Advanced Stage Research Articles

Double-protein-loaded 3D-printed polyetheretherketone cage for promoting interbody fusion via osteogenic differentiation

Intervertebral disc degeneration (IDD) is a common condition characterized by age-related wear and tear of the spine. In advanced stages or severe cases of IDD, surgical treatment involving the implantation of an interbody cage is often the primary treatment approach. Polyetheretherketone (PEEK) has been widely used in orthopedic and spinal implants due to its remarkable mechanical properties, biocompatibility, and corrosion resistance. However, when used in interbody cages, PEEK exhibits poor processability and biological inertness, which are significant disadvantages that need to be addressed. In this work, we first fabricated the PEEK cage via the fused deposition modeling (FDM) method. To improve its fusion effect, bone morphogenetic protein 2 (BMP2) was loaded onto sulfonated PEEK and sealed with gelatin/chitosan (Gel/Chi) multilayer films. Substance P was then grafted on the surface with a Schiff base. When the cage is implanted, substance P is released first, recruiting bone marrow-mesenchymal stem cells (MSCs) to the implant surface. Subsequently, upon degradation of the Gel/Chi multilayer films, BMP2 is slowly released and promotes osteogenic differentiation of MSCs. In vivo results revealed that the double-protein-loaded PEEK cage exhibited remarkable fusion effects. This work provides a novel approach for the design and fabrication of a PEEK intervertebral fusion device with an excellent fusion effect.

Multi-Dimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer.

Colorectal cancer (CRC) is frequently diagnosed in advanced stages, highlighting the need for developing approaches for early detection. Liquid biopsy using cell-free DNA (cfDNA) fragmentomics is a promising approach, but the clinical application is hindered by complexity and cost. This study aimed to develop an integrated model using cfDNA fragmentomics for accurate, cost-effective early-stage CRC detection. Plasma cfDNA was extracted and sequenced from a training cohort of 360 participants, including 176 CRC patients and 184 healthy controls. An ensemble stacked model comprising five machine learning models was employed to distinguish CRC patients from healthy controls using five cfDNA fragmentomic features. The model was validated in an independent cohort of 236 participants (117 CRC patients and 119 controls) and a prospective cohort of 242 participants (129 CRC patients and 113 controls). The ensemble stacked model showed remarkable discriminatory power between CRC patients and controls, outperforming all base models and achieving a high area under the ROC curve (AUC) of 0.986 in the validation cohort. It reached 94.88% sensitivity and 98% specificity for detecting CRC in the validation cohort, with sensitivity increasing as cancer progressed. The model also demonstrated consistently high accuracy in within-run and between-run tests and across various conditions in healthy individuals. In the prospective cohort, it achieved 91.47% sensitivity and 95.58% specificity. This integrated model capitalizes on the multiplex nature of cfDNA fragmentomics to achieve high sensitivity and robustness, offering significant promise for early CRC detection and broad patient benefit.

Retained PAX2 expression associated with DNA mismatch repair deficiency in endometrial endometrioid adenocarcinoma.

Loss of expression of tumour suppressor PAX2 and MMR deficiency (dMMR) has been frequently seen in endometrial endometrioid adenocarcinoma (EEC). However, the relationship between PAX2 expression and MMR status is unknown. We studied the PAX2 expression and examined its association with MMR status at the protein and genetic levels in 180 cases of EEC. Overall, total loss of PAX2 expression was found in about 70%, while retained PAX2 expression was seen in 30% of EEC. Among 125 cases with loss of PAX2, 68.8% were found in EECs with pMMR, while 31.2% were seen in those with dMMR. Among 55 cases of EECs with retained PAX2 expression, 92.7% were EECs with dMMR and 7.3% were those with pMMR (P < 0.001). While dMMR cases with MLH1 hypermethylation show almost equal retained or loss of PAX2 expression (52% versus 48%), dMMR with genetic alterations had significantly more retained PAX2 expression than loss of PAX2 (92.3% versus 7.7%), regardless of somatic or germline mutations. Loss of PAX2 was observed in 97.3% of dMMR with MLH1 hypermethylation compared to 2.7% of dMMR with genetic alterations (P < 0.001). Aggressive features such as higher tumour grades (FIGO 2-3) and advanced clinical stage (T2-T4) were significantly more frequently seen in dMMR with retained PAX2 expression, compared those to pMMR with loss of PAX2 expression. Our study demonstrates a close correlation between retained PAX2 expression and dMMR in EEC. The molecular mechanism and clinical significance linking these two pathways in EEC remains to be unravelled.

