patients, while the opposite was observed in cervical and ovarian cancer patients. FAM64A functioned as an independent predictor of overall and disease-specific survival in breast cancer. FAM64A-correlated genes were involved in ligand-receptor interactions, chromosomal, cell cycle, and DNA replication processes, while FAM64A mRNA expression was positively related to Th2 cell infiltration but negatively correlated with neutrophil and Th17 cell infiltration in four gynecological cancers. What the implications of these findings for clinical practice and/or further research? In the future, abnormal FAM64A mRNA expression may serve as a biomarker of carcinogenesis, histogenesis, aggressiveness, and prognosis in gynecological malignancies.

IL-6 as a predictor of survival rate in liver metastatic breast cancer patients with Covid-19 infection: A case series

Introduction and importanceBreast cancer is the most common type of cancer in women, with 30 % being metastatic breast cancer. Cancer is known to be a comorbid Covid-19 infection. Interleukin-6 (IL-6) is one of the findings of inflammatory activity due to Covid-19 infection. We report IL-6 levels as a prognostic factor for survival rate in patients with liver metastatic breast cancer. Case presentationWe report five cases of liver metastatic breast cancer with various types of primary breast cancer. All patients are infected with Covid-19. IL-6 levels were reported to be elevated in all five patients. All patients were treated according to the national guidelines for the care of Covid-19 patients. All patients are reported to have deceased after being treated for Covid-19 infection. Clinical discussionMetastatic breast cancer has a low prognostic rate. Cancer has been recognized as one of the comorbidities and increases the severity and mortality of Covid-19 infection. Elevated levels of IL-6 are caused by an immune response to infection, and can worsen the outcome of breast cancer patients. Changes in IL-6 levels implicate the survival rate of metastatic breast cancer patients and outcomes during the treatment of Covid-19 infection. ConclusionElevated levels of IL-6 can be a prognostic factor of the survival rate of metastatic breast cancer patients during the treatment of Covid-19 infection.

Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR-206 expression.

Colon cancer is a great threat to human health. Curcumin, as a traditional Chinese medicine extract with anti-tumor and anti-inflammatory effects, can affect the development of diverse human diseases including cancer. The aim of this research was to probe the mechanism by which curcumin regulates colon cancer progression. Colon cancer cells were processed with graded concentrations of curcumin. The proliferation and apoptosis of the treated cells were determined by MTT, colony formation assay and flow cytometry. Expression of signaling pathway-related proteins and programmed death-ligand 1 (PD-L1) was measured by western blotting. The effect of curcumin on tumor cell growth was verified through T cell-mediated killing and ELISA assays. The relationship between target gene expression and the survival rate of colon cancer patients was analyzed by a survival curve. Curcumin treatment restrained proliferation and accelerated apoptosis of colon cancer cells. It elevated miR-206 expression, which in turn affected colon cancer cell function. miR-206 enhanced colon cancer cell apoptosis and inhibited PD-L1 expression; thus, curcumin enhanced the killing effect of T cells on tumor cells by suppressing PD-L1 through inhibiting the JAK/STAT3 pathway. Patients with high expression of miR-206 had better survival rates than those with low expression. Curcumin can regulate miR-206 expression and inhibit the malignant behavior of colon cancer cells and enhance T cell killing through the JAK/STAT3 pathway.

Preservation of fertility in patients with testicular germ cell tumors: oncological, legal, and religious aspects

Survival rates for cancer patients continue to steadily increase due to improvement of effectiveness of current treatments. However, despite significant oncological results, one should not forget about the quality of life of this cohort of patients, in particular those who undergo gonadotoxic cancer therapy with development of premature ovarian failure in women and azoospermia in men. Preservation of fertility in both women and men with cancer is currently possible and should be integrated at all levels of cancer care. In this regard, the main purpose of this review is to consider the topic of fertility in men treated for cancer in the context of various aspects of human life.

