Different Types Of Cancer Research Articles

The Effects of Patient-Centered Communication on Patient Engagement, Health-Related Quality of Life, Service Quality Perception and Patient Satisfaction in Patients with Cancer: A Cross-Sectional Study in Türkiye.

Patient-centered communication is a type of communication that takes place between the provider and the patient. It is aimed to reveal the effects of patient-centered communication on patient engagement, health-related quality of life, perception of service quality and patient satisfaction. The study was conducted by applying multiple regression analysis to the data obtained from 312 patients with cancer treated in a training and research hospital affiliated to the Ministry of Health in Diyarbakır, Türkiye. More than half of the patients were female and had stage 4 cancer. Different types of cancer were detected (breast cancer, cancer of the digestive organs, lymphatic and hematopoietic cancer, cancer of the genital organs, cancer of the respiratory organs, etc.). It can be stated that the average values obtained by patients from patient-centered communication and its sub-dimensions are high. There are positive, moderate and low and significant relationships between the overall patient-centered communication and patient engagement, patient satisfaction, service quality perception and quality of life. It was statistically revealed that patient-centered communication positively affected patient engagement, health-related quality of life, service quality perception, and patient satisfaction. Patient-centered communication positively affects various short and medium-term health outcomes and this study offers suggestions for improving patient-provider communication.

Biotechnological interventions for the production of forskolin, an active compound from the medicinal plant, Coleus forskohlii.

Coleus forskohlii, an Indian-origin medicinal plant is the sole natural source of the labdane terpenoid forskolin (C22H34O7), with growing demand. Forskolin emerged as an industrially important bioactive compound, with many therapeutic applications in human health. It has established potential effects in the treatment of various diseases and conditions such as glaucoma, asthma, obesity, allergies, skin conditions and cardiovascular diseases. Moreover, clinical trials against different types of cancers are progressing. The mechanism of action of forskolin mainly involves activating adenylyl cyclase and elevating cAMP, thereby regulating different cellular processes. For the extraction of forskolin, tuberous roots of C. forskohlii are used as they contain the highest concentration of this metabolite. Approximately 2500 tonnes of the plant are cultivated annually to produce a yield of 2000-2200 kg ha-1 of dry tubers. The forskolin content of the root is distributed in the range of 0.01-1%, which cannot meet the increasing commercial demands from industries such as pharmaceuticals, cosmetics, dietary supplements, food and beverages. Hence, various aspects of micropropagation with different culture methods that employ precursors or elicitors to improve the forskolin content have been explored. Different extraction and analytical methods are also introduced to examine the yield and purity of forskolin. This review discusses the significance, clinical importance, mechanism of action and different approaches used for mass production including tissue culture for the lead compound forskolin to meet market needs.

In Silico Studies on Natural Products and Derivatives Against Different Types of Cancer.

According to the World Health Organization (WHO), cancer is the second cause of death worldwide, responsible for almost 10 million deaths and accounting for one in every six deaths. It is a disease that can affect any organ or tissue with rapid progression to the final stage, which is metastasis, in which the disease spreads to different regions of the body. Many studies have been carried out to find a cure for cancer. Early diagnosis contributes to the individual achieving the cure; however, deaths are increasing considerably due to late diagnosis. Thus, this bibliographical review discussed several scientific research works pointing to in silico analyses in the proposition of new antineoplastic agents for glioblastoma, breast, colon, prostate, and lung cancer, as well as some of their respective molecular receptors involved in molecular docking simulations and molecular dynamics. This review involved articles describing the contribution of computational techniques for the development of new drugs or already existing drugs with biological activity; thus, important data were highlighted in each study, such as the techniques used, results obtained in each study, and the conclusion. Furthermore, 3D chemical structures of the molecules with the best computational response and significant interactions between the tested molecules and the PDB receptors were also presented. With this, it is expected to help new research in the fight against cancer, the creation of new antitumor drugs, and the advancement of the pharmaceutical industry and scientific knowledge about studied tumors.