Design of New Aromatic Tertiary Amine-based as Butyrylcholinesterase Inhibitors Relying on Molecular Docking, ADME-Tox and Molecular Dynamics.

Butyrylcholinesterase (BChE) plays a pivotal role in the progression of Alzheimer's disease. Empirical research demonstrated a fundamental alteration in the role of BChE concerning the reduction of cholinergic neurotransmission within the brains of individuals at advanced stages of Alzheimer's. This study focuses on developing potent inhibitors for Butyrylcholinesterase (BChE) in the context of Alzheimer's disease (AD) treatment. Building upon previous research, a series of 44 aromatic tertiary amine-based compounds was investigated. Starting with ADME-Tox studies, the pharmacokinetic and pharmacodynamic properties of the compounds were analyzed to select promising candidates for BChE inhibition, which is a crucial factor in AD pathology. Molecular docking analyses identified compound M18 as the most promising candidate, and further compounds (X9 and X10) were proposed based on M18's chemical structure. These compounds displayed superior properties in terms of binding energies and hydrogen bonds in comparison to M18. The Molecular Dynamics (MD) simulations, which are over a 500 ns timeframe, confirmed the conformational stability of compounds X9 and X10, compared to M18. Overall, the stated results suggest that the proposed compounds, including X9 and X10 specifically, have a significant potential as candidates for BChE inhibition. This presents a promising avenue for therapeutic intervention in Alzheimer's disease.

Demographic profile of head and neck cancer patients: a single tertiary institution-based study in Telangana

Background: Head and neck cancer (HNC) is a broad category of cancerous entity that arise from different types of tissues and organ sites located in the topographical areas of the head and neck (Hand N). H and N squamous cell carcinomas (HNSCC) comprises 30% of all cancer cases in India. The risk factors for HNSCC include tobacco and alcohol consumption. Methods: This study aimed to determine the demographics of HNC patients and classify the incidence of H&amp;N cancers according to the primary histological type and organ of origin along with any recent change in pattern compared with previous study. Results: Highest incidence seen in 41-50 years of age group with majority of cases belonging to urban area. Tobacco chewing was observed as most common habit. Buccal mucosa cancer was seen as most common cancer particularly at gingivo-buccal sulcus. Squamous cell carcinoma was the most common type identified on histopathology. Majority of the cancers presented in locally advanced stage. Conclusions: Male plurality of carcinoma noted indicating male being more likely to be engaged in behaviours increasing risk of carcinoma head and neck. Buccal muscosa carcinoma particularly at gingivo-buccal sulcus noted to be most common site correlating to tobacco chewing habit and keeping tobacco quid at gingivo-buccal sulcus leading to prolonged exposure.

Cancer and immune response: The role of PD-1/PD-L1 checkpoint in laryngeal carcinoma. Preliminary results.