Survival Rate of Lung Adenocarcinoma Patients Receiving EGFR - Tyrosine Kinase Inhibitor Targeted Therapy

Globally, lung cancer is by far the leading cause of death by cancer-which contribute to 2.094 million death-with the highest toll from cancer being 1.8 million. Currently, lung cancer therapy has developed from chemotherapy to targeted therapy, such as Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI). This study aimed to assess the survival rate of adenocarcinoma cell lung cancer patients who received EGFR-TKI therapy at the Pulmonary Clinic of Dr. Saiful Anwar General Hospital Malang. This study was a retrospective study using patient medical records between 2017 and 2020. The data were processed and analyzed using the Chi-Square test. The number of samples was 117 patients consisting of 63 patients receiving Gefitinib therapy, 36 patients receiving Afatinib therapy, and 18 patients receiving Erlotinib therapy. There were no significant differences between variables of age, sex, smoking history, stage, and exon mutations with 1-year survival. Gefitinib therapy has a higher average survival time than Afatinib and Erlotinib. However, the 1-year survival rate (YSR) was highest on Afatinib. The Middle Survival (MS) of the three regimens is almost the same, about 300 days. Statistical data showed no relationship between survival and the treatment regimen given (p=0.187). The most common side effect of TKI is skin rash. This research should be carried out with a larger sample to minimize bias.

Ethyl acetate extract of Antenoron Filiforme inhibits the proliferation of triple negative breast cancer cells via suppressing Skp2/p21 signaling axis

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis of the any breast cancer subtype, and the efficient therapeutical treatment is extremely limited. Antenoron filiforme (Thunb.) Roberty & Vautier (AF) is a Traditional Chinese Medicine (TCM), which is well-known for a diverse array of pharmacological activities, including but not limited to anti-inflammatory, antioxidant and anti-tumors properties. Clinically, AF is commonly prescribed for the treatment of gynecological diseases. PurposeSince TNBC is one of the worst gynecological diseases, the objective of this research is to study the anti-TNBC function of the ethyl acetate extract (EAE) of AF (AF-EAE) and disclose its mechanism of action. Materials and methodsWith the aim of elucidating the underlying molecular mechanism and possible chemical basis of AF-EAE in the treatment of TNBC, a comprehensive approach combining system pharmacology and transcriptomic analysis, functional experimental validation, and computational modeling was implemented. Firstly, the potential therapeutic targets of AF-EAE treating TNBC were analyzed by systemic pharmacology and transcriptome sequencing. Subsequently, cell viability assays, cell cycle assays, and transplantation tumor assays were employed to detect the inhibitory effect of AF-EAE on TNBC. Apart from that, the western blot and RT-qPCR assays were adopted to verify its mechanism of action. Finally, the potential chemical basis of anti-TNBC function of AF-EAE was screened through molecular docking and validated by molecular dynamics. ResultsThis study analyzed the differentially expressed genes after AF-EAE treatment by RNA-sequencing (RNA-seq). It was found that most of the genes were abundant in the gene set termed “cell cycle”. Besides, AF-EAE could suppress the proliferation of TNBC cells in vitro and in vivo by inhibiting the function of Skp2 protein. AF-EAE could also lead to the accumulation of p21 and a decrease of CDK6/CCND1 protein, thereby stalling the cycle of cell in the G1/S stage. Notably, clinical data survival analysis clearly demonstrated that Skp2 overexpression has been negatively correlated with survival rates in breast cancer (BC) patients. Further, as suggested by molecular docking and molecular dynamics, the quercetin and its analogues of AF-EAE might bind to Skp2 protein. ConclusionIn summary, AF-EAE inhibits the growth of TNBC in vitro and in vivo through targeting Skp2/p21 signaling pathway. While providing a novel potential drug for treating TNBC, this study might establish a method to delve into the action mechanism of TCM.

18F-FDG PET/CT Image Deep Learning Predicts Colon Cancer Survival.