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

The diagnostic potential of miR-196a-1 in colorectal cancer

BackgroundColorectal cancer (CRC) is a common malignancy worldwide. MicroRNAs (miRNAs) are important epigenetic alterations that notably impact various physiological and pathological processes by acting as negative regulators of gene expression. Furthermore, they have a vital function in different types of cancers, including CRC. In this research, we evaluated, for the very first time, the expression levels of miR-196a-1 in the tissue and plasma of patients with CRC and also homeobox D8 (HOXD8) as the target gene.Materials and methodsThis study included a collection of 220 plasma and tissue samples from 55 patients diagnosed with CRC, as well as 55 healthy individuals matched by age and sex. Total RNA was extracted from plasma and tissue samples, and then polyadenylation and cDNA synthesis were performed. The expression levels of miR-196a-1 and HOXD8 as target gene was evaluated by quantitative RT-PCR (qRT-PCR) assay. We compared the diagnostic value of plasma miR-196a-1 with that of the circulating tumor markers CA19-9 and CEA using a Receiver Operating Characteristics (ROC) analysis. The association of miR-196a-1 with clinicopathological characteristics was assessed in tissue and plasma samples from patients with CRC.ResultsOur data demonstrated that the expression levels of miR-196a-1 in the tissue and plasma samples of CRC patients were 11.426- and 11.655-fold higher, respectively than those in adjacent normal tissue and plasma samples from normal subjects (p < 0.001). Through ROC curve analysis, it was identified that the sensitivity and specificity of miR-196a-1 for tissue samples, with an AUC of 0.925, were 89% and 98%, respectively. In addition, the sensitivity and specificity for plasma samples with an AUC of 0.801 were 70% and 98%, respectively. These findings reveal that miR-196a-1 is a useful biomarker for discriminating cases from controls. Furthermore, the expression of HOXD8 was not significantly altered in tumor tissue samples compared to adjacent normal tissues (P > 0.05).ConclusionsThese results show that miR-196a-1 has an oncogenic impact and plays a significant role in CRC development. The results also indicate that miR-196a-1 could serve as a novel noninvasive biomarker for the detection of CRC.

Understanding communication between patients and healthcare professionals regarding comprehensive biomarker testing in precision oncology: A scoping review.

Precision oncology, using comprehensive biomarker testing (cBT) to inform individual cancer diagnosis, prognosis and treatment, includes increasingly complex technology and clinical data sets. People impacted by cancer (patients and caregivers) and healthcare professionals (HCPs) face distinct challenges in navigating the cBT and personalized treatment landscape. This review summarizes evidence regarding cBT-related communication between people impacted by cancer and HCPs and identifies important avenues for future research in precision oncology. A scoping review was conducted using records published in PubMed during January 2017-August 2022, focusing on the breadth of topics on patient-HCP communication and knowledge resources used by HCPs as guidance in cBT-related communication. Data were extracted from records meeting inclusion criteria, and findings were summarized according to main topics. The search identified 287 unique records and data were extracted from 42 records, including nine from expert input. Most records originated from the United States included patients with different types of cancer, and oncologists were the main HCPs. Patients' motivation for undergoing cBT and receiving results was generally high in different settings. However, patients' understanding of cBT-related concepts was limited, and their knowledge and information preferences changed based on cBT implications and significance to family members. HCPs were valued by patients as a trusted source of information. Limited evidence was available on HCPs' information-seeking behavior and factors influencing cBT-related knowledge and confidence, often self-reported as insufficient. Patient education by knowledgeable and confident HCPs, information management and a caring patient-HCP relationship communicating continuity of care regardless of cBT results are crucial to empower patients and shared decision-making in precision oncology. More data on the process and structure of cBT-related communication, distinction between and characterization of different timepoints of patient-HCP interactions are needed.