The overall survival of laryngeal squamous cell carcinoma (LSCC) hasn't changed significantly in the last decades, leading to a negative prognosis in advanced stages. So, the immunotherapy takes space with the inhibition of PD-1/PD-L1 checkpoint, involved in suppression of immune response. A prospective study was conducted on LSCC patients, selected according to strict criteria. The study was approved by the ethics committee of our Hospital. Parameters were: sex, age, smoking and alcohol habits, C-reactive protein (CRP) level in the serum, laryngeal subsite involved, differentiation-based histopathologic grading of tumor, neck node involvement, tumor stage, expression levels of PD-L1 (as Combined Positive Score - CPS). P-value < 0.05 was statistically significant. 58 patients were included: 31.03% were females, mean age 63.55±10.09. A statistically significant correlation between CPS and smoking habits and N stage was found. CRP resulted increased in 44.83% of patients with a statistically significant correlation with CPS. The most cases were glottic cancers (46.55%). 75.86% of tumors were moderately-differentiated, without correlation with CPS. PD-L1 expression levels are variables independent of sex, age, alcohol consumption, differentiation degree of LSCC. A statistically significant correlation between PD-L1 expression levels and smoking habits, neck node status and CRP was found. This last finding demonstrates the involvement of PD-1/PD-L1 checkpoint in immune response in case of cancer. However, these results need further studies to detect the best patients tailored for treatment with anti-PD-1/PD-L1 blocking antibodies.

Soil morphological characteristics in the active volcanic toposequence zone at Tangkuban Parahu volcano, Indonesia

Soil formation in volcanic terrains presents a significant challenge due to the diverse physical and chemical properties imparted by volcanic activity, which are not yet fully understood. This study investigates the unique morphological characteristics of soil profiles within crater topography sequences at the Tangkuban Parahu Volcano, Indonesia. To address this gap, five representative sample profiles (I, II, III, IV, V) were analyzed. The Ratu Crater pathway topography was characterized by steep to very steep slopes. Detailed analysis identified three predominant soil layers, each with distinct features such as color, texture, porosity, and chemical composition, reflecting different stages of soil formation. At the highest elevation near the crater rim, Profile V was composed mainly of volcanic ash, with a loose structure, high porosity, and acidic pH, indicative of recent volcanic deposits. Profile III, at intermediate elevations, consisted of highly weathered soil with sandy loam textures and clear layer demarcations, suggesting prolonged soil development and consolidation. Profile I, at the lowest elevation, featured loamy sand with significant weathering and organic matter incorporation, indicating advanced soil development stages. The findings underscore the impact of volcanic activity on soil morphology, revealing distinct layers that correlate with various ages and developmental stages. Understanding these processes can inform agricultural practices.

Pulsatillic acid as a potential inhibitor of protein kinase C-alpha in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a global health concern with a significant impact on morbidity and mortality. Small molecule inhibitors targeting genetic mutations like EGFR and ALK have shown promise in NSCLC treatment. This study focuses on Protein Kinase C-alpha (PKCα), implicated in NSCLC pathogenesis. Overexpression of PKCα correlates with advanced disease stages. Preclinical studies suggest its inhibition can suppress NSCLC cell growth. The research employs molecular docking to identify Pulsatillic acid (PA) as a potential PKCα inhibitor. ADMET predictions support PA's candidacy and PASS analysis and Swiss Target Prediction reveal its biological properties. Fluorescence-based binding assays demonstrate PA's inhibitory potency on PKCα, aligning with molecular docking findings. Cytotoxicity assays show PA's minimal impact on HEK-293 cell viability, with an IC50 of 21.03 μM in A549 cells. mRNA expression analysis in A549 cells indicates PA's potential inhibitory effect on PKCα. In conclusion, this study highlights that PA may emerge as a promising therapeutic candidate for NSCLC, emphasizing the need for further research, validation, and exploration of its translational potential. The study contributes valuable insights into NSCLC treatment strategies, emphasizing the significance of targeting PKCα.

Expression and prognostic analysis of PFKFB4 in oral squamous cell carcinoma.

Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.