Colon cancer is a type of cancer that begins in the large intestine. In the process of efficacy evaluation, postoperative recurrence prediction and metastasis monitoring of colon cancer, traditional medical image analysis methods are highly dependent on the personal ability of the doctors. In the process of patient treatment, it not only increases the workload and work pressure for doctors, but also has some problems with traditional medical image analysis methods. Moreover, the traditional medical image analysis methods have problems such as insufficient prediction accuracy, slow prediction speed, and the risk of errors in prediction. When analyzing 18F-FDG PET/CT images by traditional medical image analysis methods, it is easy to cause problems such as untimely treatment plans and errors in diagnosis, which will adversely affect the survival of colon cancer patients. Although 18F-FDG PET/CT images have certain advantages in image clarity and accuracy compared with traditional medical imaging methods, the analysis method based on 18F-FDG PET/CT images also has certain effects in predicting the survival of colon cancer patients, but there are still many shortcomings: the 18F-FDG PET/CT image analysis method overly relies on the technical advantages of 8F-FDG PET/CT images; in the analysis and prediction of image data, it has not gotten rid of the dependence on the personal medical quality of the doctors; traditional medical image analysis methods are still used when analyzing and predicting images; there is no breakthrough in image analysis effects. In order to solve these problems, this paper combined deep learning theory, using three algorithms of the improved RBM algorithm, image feature extraction method based on deep learning, and regression neural network to analyze and predict 18F-FDG PET/CT images, and applied some algorithms to analyze and predict 18F-FDG PET/CT images, and also established a deep learning-based 18F-FDG PET/CT image survival analysis prediction model. Four aspects survival prediction accuracy, survival prediction speed, survival prediction precision, and physician satisfaction were studied through this model. The research results have shown that compared with traditional medical image analysis methods, the prediction accuracy of 18F-FDG PET/CT image survival analysis prediction model based on deep learning is improved by 0.83%, and the prediction speed is improved by 3.42%, as well as the prediction precision increased by 6.13%. The research results show that the deep learning-based 18F-FDG PET/CT image survival analysis prediction model established in this paper is of great significance to improve the survival rate of colon cancer patients, and also promotes the development of the medical industry.

HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer.

Cisplatin resistance is a crucial factor affecting ovarian cancer patient's survival rate, but the primary mechanism underlying cisplatin resistance in ovarian cancer remains unclear, and this prevents the optimal use of cisplatin therapy. Maggot extract (ME) is used in traditional Chinese medicine for patients with comas and patients with gastric cancer when combined with other drug treatments. In this study, we investigated whether ME enhances the sensitivity of ovarian cancer cells to cisplatin. Two ovarian cancer cells-A2780/CDDP and SKOV3/CDDP-were treated with cisplatin and ME in vitro. SKOV3/CDDP cells that stably expressed luciferase were subcutaneously or intraperitoneally injected into BALB/c nude mice to establish a xenograft model, and this was followed by ME/cisplatin treatment. In the presence of cisplatin, ME treatment effectively suppressed the growth and metastasis of cisplatin-resistant ovarian cancer in vivo and in vitro. RNA-sequencing data showed that HSP90AB1 and IGF1R were markedly increased in A2780/CDDP cells. ME treatment markedly decreased the expression of HSP90AB1 and IGF1R, thereby increasing the expression of the proapoptotic proteins p-p53, BAX, and p-H2AX, while the opposite effects were observed for the antiapoptotic protein BCL2. Inhibition of HSP90 ATPase was more beneficial against ovarian cancer in the presence of ME treatment. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in promoting the increased expression of apoptotic proteins and DNA damage response proteins in SKOV3/CDDP cells. Inhibition of cisplatin-induced apoptosis and DNA damage by HSP90AB1 overexpression confers chemoresistance in ovarian cancer. ME can enhance the sensitivity of ovarian cancer cells to cisplatin toxicity by inhibiting HSP90AB1/IGF1R interactions, and this might represent a novel target for overcoming cisplatin resistance in ovarian cancer chemotherapy.

Nuclear receptor co-repressor NCOR2 and its relation to GPER with prognostic impact in ovarian cancer.