Systematic analysis of the role of LDHs subtype in pan-cancer demonstrates the importance of LDHD in the prognosis of hepatocellular carcinoma patients

BackgroundLactate dehydrogenase (LDHs) is an enzyme involved in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Given the regulatory role in the biological progression of certain tumors, we analyzed the role of LDHs in pan-cancers.MethodsCox regression, Kaplan–Meier curves, Receiver Operating Characteristic (ROC) curves, and correlation of clinical indicators in tumor patients were used to assess the prognostic significance of LDHs in pan-cancer. The TCGA, HPA, TIMER, UALCAN, TISIDB, and Cellminer databases were used to investigate the correlation between the expression of LDHs and immune subtypes, immune checkpoint genes, methylation levels, tumor mutational load, microsatellite instability, tumor-infiltrating immune cells and drug sensitivity. The cBioPortal database was also used to identify genomic abnormalities of LDHs in pan-cancer. A comprehensive assessment of the biological functions of LDHs was performed using GSEA. In vitro, HepG2 and Huh7 cells were transfected with LDHD siRNA and GFP-LDHD, the proliferation capacity of cells was examined using CCK-8, EdU, and colony formation assays; the migration and invasion of cells was detected by wound healing and transwell assays; western blotting was used to detect the levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt phosphorylation.ResultsLDHs were differentially expressed in a variety of human tumor tissues. LDHs subtypes can act as pro-oncogenes or anti-oncogenes in different types of cancer and have an impact on the prognosis of patients with tumors by influencing their clinicopathological characteristics. LDHs were differentially expressed in tumor immune subtypes and molecular subtypes. In addition, LDHs expression correlated with immune checkpoint genes, tumor mutational load, and microsatellite instability. LDHD was identified to play an important role in the prognosis of HCC patients, according to a comprehensive analysis of LDHs in pan-cancer. In HepG2 and Huh7 cells, knockdown of LDHD promoted cell proliferation, migration, and invasion, promoted the protein expression levels of MMP-2, MMP-9, N-cadherin, and Akt phosphorylation, but inhibited the protein expression level of E-cadherin. In addition, LDHD overexpression showed the opposite changes.ConclusionLDHs subtypes can be used as potential prognostic markers for certain cancers. Prognostic and immunotherapeutic analysis indicated that LDHD plays an important role in the prognosis of HCC patients. In vitro experiments revealed that LDHD can affect HCC proliferation, migration, and invasion by regulating MMPs expression and EMT via Akt signaling pathway, which provides a new perspective on the anti-cancer molecular mechanism of LDHD in HCC.

DCLK1 is Overexpressed and Associated with Immune Cell Infiltration in Hepatocellular Carcinoma.

Recent research has shown that Doublecortin-like kinase 1 (DCLK1) is overexpressed in different types of cancer. It has recently been described as a cancer stem cells (CSCs) marker, is associated with carcinogenesis, and positively correlates with infiltration of multiple immune cell types in some cancers. However, studies focused on assessing DCLK1 expression in HCC are limited, and the role of DCLK1 in HCC tumor immunity remains to be determined. In this study, we used a modified model of the resistant hepatocyte (MRHM) to evaluate DCLK1 expression in HCC. Furthermore, DCLK1 expression in HCC was analyzed using TIMER 2.0, UALCAN, GEPIA, GEO, and HPA web-based tools. Correlations between DCLK1 expression and clinicopathological factors in patients were analyzed using the UALCAN web-based tool. Finally, correlations between DCLK1 and immune infiltrates were investigated using the TIMER 2.0 and TISIDB web-based tools. The results showed that DCLK1 is significantly overexpressed during progression of the HCC carcinogenic process in the MRHM. DCLK1 is overexpressed in HCC according to multiple publics web-based tools, and its overexpression is associated with cancer stage. Furthermore, DCLK1 expression was correlated with infiltration levels of multiple immune cells, immunomodulatory factors, immunoinhibitors, MHC molecules, chemokines, receptors, and immune cell-specific markers. These results suggest that DCLK1 is a potential prognostic biomarker that determines cancer progression and correlates with immune cell infiltration in HCC.

Vitamin D and potential effects on cancers: a review.

