Precision oncology (PO) has significantly advanced lung cancer treatment by enabling personalised therapy based on genetic mutations. However, equitable access to molecular testing and targeted therapies remains a challenge, particularly in resource-limited settings such as the Brazilian Public Health System (SUS). To identify the challenges faced by SUS in caring for patients with non-small cell lung cancer (NSCLC) in terms of access to Precision Oncology. Retrospective study with data from e-medical records of NSCLC treated between 2015-2021. 174 patients with NSCLC were included, of which 56% were females and 63% had non-squamous histology - 80% of early-stage patients and 32% of advanced-stage patients missed access to genomic testing, primarily due to short life expectancy or insufficient sample size. Only one participant underwent testing for all recommended biomarkers. Among patients with actionable mutations, 40% did not receive targeted therapy; however, regarding EGFR mutations, only 8% did not get it. Access to targeted therapy was associated with improved survival outcomes. The study highlights critical challenges and missed opportunities in the implementation of precision oncology for NSCLC management within the SUS and underscores the need for strategies to improve access to genomic testing in the public health setting.

Ampullary carcinoma (AC) is a rare disease with an abysmal prognosis and few treatment options. The molecular landscape and its therapeutic implications remain inadequately understood. This study aims to provide a clinical and genomic characterization of AC and explore opportunities for precision oncology.

We carried out a retrospective analysis of clinical and genomic features in patients with AC treated in our institution. Gene mutations were categorized into molecular pathways, and potentially targetable alterations were classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Key molecular findings were validated in an external cohort.

We included 78 patients with a median age of 66 years; 51.6% were women, and most were treated with surgery (81.2%). Histologically, they were classified as pancreaticobiliary (58.3%), intestinal (INT, 33.3%), and mixed (8.3%). The percentages of patients diagnosed at stages I, II, III, and IV disease were 18.8%, 23.4%, 32.8%, and 25.0%, respectively. Of note, the INT subtype was enriched in transforming growth factor-β pathway alterations (25.9% versus 6.1%, P = 0.03). Potentially actionable molecular alterations were found in 52% of the patients. Importantly, KRASWT tumors were enriched in potentially targetable alterations ESCAT I-IIIA both in our cohort (37.2% versus 9.4%, P = 0.006) and external validation cohort (23.0% versus 9.3%, P = 0.01), including 25.6% ERBB2 amplification/mutation, 14.0% homologous recombination deficiency status, and 7.4% microsatellite instability status. Six patients received matched targeted therapies after progression to chemotherapy, with a response rate of 50% and two patients surviving for >1 year.

AC patients are enriched in targetable alterations, especially KRASWT tumors, and could particularly benefit from precision oncology-based approaches.

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. In PDA, extracellular matrix (ECM) architectures, known as tumor-associated collagen signatures (TACSs), regulate invasion and metastatic spread in both early dissemination and late-stage disease. As such, TACS has been suggested as a biomarker to aid in pathologic assessment. However, despite its significance, approaches to quantitatively capture these ECM patterns currently require advanced optical systems with signaling processing analysis. Here, we present an expansion of polychromatic polarized microscopy (PPM) with inherent angular information coupled to machine learning and computational pixel-wise analysis of TACS. Using this platform, we are able to accurately capture TACS architectures in hematoxylin and eosin-stained histology sections directly through PPM contrast. Moreover, PPM facilitated identification of transitions to dissemination architectures (ie, transitions from sequestration through expansion to dissemination from both PanINs and throughout PDA). Last, PPM evaluation of architectures in liver metastases, the most common metastatic site for PDA, demonstrates TACS-mediated focal and local invasion as well as identification of unique patterns anchoring aligned fibers into normal-adjacent tumor, suggesting that these patterns may be precursors to metastasis expansion and local spread from micrometastatic lesions. Combined, these findings demonstrate that PPM coupled to computational platforms is a powerful tool for analyzing ECM architecture that can be used to advance cancer microenvironment studies and provide clinically relevant diagnostic information.

Aberrant iron metabolism is frequently observed in cancers, including endometrial cancer (EC). However, the role of transferrin receptor (TFRC), a key regulator of iron metabolism, remains unclear in endometrial cancer. We found transferrin receptor expression was significantly upregulated in endometrial cancer tissues compared to adjacent nontumor tissues, and high transferrin receptor levels were associated with poor prognosis. Functional studies revealed that transferrin receptor knockdown impaired endometrial cancer cell proliferation in vitro and in vivo, while transferrin receptor overexpression enhanced endometrial cancer cell proliferation. Mechanistically, transferrin receptor activated the PI3K/AKT/mTOR signaling pathway, as its knockdown suppressed the pathway, and rapamycin, an mTOR inhibitor, reversed transferrin receptor-induced pathway activation and proliferation. Modulation of the labile iron pool by ferric ammonium citrate (FAC) or deferoxamine (DFO) rescued transferrin receptor-induced biological effects. Additionally, AURKA was identified as a regulator of transferrin receptor expression. These findings demonstrate the oncogenic role of transferrin receptor in endometrial cancer and suggest that targeting iron homeostasis and the PI3K/AKT/mTOR pathway may represent potential therapeutic strategies for endometrial cancer.