The significance of the non-classical G-protein-coupled estrogen receptor (GPER) as positive or negative prognostic factor for ovarian cancer patients remains still controversial. Recent results indicate that an imbalance of both co-factors and co-repressors of nuclear receptors regulates ovarian carcinogenesis by altering the transcriptional activity through chromatin remodeling. The present study aims to investigate whether the expression of the nuclear co-repressor NCOR2 plays a role in GPER signaling which thereby could positively impact overall survival rates of ovarian cancer patients. NCOR2 expression was evaluated by immunohistochemistry in a cohort of 156 epithelial ovarian cancer (EOC) tumor samples and correlated with GPER expression. The correlation and differences in clinical and histopathological variables as well as their effect on prognosis were analyzed by Spearman's correlation, Kruskal-Wallis test and Kaplan-Meier estimates. Histologic subtypes were associated with different NCOR2 expression patterns. More specifically, serous and mucinous EOC demonstrated a higher NCOR2 expression (P = 0.008). In addition, high nuclear NCOR2 expression correlated significantly with high GPER expression (cc = 0.245, P = 0.008). A combined evaluation of both high NCOR2 (IRS > 6) and high GPER (IRS > 8) expression revealed an association of a significantly improved overall survival (median OS 50.9 versus 105.1months, P = 0.048). Our results support the hypothesis that nuclear co-repressors such as NCOR2 may influence the transcription of target genes in EOC such as GPER. Understanding the role of nuclear co-repressors on signaling pathways will allow a better understanding of the factors involved in prognosis and clinical outcome of EOC patients.

Survival of cervical cancer patients in Brunei Darussalam: 2002–2017

ObjectiveCervical cancer is the fourth leading cause of cancer deaths among Bruneian women. This study aims to investigate the survival rate of cervical cancer patients in Brunei Darussalam between 2002 and 2017, to compare survival of cervical cancer patients between two periods: 2002–2009 and 2010–2017 and to identify prognostic factors of cervical cancer. MethodsA retrospective cohort study on cervical cancer patients registered in Brunei Darussalam Cancer Registry between 2002 and 2017. De-identified data from the registry was extracted and survival analysis was performed using Kaplan-Meier estimator, log-rank test and multiple Cox regression analysis. ResultsThe 1-, 3- and 5-year survival rates of cervical cancer patients in Brunei Darussalam were 87.3%, 77.4% and 72.5% respectively from 2002 to 2017. The 5-year survival rate for 2002–2009 and 2010–2017 were 77.3% and 69.1% respectively. The risk of mortality was significantly higher in 2010–2017 compared to 2002–2009 after adjusting for variables (Adjusted HR = 1.59; 95% CI: 1.08, 2.40; p = 0.019). Patients with distant cancer (Adjusted HR = 11.21; 95% CI: 6.18, 20.30; p < 0.001) had the highest risk of mortality. ConclusionThe 5-year survival rate of cervical cancer patients in Brunei Darussalam was 72.5%, which ranks relatively high globally. However, increased mortality among elderly patients, and patients diagnosed with cervical cancers at the later stages, calls for public health efforts to raise awareness, early detection, and disease management.

Effectiveness of Virtual Reality in Symptom Management of Cancer Patients: A Systematic Review and Meta-Analysis.