Cancer is characterized by the abnormal and uncontrollable division and growth of cells that can infiltrate tissues and alter normal physiological function, which will become crucial and life-threatening if left untreated. Cancer can be a result of genetics, such as mutations or environmental causes, including smoking, lack of physical activity, as well as nutritional imbalance in the body. Vitamin D is one of the foremost nutrients that play a crucial role in a variety of biochemical pathways, and it is an important key factor in several diseases. Vitamin D is an essential nutrient for preventing malignancies and a complementary treatment for cancer through direct and indirect biochemical pathways. In this article, we summarized the correlation between vitamin D and various cancers using an extensive search on PubMed, Google Scholar, and Scopus. This paper reviews the role of vitamin D in different types of cancer.

Sulforaphane-A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies.

Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models. SFN has also shown antidiabetic and anti-obesity effects, improving glucose tolerance and reducing fat accumulation. SFN's ability to activate Nrf2, a transcription factor regulating oxidative stress and inflammation in cells, is a primary mechanism behind its anticancerogenic and antidiabetic effects. Its antioxidant, anti-inflammatory, and anti-apoptotic properties are also suggested to provide beneficial effects against neurodegenerative diseases. The potential health benefits of SFN have led to increased interest in its use as a dietary supplement or adjunct to chemotherapy, but there are insufficient data on its efficacy and optimal doses, as well as its safety. This review aims to present and discuss SFN's potential in treating various diseases, such as cancer, diabetes, cardiovascular diseases, obesity, and neurodegenerative diseases, focusing on its mechanisms of action. It also summarizes studies on the pharmacological and toxicological potential of SFN in in vitro and animal models and explores its protective role against toxic compounds through in vitro and animal studies.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Radiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer. The present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays. This process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC. To summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

P096 Human extrachromosomal circular DNA is an emerging biomarker in Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Diseases (IBD) are chronic multifactorial disorders, which affect the gastrointestinal tract, including Ulcerative Colitis (UC) and Crohn’s Disease (CD). The existence of extrachromosomal circular DNA fragments (eccDNA) is well established, and it arises from all parts of the genome. eccDNA has mainly been studied in the context of cancer and not in relation to other diseases, and it has become a promising diagnostic and prognostic biomarker for different types of cancer. Herein, we investigate for the first time the role of eccDNA in IBD. Methods Forty consecutive IBD patients (19 CD, 21 UC) and 13 HC were enrolled, who underwent screening colonoscopy were prospectively enrolled at our center in this observational, case-controlled study. In IBD patients, disease activity was assessed using PMS and MES for UC, and HBI and SES-CD for CD. Colonic biopsies were collected from both inflamed and healthy mucosa in IBD patients and from HC. eccDNA was enriched, sequenced, and identified with Circle Finder from intestinal biopsies. Results Colonic mucosal samples from IBD patients showed increased average of eccDNAs, across all chromosomes than samples from HC. Furthermore, there was a slight yet significant tendency for larger eccDNAs in IBDs compared to HCs. Focusing on eccDNA coming from genic elements ("genic eccDNAs"), approximately 60% were fragments from protein coding genes, 32% from non-coding RNAs and 8% from pseudogenes. IBD patients had, on average, significantly more genic eccDNAs in their intestines as compared to HC. Moreover, IBD in remission had fewer eccDNAs in their intestines than active disease, although not statistically significant. eccDNAs from phosphodiesterase genes and genes involved in lipid metabolism were enriched in patients with active IBD than patients in remission. eccDNA from inflamed mucosa (both in UC and in CD) show an enrichment of genes related to inflammatory and immune pathways, such as MAPK, mTOR, ErB, Rap-1 and cGMP (SPOKE3, GRID2, DLEU1, ITGA8, NRG1). Conclusion We are the first to uncover an IBD-specific pattern of eccDNA production. Furthermore, we identified genic hotspots which characterize active vs. inactive disease and inflamed vs. healthy colonic tissue. We propose that eccDNA identification could be a promising new diagnostic marker for IBD patients.

Synthetic Curcumin Analogs in the Treatment of Cancer: A Literature Review.