‘Plasma first’ approach for detecting epidermal growth factor receptor mutation in advanced non-small cell lung carcinoma

IntroductionThe treatment approach for recently diagnosed advanced non-small cell lung cancer (NSCLC) with EGFR mutations primarily relies on confirming the tissue diagnosis as non-squamous NSCLC. This routine clinical practice of tissue diagnosis imposes several barriers and delays in turnaround time (TAT) for biomarker testing, significantly delaying the time to treatment. The objective of this study is to investigate the ‘plasma first’ approach for detection of EGFR mutation in advanced stage treatment naïve NSCLC patients.MethodsWe prospectively collected blood samples of treatment naïve patients with clinical and radiological suspicion of advanced stage NSCLC prior to obtaining tissue biopsy. Plasma cfDNA was tested for EGFR mutation using two different methods. We compared the sensitivity and TAT of liquid biopsy with tissue biopsy.ResultsIn total, we analyzed plasma cell-free DNA (cfDNA) of 236 patients suspected of having advanced NSCLC for EGFR mutations. We observed a notably shorter turnaround time (TAT) of 3 days, which was significantly quicker compared to the 12-day TAT for tissue biopsy (p < 0.05). The ddPCR method had a sensitivity of 82.8%, which was higher than 66.34% sensitivity of ARMS-PCR. The current study also highlights that there is no significant difference in the clinical outcome of the patients whether treated based on liquid biopsy only or tissue biopsy (median progression-free survival of 11.56 vs. 11.9 months; p = 0.94).ConclusionsUtilizing a ‘plasma first’ strategy, given its shorter turnaround time, strong positive concordance and comparable outcomes to tissue biopsy, emerges as a highly specific and reliable method for detecting EGFR mutations in advanced-stage NSCLC.

Diet at birth is critical for healthy growth, independent of effects on the gut microbiota

BackgroundColostrum is the first milk for a newborn. Its high content in microbiota shaping compounds and its intake at the time of gut microbiota seeding suggests colostrum may be critical in the establishment of a healthy microbiota. There is also accumulating evidence on the importance of the gut microbiota for healthy growth. Here, we aimed to investigate the contribution of colostrum, and colostrum-induced microbiota to growth promotion. Addressing this question is highly significant because (1) globally, less than half of the newborns are fully colostrum fed (2) the evidence for the importance of the microbiota for the prevention of undernutrition has only been demonstrated in juvenile or adult pre-clinical models while stunting already starts before weaning.ResultsTo address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota.ConclusionOur data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum’s bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting.98mWSFedBqCALfgBr5hPfAVideo

Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers.

The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients.

Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial.

To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

The clinical prognostic significance of miR-140–5p expression in patients with cancer: A Meta and Bioinformatic analysis

The prognostic value of microRNA-140–5p (miR-140–5p) expression in cancer patients has been investigated, but with inconsistent results. This meta-analysis aims to determine the prognostic significance of miR-140–5p expression in patients with various malignancies. A comprehensive literature search was conducted using PubMed, Web of Science, ProQuest, Cochrane, and Google Scholar to identify relevant studies published before June 2023. Pooled hazard ratios (HR) and odds ratios (OR) with 95 % confidence intervals (CI) were calculated to assess the prognostic importance and clinicopathological features of miR-140–5p in overall survival (OS) and disease-free survival (DFS) of cancer patients, respectively. The CancerMIRNome database and other OS analysis webservers were utilized to explore the prognostic value and expression profile of miR-140–5p. A total of 17 studies were included in the final analysis. The results demonstrated that decreased miR-140–5p expression was significantly associated with inferior OS (pooled HR 0.63; 95 % CI, 0.51–0.79; p < 0.001) and DFS (pooled HR 0.40; 95 % CI, 0.25–0.64; p < 0.001). Pooled ORs indicated a significant correlation between reduced miR-140–5p expression and positive lymph node metastasis (LNM; OR = 3.42; 95 % CI, 2.36–4.94; p < 0.001), advanced tumor stage (OR = 2.80; 95 % CI, 2.07–3.78; p < 0.001), and positive distant metastasis (DM; OR = 10.81; 95 % CI, 3.31–35.30; p < 0.001). No significant associations were observed between miR-140–5p expression and gender (OR = 0.94; 95 % CI, 0.70–1.28; p = 0.70), age (OR = 1.31; 95 % CI, 0.99–1.74; p = 0.06), tumor size (OR = 1.55; 95 % CI, 0.77–3.10; p = 0.22), and histological grade (OR = 1.20; 95 % CI, 0.46–3.10; p = 0.71). Subgroup analyses revealed that decreased miR-140–5p expression was associated with shorter OS in subgroups based on sample size (<100 or >100), tumor origin (GI or non-GI), and cancer type (GC/CRC). Bioinformatic analysis supported the finding that miR-140–5p was downregulated in most tumor tissues, and its reduced expression was linked to poor prognosis in patients with multiple malignancies. The prognostic significance of miR-140–5p in predicting reduced OS and DFS suggests that measuring miR-140–5p expression levels before treatment could serve as a valuable biomarker for identifying cancer patients with an unfavorable prognosis and improving clinical management.

Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments

ObjectiveCirculating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).DesignWe analysed 772 plasmas from 173...

The prognostic role of mitosis index, stage and grade of endometrial cancer in Dr. Soetomo General Academic Hospital Surabaya, Indonesia, in 2018-2020

HIGHLIGHTS 1. Mitotic index and grade are prognostic factors for endometrial cancer, but both are independent.2. Stage and mitotic index associated with cell proliferation affect the prognosis of endometrial cancer. ABSTRACT Objective: This study aimed to analyze the correlation between the mitotic index and the stage and grade of endometrial cancer. Materials and Methods: We collected pathology reports of endometrial cancer from the Pathology Laboratory at Dr. Soetomo General Hospital in Surabaya, Indonesia, covering cases diagnosed between 2018 and 2020. A total of 106 cases of endometrial cancer were included in this study. For each case, detailed records of the cancer stage, grade, and mitotic index were recorded. The mitotic index, an indicator of cell proliferation, was quantified, and its correlation with cancer stage and grade was assessed. To determine the strength and direction of these relationships, we performed a Spearman rank correlation statistical analysis for non-parametric data. Results: Our findings indicated a significant positive correlation between the mitotic index and the stage of endometrial cancer. An increase in the mitotic index, reflecting a higher proliferation rate of cancer cells, was associated with a more advanced cancer stage, suggesting that the mitotic index could potentially serve as a prognostic marker for assessing tumor progression in endometrial cancer. However, our analysis revealed no significant correlation between the mitotic index and the histological grade of endometrial cancer, implying that the grade, which typically reflects the differentiation status and morphological characteristics of the tumor cells, is independent of the proliferation rate as measured by the mitotic index. Conclusion: The mitotic index is positively correlated with the stage of endometrial cancer but does not show a correlation with the histological grade. These findings highlight the potential use of the mitotic index in staging endometrial cancer.