Although the survival rate of cancer patients has been increasing, such patients often experience severe physical and psychological burdens due to the effects of the disease and therapy. Multiple virtual reality (VR)-based interventions have been used to help improve physical and psychological symptoms and quality of life in cancer patients. This study aimed to assess the effects of VR-based interventions on anxiety, pain, depression, fear, distress, and quality of life in cancer patients. We conducted systematic searches in the PubMed, Web of Science, CINAHL, EMBASE, Cochrane Library, Scopus and APA PsycINFO databases from their inception to August 16, 2022. Two reviewers independently selected studies and extracted articles that met strict inclusion and exclusion criteria. Quality assessments of the included studies were performed according to the Cochrane risk assessment tool, and data analysis was performed using RevMan 5.4 software. A total of 12 studies including 425 participants in the intervention group and 400 participants in the control group were selected for the final analysis. The results showed a significant difference between the VR and control groups for anxiety (standard mean difference [SMD] =-0.83, 95% CI -1.25 to -0.42, P < 0.001), SMD=pain (SMD =-0.86, 95% CI -1.36 to -0.35, P < 0.001), depression (SMD=-0.46, 95% CI -0.74 to -0.18, P=0.001), fear (MD=-0.82, 95% CI -1.60 to -0.03, P=0.04), and distress (SMD=-1.16, 95% CI -1.96 to -0.37, P=0.004). However, no significant difference was observed in quality of life (SMD=1.01, 95% CI -0.67 to 2.70, P=0.24). VR interventions were effective in improving physical and psychological symptoms in cancer patients. Due to the limited number of studies, small sample sizes, and moderate to high heterogeneity, these results should be interpreted with caution. More rigorous, comprehensive and high-quality randomized controlled trials (RCTs) are needed to validate the results of this study. PROSPERO International Prospective Register of Systematic Reviews CRD42022304931;https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304931.

A novel microRNA-182/Interleukin-8 regulatory axis controls osteolytic bone metastasis of lung cancer

Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non–small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis.

Superior Sensibility after Full Breast Reconstruction with Autologous Fat Transfer.

With developments in screening and treatment, survival rates of breast cancer patients are increasing, and so is the number of women opting for breast reconstruction to improve their quality of life. One factor that could play an important role in improving the quality of life is breast sensibility. Therefore, the aim of this study was to explore breast sensibility in participants of the Breast Reconstruction with External Preexpansion and Autologous Fat Transfer versus Standard Therapy trial: an ongoing randomized controlled trial comparing breast reconstruction with autologous fat transfer (AFT) versus implant-based reconstruction (IBR). This study was conducted on participants of the Breast Reconstruction with External Preexpansion and Autologous Fat Transfer versus Standard Therapy trial who were at least 12 months after final surgery. Semmes-Weinstein monofilaments were used to measure skin sensibility in breast cancer patients who underwent breast reconstruction with either AFT or IBR following their mastectomy. A total of 46 patients were included in this study, resulting in 62 breast reconstructions (28 AFT breasts and 34 IBR breasts). Significantly higher mean monofilament values were found for skin sensibility after AFT (-0.7; P < 0.001), clinically correlating to "diminished protective function," as opposed to the IBR group, with clinical values indicating "loss of protective function." In this study, the authors found that breast cancer patients who underwent a mastectomy had a significantly better sensibility of the breast following AFT for total breast reconstruction as compared with IBR. Larger studies that include null measurements are required to further explore these noteworthy results of AFT. Therapeutic, II.

Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors.

The advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%. We recently reported about urinary flow cytometry-based detection of urinary PD-L1-positive (PD-L1+) kidney cells correlating with tubular PD-L1-positivity that reflected susceptibility to develop ICI-related nephrotoxicity as an irAE attending ICI treatment. Therefore, we designed a study protocol to evaluate urinary detection of PD-L1+ kidney cells as a tool for non-invasive biomonitoring of renal complications in cancer patients treated with ICIs. A prospective, controlled, non-interventional, longitudinal, single-center observational study will be conducted at the Department of Nephrology and Rheumatology of the University Medical Center Göttingen, Germany. We intend to enroll approximately 200 patients treated with immunotherapy from the Departments of Urology, Dermatology, and Hematology and Medical Oncology of the University Medical Center Göttingen, Germany. First, we will assess clinical, laboratory, histopathological, and urinary parameters in addition to urinary cell collection. Then, we will perform a correlative analysis between urinary flow cytometry of different PD-L1+ cell of renal origin with the onset of ICI-related nephrotoxicity. Because of growing ICI-treatment applicability with an expectable incidence of renal complications, providing cost-efficient and easily performable diagnostic tools for treatment-attendant and non-invasive biomonitoring becomes vital to improve both renal and overall survival rates in cancer patients receiving immunotherapy. https://www.drks.de, DRKS-ID DRKS00030999.