Treatment of cancer, one of the most fatal diseases in the present century, has become a topic of global concern. Unfavorable unintentional effects of chemotherapy and radiation treatments have been the main reasons for the research on the discovery of drugs with a broader spectrum of effectiveness and efficiency, with minimal side effects. Curcumin (diferuloylmethane) is a naturally occurring phenolic structure with anticancer properties through its inhibition of cell multiplication, metastasis, and prolongation of cell cycle suppression of apoptosis in various tumor cells. The primary restriction regarding the use of curcumin in cancer treatment is related to poor bioavailability and unfavorable pharmacokinetic profiles of curcumin due to its poor absorption rate, fast metabolism, and systemic elimination. A variety of ways have been proposed to overcome these limitations. With this background, the present study focuses on providing a comprehensive overview of the anticancer properties of curcumin derivatives and the synthesis of curcumin analogs with application to different types of cancers. The regulation of various target and signaling pathways is considered in various cancers, including breast, gastrointestinal, pancreatic, prostate, skin, and lung cancers. A review of the literature indicates that modifying the structure of curcumin through the substitution of the phenyl group and unsaturated carbon branch around the two main sites of oxygen can result in the improvement of physical and chemical properties, as well as the enhancement of physiological activities of the curcumin molecule and the anti-cancer activities of this polyphenol. Curcumin analogs demonstrate anticancer properties at multiple targets at different cell stages and by various signaling biochemical pathways. These include cytokines, transcription factors, growth factors, and modulation of genes involved in cellular proliferation and apoptosis in breast, gastrointestinal, skin, prostate, and lung cancers, thereby mitigating tumor progression.

Expression heterogeneity, tumor immune characteristics and the prognosis effects of OPRL1 in patients with tumors: a pan-cancer study combined with bioinformation analyses and in vitro validation

PurposeOpioids are currently the most frequently prescribed analgesics in clinical practice. However, their effect on cancer progression remains a topic of debate. Opioid receptors (ORs) are present in various types of tumor cells and their expression levels vary depending on the type of tumor. This study aims to explore and preliminarily characterize the association between four different ORs (μ, δ, κ, and nociception/orphanin FQ peptide receptor) and the prognosis of different types of tumors for comparison, with a focus on nociception/ orphanin FQ peptide receptor.MethodsThe expression levels of four ORs in normal tissues and immune cells were obtained from Human Protein Atlas (HPA) RNA-seq dataset, Monaco dataset, and Consensus dataset. Pan-cancer analysis was performed using the The Cancer Genome Atlas (TCGA) dataset, which included the expression of four ORs in different cancer types, significant copy-number alterations (sCNA), gene mutations of the four ORs, survival analysis, co-expression genes analysis, functional enrichment analyses, and correlations between ORs and immune cell infiltration levels. Based on the results of bioinformatic analysis, we selected 10 cancer cell lines for validation in vitro using specific agonists for the four ORs.ResultsOPRL1 (opioid related nociceptin receptor 1 gene) exhibited the highest abundance across different types of cancers, while OPRM1 (opioid receptor mu 1 gene) and OPRD1 (opioid receptor delta 1 gene) were barely detectable in multiple cancer types. Pan-cancer survival analysis revealed the overall worse/better prognosis of the four ORs in certain cancer types. Elevated levels of OPRM1 appear to be associated with poorer outcomes in breast invasive carcinoma and kidney renal clear cell carcinoma. Elevated OPRD1 levels are connected to worsen outcomes in kidney renal clear cell carcinoma and liver hepatocellular carcinoma, but better prognosis in bladder urothelial carcinoma. Increased OPRK1 (opioid receptor kappa 1 gene) expression is linked to a poorer prognosis in kidney renal papillary cell carcinoma. Furthermore, high OPRL1 expression relates to worse outcomes in bladder urothelial carcinoma and liver hepatocellular carcinoma, but better outcomes in breast invasive carcinoma and pancreatic adenocarcinoma. Functional enrichment analyses found that immune-related pathways were enriched in OPRK1 and OPRL1, with OPRL1 exhibiting the highest correlation with immune cell infiltration. Different effects on cell growth, migration, and invasion were observed in different cancer types upon the administration of agonists for the four ORs.ConclusionOPRL1 may play a vital role in monocytes and regulating the immune response and tumor-infiltrating macrophages. Due to its high abundance in different types of tumors, it may hold greater clinical significance for oncology patients. OPRK1 also participates in immune-related pathways. OPRL1 could potentially serve as therapeutic targets for different types of cancers.Graphical

Genomic characterization of unresectable/recurrent early-onset gastric cancer by comprehensive genomic profiling tests.