A stitch in time: revolutionizing cancer care in Pakistan

Madam, Pakistan is a developing country in South Asia with a young population. According to the International Agency for Research on Cancer, more than 178,000 new cancer patients are diagnosed in Pakistan each year, and the number of people that die from cancer is more than 117,000 per annum. [1]. Most cancer patients in Pakistan present when they are in the advanced stage of their disease. It makes it far more difficult to help the patients rendering efforts at complete cure futile.[1]. One of the leading causes of late identification of cancer is a lack of awareness of cancer as a possible diagnosis, even among physicians, followed by poverty and a lack of basic education and facilities. Pakistan, being a developing country, is facing cancer treatment as a major issue. There are less than 40 hospitals nationwide that claim to provide cancer treatment and facilities for cancer patients [1]. The lack of formal cancer referral channels in Pakistan's health system is a serious problem. This means that patients with suspected cancer may not receive timely diagnosis and treatment. Therefore, it is necessary to introduce a referral pathway like the one used by NICE (National Institute of Health and Care Excellence) for suspected cancer recognition and referral as shown in figure 1 [2]. The importance of cancer referral pathways lies in their ability to facilitate early diagnosis of cancer. Early diagnosis is critical for improving patient outcomes and increasing survival rates. A cohort study on the English urgent referral pathway identified a subgroup of 37% of patients with a low propensity to use urgent referral. Patients with these practices had 7% higher mortality rate compared to the patients having access to urgent cancer referrals. The absolute difference in cumulative mortality was about 5% to 6% in the risk of death four years after the diagnosis of cancer [3]. In the United Kingdom, a formal cancer referral pathway has been put in place to guarantee that patients with suspected cancer receive prompt diagnoses and treatments. Guidelines for referral of suspected cancer have been issued by the National Institute for Health and Care Excellence (NICE). [4] It describes proper primary care investigations and whom to refer for a specialist's opinion. It attempts to inform people about what to anticipate if they experience symptoms that could be cancer.[4] Unfortunately, in Third World countries like Pakistan, there is no such formal pathway. ---Continue

Syndecan-4 levels in bronchoalveolar lavage fluid and serum in non-small cell lung cancer

BACKGROUND Lung cancer has the highest cancer-related mortality rate worldwide. Research has been conducted to improve early detection and markers of predictive value but only focused on the expression of syndecan-4 (SDC4) in serum. Studies in bronchoalveolar lavage (BAL) fluids of non-small cell lung cancer (NSCLC) patients are still limited. This study aimed to evaluate the clinical value of SDC4 in serum and BAL in NSCLC patients. METHODS Blood serum and BAL fluids were obtained from 44 patients with NSCLC and 41 non-cancer patients as the control. The level of SDC4 was measured. The relationships between SDC4 and clinicopathologic factors were also analyzed. RESULTS Serum SDC4 levels in NSCLC patients were significantly lower than the control group (p = 0.002). Furthermore, the disease stages and serum SDC4 levels had a negative correlation, which was lower in the advanced stage (IIIb/IV) than in the initial stage (I/II/IIIa) (p = 0.517). The same results were obtained from BAL fluids SDC4 levels, which were significantly lower in the advanced stage (IIIb/IV) than in the early stage (I/II/IIIa) (p = 0.007). CONCLUSIONS Serum SDC4 levels in NSCLC patients were lower than those of non-cancer patients. They also performed different results in disease stages. SDC4 could be a helpful biomarker in NSCLC.

Evaluation of Micro-RNA Expression Profiling Level as Biomarkers for Diagnosis and Gene Sequencing in Patients Suffering from Breast Cancer

Background: Human bloodstream microRNAs (miRNAs) have emerged as a promising predictive and diagnostic biomarker for a range of cancers, including breast cancer. Our objective was to look into new miRNA biomarkers for diagnosis in the serum of patients with breast cancer and track the expression levels at different stages using miRNA profiling.Methods: 53 breast cancer patients and 10 healthy controls had blood samples tested for three miRNAs. miRNAs were extracted from blood and evaluated using real-time quantitative polymerase chain reaction. After extracting genomic DNA, miRNA primer-produced PCR products were sequenced to discover point mutations that may contribute to the illness.Results: After examining miR195, miR200b, and miR331, breast cancer patients had a significantly lower miR195 level than healthy persons. In addition, miR200b expression levels were significantly lower in breast cancer patients than in healthy individuals. In advanced stages, miR331 expression was substantially higher than in healthy people.Conclusion: The findings of our study demonstrated a significant association between the expression of miRNAs and the prognosis of breast cancer. Additional research is necessary to study better the correlation between these circulating miRNAs and the stages of breast cancer.Keywords: Breast cancer; Circulating miRNAs; miR195; miR200b; miR331 RT PCR; Gene Sequencing

Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.