Benefits of β-blockers in cancer treatment

Cancer is one of the leading causes of death in the world. Researchers keep attempting to develop therapy modalities to decrease the mortality and morbidity of cancer patients by trying to comprehend the effect of sympathetic nerves (through catecholamine and adrenergic receptors) in cancer development. Catecholamine activation in β-adrenergic receptors (β1-AR, β2-AR, and β3-AR) may influence cytokine and cancer immunity system, initiate tumorigenesis, stimulate tumor-associated macrophage and angiogenesis, influence tumor microenvironment, and facilitate cancer cell metastasis, leading to increased progressivity of cancer cells. β-blockers may inhibit catecholamine on β-AR and various types of paths needed for cancer cells to develop. β-blockers also stimulate cancer cell apoptosis, decrease pro-inflammatory mediators and growth factors of cancer cells. In addition, β-blockers also have benefits as supplementary cancer therapy, increase chemoradiotherapy sensitivity, decrease cardiotoxicity, and improve cancer cachexia. The benefits of β-blockers are expected to reduce morbidity and increase the survival rates of cancer patients. This review comprehensively assesses the benefit of b-blockers as a part of the complete management of cancer patients.

Pogostone attenuates osteolysis in breast cancer by inhibiting the NF-kB and JNK signaling pathways of osteoclast

AimsBreast cancer is the most prevalent cancer in females, and approximately 70 % of all patients have evidence of metastatic bone disease, which substantially affects the quality of life and survival rate of breast cancer patients. Osteoporosis has become a global public health problem, and the abnormal activation of osteoclasts is the key to the progression of osteoporosis and the key to both diseases lies in the osteoclasts. Effective drug treatments are lacking and there is an urgent need to explore new drugs. Materials and methodsWe observed the effects of pogostone (PO) on osteoclast differentiation, bone resorption function and other indicators, and F-actin ring formation by using Trap staining, SEM and immunofluorescence, and further explored the targets of pogostone in regulating osteoclast differentiation and function using qPCR and Western Blot. In addition, we used CCK 8, Transwell, and flow cytometry to study the effects of pogostone on proliferation, invasion, migration, and apoptosis of MDA-MB-231 cells. Animal models were also constructed for in vivo validation. Key findingsPogostone inhibits osteoclast differentiation, bone resorption, formation of F-actin ring, and the expression of specific genes by attenuated NF-kB degradation and phosphorylation of JNK. In vitro, pogostone suppresses invasion of breast cancer cells, migration, and promotes their apoptosis. In mouse models, pogostone attenuated osteoclast formation and bone resorption, blocked breast cancer cells migration, and supprsed breast cancer-induced osteolysis and ovariectomized (OVX)-mediated osteoporosis. SignificanceThese biological functions of pogostone make it a potential drug for treatment of breast cancer-associated bone metastasis in the future.

Dual functionality of pyrimidine and flavone in targeting genomic variants of EGFR and ER receptors to influence the differential survival rates in breast cancer patients