393 Background: The incidence of early-onset gastric cancer (EOGC: age ≤45 years) is showing an increasing trend. Although EOGC has unique clinicopathological features compared with late-onset gastric cancer (LOGC: age&gt;45 years), disparities in genetic alterations (GAs) between EOGC and LOGC are not fully understood in patients with unresectable/recurrent GC. We aim to investigate to elucidate unique GAs in unresectable/recurrent EOGC. Methods: We retrospectively reviewed data on patients with unresectable/recurrent GC who underwent comprehensive genomic profiling (CGP) tests and were registered as “Stomach adenocarcinoma (STAD)” cases in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan from June 2019 to April 2023. CGP tests were conducted by NCC Oncopanel System (NOP) or FoundationOne CDx (F1). We examined somatic GAs, microsatellite instability (MSI) status, and tumor mutation burden (TMB) of GC. TMB-high was defined as ≥10 mutations/Mb. Actionable GAs were counted if they were classified as “pathogenic/oncogenic” or “likely pathogenic/likely oncogenic variants”. Druggable GAs are actionable GAs that can be treated with drugs approved for GC or other types of cancer or have shown efficacy in clinical trials for either GC or different types of cancer. Results: In total,112 patients with EOGC and 810 patients with LOGC were identified. In EOGC group, most common actionable GAs included TP53 (59.8%), ARID1A (17.0%), KRAS (15.2%), CDKN2A (11.6%), FGFR2 (11.6%), and CDH1 (9.8%). Compared to the LOGC group, the EOGC group exhibited a significantly higher frequency of actionable GAs in FGFR2(11.6% vs. 4.6%, P=0.0059), CDH1 (9.8% vs. 4.1%, P=0.015) and BAP1 (3.6% vs. 0.6%, P=0.016). On the other hand, the EOGC group showed a significantly lower frequency of actionable GAs in ERBB2(7.1% vs. 20.1%, P=0.0004), CCNE1 (4.5% vs. 19.0%, P=0.0001), and AURKA (0% vs. 7.9%, P=0.0003) compared with the LOGC group. In the EOGC group compared to the LOGC group, the proportions of MSI-high were 0.9% vs. 2.6% (P=0.345), and those of TMB-high were 4.5% vs. 11.6% (P=0.011). Excluding ERBB2 amplification, druggable GAs in the ECOG group included FGFR2 amplification (9.8%), MET amplification (4.5%), EGFR amplification (1.8%), KRAS G12C mutation (1.8%), and MDM2 amplification (0.9%). Conclusions: Among unresectable/recurrent GC population, EOCG has displayed distinct genetic profiles of GAs compared to LOGC. CGP tests may be useful in expanding treatment opportunities for patients with unresectable/recurrent EOGC.

Comprehensive genomic profiling of advanced anal adenocarcinoma.

4 Background: Anal adenocarcinoma (anal AD) is a rare and aggressive gastrointestinal malignancy. Because of its rarity, no standard therapy is established and treatment strategy for advanced rectal adenocarcinoma (rectal AD) is extrapolated. Little is known for genetic alterations (GAs) and their therapeutic implications in advanced anal AD. We aim to investigate to clarify genomic profiles of advanced anal AD in comparison of advanced rectal AD. Methods: We retrospectively extracted data on patients with advanced anal AD and advanced rectal AD who underwent comprehensive genomic profiling (CGP) tests and were registered for the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. CGP tests were performed by NCC Oncopanel or FoundationOne CDx. We examined somatic GAs, microsatellite instability (MSI) status, and tumor mutation burden (TMB). TMB-high was defined as ≥10 mutations/Mb. Actionable GAs were counted if they were classified as “pathogenic/oncogenic” or “likely pathogenic/likely oncogenic” variants. Druggable GAs are actionable GAs with approved drugs for anal AD or other types of cancer or clinical trials showing efficacy for either anal AD or different types of cancer. Results: From June 2019 to April 2023, 45 patients with anal AD and 1915 patients with rectal AD were enrolled into the C-CAT database. In the anal AD group, most common actionable GAs were TP53 (89%), KRAS (51%), ERBB3 (22%), MYC (20%), SMAD4 (20%), and ERBB2 (11%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of actionable GAs in ERBB3 (22% vs. 2%, p &lt; 0.01), MYC (20% vs. 8%, p &lt; 0.01), and BRCA2 (7% vs. 1%, p &lt; 0.01), and a significantly lower frequency of actionable GAs in APC (7% vs. 85%, p &lt; 0.01). The proportion of MSI-high and TMB-high in the anal AD group and the rectal AD group were 0% vs. 0.2% (p = 0.79), and 7% vs. 5% (p = 0.54). Common druggable GAs in anal ADs included KRAS G12D mutation (22%), ERBB2 amplification (7%), BRCA2 mutation (7%), BRAF V600E mutation (2%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of druggable GAs in BRCA2 mutation (7% vs. 1%, p &lt; 0.01). Conclusions: The present study showed that anal AD had a different profile of GAs compared with advanced rectal AD. CGP tests are useful tool for identifying druggable GAs in advanced anal AD for expanding therapeutic opportunities.

Unveiling the potential anti-cancer activity of calycosin against multivarious cancers with molecular insights: A promising frontier in cancer research.

Calycosin may be a potential candidate regarding chemotherapeutic agent, because already some studies against multivarious cancer have been made with this natural compound. This review elucidated a brief overview of previous studies on calycosin potential effects on various cancers and its potential mechanism of action. Data retrieved by systematic searches of Google Scholar, PubMed, Science Direct, Web of Science, and Scopus by using keywords including calycosin, cancer types, anti-cancer mechanism, synergistic, and pharmacokinetic and commonly used tools are BioRender, ChemDraw Professional 16.0, and ADMETlab 2.0. Based on our review, calycosin is available in nature and effective against around 15 different types of cancer. Generally, the anti-cancer mechanism of this compound is mediated through a variety of processes, including regulation of apoptotic pathways, cell cycle, angiogenesis and metastasis, oncogenes, enzymatic pathways, and signal transduction process. These study conducted in various study models, including in silico, invitro, preclinical and clinical models. The molecular framework behind the anti-cancer effect is targeting some oncogenic and therapeutic proteins and multiple signaling cascades. Therapies based on nano-formulated calycosin may make excellent nanocarriers for the delivery of this compound to targeted tissue as well as particular organ. This natural compound becomes very effective when combined with other natural compounds and some standard drugs. Moreover, proper use of this compound can reverse resistance to existing anti-cancer drugs through a variety of strategies. Calycosin showed better pharmacokinetic properties with less toxicity in human bodies. Calycosin exhibits excellent potential as a therapeutic drug against several cancer types and should be consumed until standard chemotherapeutics are available in pharma markets.

Therapeutic effect and potential application of scorpion venom peptide

Scorpions has been existing on earth for hundreds of million years, and its venoms are mostly highly toxic and presents a deadly threat to people around the world. Scorpion venoms are highly complicated cocktails of bioactive components including proteins, amino acids, peptides, and other organic or inorganic molecules. Among them, the main active components are bioactive peptides called neurotoxins. Advancements in research on the toxic mechanisms of common scorpion toxins has found various therapeutic properties of several peptides on a large variety of diseases including different types of cancer and infections. Therefore, scorpion venoms may not only be a threat, but also a valuable source of novel drug components, especially therapeutic peptides. This research gives a brief introduction on scorpions and the components of its venoms, and focuses on presenting current knowledge on the medical effects of neurotoxins in scorpion venom, and potentials applications of the peptides in drug development.