Abstract Breast cancer ranks as one of the most prevalent forms of cancer and stands as the primary global cause of mortality among women. Overexpression of EGFR and ER receptors or their genomic alterations leads to malignant transformation, disease aggression and is linked to poor patient survival outcomes. The clinical breast cancer patient’s genomic expression, survival analysis, and computational drug-targeting approaches were used to identify best-hit phytochemicals for therapeutic purposes. Breast cancer patients have genomic alterations in EGFR (4%, n = 5699) and ER (9%, n = 8461), with the highest proportion being missense mutations. No statistically significant difference was observed in the patient survival rates between the altered and unaltered ER groups, unlike EGFR, with the lowest survival rates in the altered group. Computational screening of natural compound libraries (7711) against each EGFR (3POZ) and ER (3ERT) receptor shortlists the best-hit 3 compounds with minimum docking score (ΔG = −7.9 to −10.8), MMGBSA (−40.16 to −51.91 kcal/mol), strong intermolecular H-bonding, drug-like properties with least kd, and ki. MD simulation studies display stable RMSD, RMSF, and good residual correlation of best-hit common compounds (PubChem ID: 5281672 and 5280863) targeting both EGFR and ER receptors. In vitro, studies revealed that these common drugs exhibited a high anti-proliferative effect on MCF-7 and MDA-MB-231 breast cancer cells, with effective IC50 values (15–40 μM) and lower free energy, kd, and ki (5281672 &amp;gt; 5280863 &amp;gt; 5330286) much affecting HEK-293 non-cancerous cells, indicating the safety profile. The experimental and computational correlation studies suggest that the highly expressed EGFR and ER receptors in breast cancer patients having poor survival rates can be effectively targeted with best-hit common potent drugs with a multi-target therapeutic approach. Insight Box: The findings of this study provide valuable insights into the genomic/proteomic data, breast cancer patient’s survival analysis, and EGFR and ER receptor variants structural analysis. The genetic alterations analysis of EGFR and ER/ESR1 in breast cancer patients reveals the high frequency of mutation types, which affect patient’s survival rate and targeted therapies. The common best-hit compounds affect the cell survival patterns with effective IC50, drug-like properties having lower equilibrium and dissociation constants demonstrating the anti-proliferative effects. This work integrates altered receptor structural analysis, molecular interaction-based simulations, and ADMET properties to illuminate the identified best hits phytochemicals potential efficacy targeting both EGFR and ER receptors, demonstrating a multi-target therapeutic approach.

Prognostic value of O6-methylguanine-DNA methyltransferase hypermethylation and expression in head and neck cancer: A systematic review and meta-analysis

O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that maintains the stability of genetic information. MGMT is a strong prognostic biomarker in patients with glioblastoma. However, the effect of its gene hypermethylation and expression on the survival rate of head and neck cancer (HNC) patients is still disputed. Therefore, we conducted a meta-analysis to evaluate the prognostic value of MGMT hypermethylation and expression in HNC patients. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered at the International Prospective Register of Systematic Reviews (CRD42021274728). Literature related to the survival rate of HNC patients and MGMT was systematically searched in PubMed, Embase, The Cochrane Library and Web of Science electronic databases (published from inception to February 1, 2023). The association was evaluated by the combined hazard ratio (HR) and related 95% confidence interval (CI). Two authors independently screened all records and extracted the data. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. All of the statistical tests used in this meta-analysis were conducted with Stata 12.0 software. We included 5 studies with 564 HNC patients for the meta-analysis. All of the included patients were primary tumors and underwent surgical resection without prior radiotherapy or chemotherapy therapy. No significant heterogeneity was noted between MGMT and overall survival, MGMT and disease-free survival, and a fixed-effects model was used. HNC patients with MGMT hypermethylation and low expression had a poor prognosis, with pooled HR for overall survival (HR = 1.23, 95% CI: 1.10-1.38, P < .001) and disease-free survival (HR = 2.28, 95% CI: 1.45-3.58, P < .001). Subgroup analysis stratified by molecular abnormalities, such as hypermethylation or low expression, showed similar results. The insufficient number of trials included in our study encountered high risk of bias and may increase the deviation of the final meta-analysis results. HNC patients with MGMT hypermethylation and low expression were more likely to exhibit poorer survival. MGMT hypermethylation and low expression can predict survival in patients with HNC.

Stearoyl-CoA Desaturases1 Accelerates Non-Small Cell Lung Cancer Metastasis by Promoting Aromatase Expression to Improve Estrogen Synthesis.