Evaluation of artificial neural network and adaptive-network-based fuzzy inference system for ovarian and lung cancer prediction

Aims: Every year, a significant number of individuals lose their lives due to cancer or undergo challenging treatments. Indeed, the development of an effective cancer prediction method holds great importance in the field of healthcare. Methods: Machine learning methods have played a significant role in advancing cancer prediction models. In this context, this study focuses on exploring the potential of two machine learning methods: Artificial neural network (ANN) and adaptive-network-based fuzzy inference system (ANFIS) for cancer prediction. In this study, two different types of cancer, ovarian cancer and lung cancer, are taken into consideration. For the prediction of ovarian cancer, three specific biomarkers, namely human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA-125), and carcinoembryonic antigen (CEA), are used to develop a prediction model. For the prediction of lung cancer, six different variables are utilized in the development of both the ANN and ANFIS methods. Results: The findings demonstrated that the proposed methods had an accuracy rate of at least 93.9% in predicting ovarian cancer. With an accuracy rate of at least 89%, the proposed methods predicted lung cancer. Also, the proposed ANN method outperforms the ANFIS method in terms of predictive accuracy for both ovarian cancer and lung cancer. Conclusion: This study suggests that the ANN method provides more reliable and accurate predictions for these specific cancer types based on the chosen variables or biomarkers. This study highlights the potential of machine learning methods, particularly ANN, in improving cancer prediction models and aiding in the early detection and effective management of ovarian and lung cancers.

Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma.

Renal Cell Carcinoma (RCC) is the most common type of kidney cancer (85%). 75% of the RCC cases involve conventional clear cell RCC (ccRCC). Approximately, 39% of late-stage patients (stage IV) are treated with chemotherapeutic agents. Phosphatidylinositol-3-kinase (PI3K) and Mitogen-Activated Protein Kinase Kinase (MEK)/extracellular signal-regulated kinase (ERK1/2) pathways are frequently activated in RCC. In addition, atypical PKCs (PKC-ί and PKC ζ) are overexpressed in most cancer cells, and they play a central role in tumor progression and the metastasis of different types of cancers. Our goal is to establish the role of aPKCs in the regulation of multiple key activated pathways in ccRCC. In this study, we also established a novel therapeutic regimen for dual inhibition of key activated pathways. In this study, 786-0 and Caki-1 cells were studied and subjected to cell viability assay, western blot analysis, scratch & wound healing assay, transwell invasion assay, immunofluorescence, immunoprecipitation, flow cytometry, and quantitative real-time polymerase chain reaction. We used combination of PI3K inhibitor- Alpelisib (BYL719) and ICA-1 (a PKC-ι-specific 5-amino-1-2,3-dihydroxy-4-(methylcyclopentyl)-1H-imidazole-4-carboxamide). In addition to drug treatment, small interfering RNA (siRNA) technology was used to further confirm the experimental outcome of the drug treatment. Our results suggest that treatment of ccRCC cells with a combination of ICA-1 (aPKC inhibitor) and BYL719 (PI3K inhibitor) downregulates PKC-ί and causes downstream inhibition of c-Myc. Inhibition of the PKCί also reduces activation of MEK/ERK1/2. It is observed that treatment with ICA-1 disrupts the level of the aPKC-Akt1 association. ICA-1 treatment also shows a reduced level of association between aPKC and c-Myc. The inhibition of aPKCs and downstream effector proteins by combination therapy is more pronounced compared to a single therapy. These effects contribute to reduced cell growth, and eventually, the induction of apoptosis. The decreased level of N-cadherin, p-vimentin, and vimentin and the increased level of E-cadherin confirm reduced malignancy. Therefore, implementing a combination of Alpelisib and a PKC-ι inhibitor is an effective approach to reducing cell proliferation, and invasion that eventually induces apoptosis and may be considered as a potential therapeutic option in ccRCC.