Metastases contribute to the low survival rate of non-small cell lung cancer (NSCLC) patients. Targeting lipid metabolism for anticancer therapies is attractive. Accumulative evidence shows that stearoyl-CoA desaturases1 (SCD1), a key enzyme in lipid metabolism, enables tumor metastasis and the underlying mechanism remains unknown. In this study, immunohistochemical staining of 96 clinical specimens showed that the expression of SCD1 was increased in tumor tissues (p < 0.001). SCD1 knockdown reduced the migration and invasion of HCC827 and PC9 cells in transwell and wound healing assays. Aromatase (CYP19A1) knockdown eliminated cell migration and invasion caused by SCD1 overexpression. Western blotting assays demonstrated that CYP19A1, along with β-catenin protein levels, was reduced in SCD1 knocked-down cells, and estrogen concentration was reduced (p < 0.05) in cell culture medium measured by enzyme-linked immunosorbent assay. SCD1 overexpression preserving β-catenin protein stability was evaluated by coimmunoprecipitation and Western blotting. The SCD1 inhibitor A939572, and a potential SCD1 inhibitor, grape seed extract (GSE), significantly inhibited cell migration and invasion by blocking SCD1 and its downstream β-catenin, CYP19A1 expression, and estrogen concentration. In vivo tumor formation assay and a tail vein metastasis model indicated that knockdown of SCD1 blocked tumor growth and metastasis. In conclusion, SCD1 could accelerate metastasis by maintaining the protein stability of β-catenin and then promoting CYP19A1 transcription to improve estrogen synthesis. SCD1 is expected to be a promised therapeutic target, and its novel inhibitor, GSE, has great therapeutic potential in NSCLC.

Abstract 5908: Specific gut microbial community is associated with specific cancer types: A strategy for cancer detection and prevention

Abstract Background: Cancer is the second leading cause of death in the world. Unfortunately, survival rates for cancer patients have stayed poor for many decades. Thus, there is an unmet need to identify novel strategies for early cancer detection and prevention. Recent studies suggest that the gut microbiome including bacteria may have a role in cancer initiation and progression. These bacteria play a vital role in maintaining homeostasis in the body. An imbalance in the bacterial composition may cause diseases including cancer. This evidence led us to hypothesize that the changes in the composition of the gut microbiome can be used as a biomarker for early cancer detection. To test this hypothesis, we focused on analyzing the microbial community of colorectal and blood cancers, which have poor survival rates. Methods and Results: To analyze the association of cancer with the microbiome, we used a published microbiome dataset of leukemic and healthy individuals that were collected by sequencing stool samples (Oliver et al., 2022). We identified that specific bacteria are either abundant, such as Faecalibacterium (1.17 fold), or reduced, such as Clostridium (0.32 fold, p value=0.0029), in leukemia patients compared to healthy controls. We observed similar correlations by analyzing the published colorectal cancer data (Flemer et al., 2017) in which Prevotella increased by 3.75 fold and Escherichia/Shigella increased by 4.0 fold in colorectal cancer while Blautia is reduced compared to healthy controls. Faecalibacterium, which is abundant in leukemia, is reduced in colorectal cancer. Further, we found that treatment of leukemia patients normalized the abundance of these bacteria to the level of healthy patients. To improve analysis efficiency, we applied machine learning algorithms to predict the presence of cancer in patients based on the composition of bacteria, age, gender, and symptoms. Among the tested algorithms, the decision tree and Random Forest both had very high false-negative rates, with 45.5% and 40% respectively, as well as having low sensitivities, with 50% and 60% respectively. The support Vector Machine had a suboptimal false-negative rate of 28.6% and good sensitivity of 80%. Finally, the Neural network had a good false-negative rate of 16.7% and great sensitivity of 90%. Overall, our results suggest that different cancers have an abundance of specific bacteria that can be used as biomarkers for cancer detection. Conclusion: We demonstrate that the increased abundance of certain bacteria in the microbiome can be used as a biomarker for cancer detection. Our data set was small for this project, but the machine learning approaches can be used to further predict cancer These are clinically relevant findings as a microbiome test would be non-invasive and easily accessible that can be performed at a routine checkup. Citation Format: Ekansh Mittal, Andrew Oliver, Kenza El Alaoui, Carolyn Haunschild, Julio Avelar-Barragan, Laura F. Mendez Luque, Katrine Whiteson, Angela G. Fleischman. Specific gut microbial community is associated with specific cancer types: A strategy for cancer detection and prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5908.