Pulmonary metastasis (PM) is the most common site of distant metastasis in osteosarcoma (OS), particularly in pediatric cases, which are associated with poor prognosis. However, limited research has focused on identifying prognostic factors (PFs) for pediatric osteosarcoma with pulmonary metastasis (POPM). This study aims to identify clinical features and PFs of POPM and develop a validated nomogram to predict overall survival in POPM patients.

A retrospective analysis was conducted using OS cases from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2021). Clinical characteristics were compared between patients with and without PM. PFs were identified using Least Absolute Shrinkage and Selection Operator (LASSO) regression and evaluated through Kaplan-Meier analysis. Patients were divided into training (N = 148) and validation (N = 64) cohorts. Independent PFs were determined via Cox regression to construct a prognostic nomogram, which was assessed using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC-ROC), and calibration plots. Decision curve analysis (DCA) was used to evaluate clinical applicability.

LASSO regression identified key PFs: AJCC stage, T stage, median household income, systemic therapy, and time from diagnosis to treatment. Among these, all except T stage were validated as independent PFs via Cox regression. The nomogram demonstrated strong predictive accuracy with C-index values of 0.68 (training) and 0.71 (validation). AUC values for 1-, 3-, and 5-year survival were 0.786, 0.709, and 0.711 in the training cohort and 0.780, 0.760, and 0.776 in the validation cohort. Calibration plots showed excellent concordance between predicted and actual survival, and DCA confirmed the nomogram's clinical relevance.

AJCC stage, median household income, systemic therapy, and time from diagnosis to treatment are significant PFs for POPM survival. The validated nomogram provides a valuable tool for personalized prognostic assessment and treatment decision-making in clinical practice.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Due to the advanced stage in which HCC presents, most patients are only eligible for transarterial chemoembolization (TACE) or radioembolization (Y90). The purpose of this study is to examine the differences in survival and health-related quality of life (HRQOL) in patients diagnosed with HCC and treated with TACE or Y90.

Two hundred thirty-four patients with HCC were enrolled in studies examining HRQOL between 2003-2009. HRQOL was evaluated using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep). Between-group differences were examined using chi-square and ANOVA. Survival was assessed using Kaplan-Meier and Cox regression analyses.

Significant baseline differences between patients treated with TACE versus Y90 were found. Patients who received Y90 tended to be older (p < 0.001), female (p < 0.001), had fewer lesions (p = 0.03), had smaller tumors (p = 0.03), and were less likely to have vascular invasion (p = 0.04). After adjusting for demographic and disease-specific factors, no significant differences in HRQOL were observed at 3 months (p = 0.79) or 6 months (p = 0.75). Clinically meaningful differences were found, with the TACE group reporting greater physical, social, and emotional well-being at 3 and 6 months and greater overall HRQOL at 6 months. No significant differences in survival were found.

Treatment with TACE and Y90 was similar with regard to survival. However, TACE showed statistically and clinically meaningful benefits in physical, social/family, and emotional well-being. Further research is warranted to identify profiles of patients who may demonstrate a preferential response to either TACE or Y90.

Early diagnosis of lung cancer is crucial for improving patient outcomes. Autoantibodies against tumor-associated antigens (TAAs) found in the plasma can serve as biomarkers for lung cancer detection. Copper transporter 1 (COPT1) is abnormally expressed in several cancers including lung cancer. The purpose of this study is to explore the significance of anti-COPT1 autoantibodies in the clinical diagnosis of non-small cell lung cancer (NSCLC).

The expression level of COPT1 in NSCLC and normal tissues was analyzed based on TCGA and the Human Protein Atlas (HPA) database. Through enzyme-linked immunosorbent assay (ELISA), the expression levels of anti-COPT1 autoantibodies in plasma samples from normal controls (NC), patients with benign pulmonary nodules (BPN), and patients with NSCLC were detected in the discovery (89 NC and 89 NSCLC) and verification (321 NC, 321 BPN and 321 NSCLC) groups. The ELISA results were verified by western blotting and indirect immunofluorescence experiments.

Based on HPA and TCGA databases, the mRNA and protein levels of COPT1 were higher in NSCLC tissues than in normal tissues. The levels of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies were significantly higher in patients with NSCLC (P<0.05). Anti-COPT1-IgG and anti-COPT1-IgM could discriminate NSCLC from NC with area under the curve (AUC) values of 0.733 (95% CI: 0.694-0.771) and 0.679 (95% CI: 0.638-0.720), respectively. Additionally, the combination of anti-COPT1-IgG, anti-COPT1-IgM, and carcinoembryonic antigen (CEA) could enhance the efficacy of NSCLC diagnosis from BPN with increased AUC values.

Our study indicated the potential significance of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies as novel biomarkers for the detection of NSCLC. Furthermore, the combination of anti-COPT1-IgG and anti-COPT1-IgM improved the diagnostic value.

This study aimed to determine the role of the long noncoding RNA (lncRNA) gall bladder cancer-associated suppressor of pyruvate carboxylase (SOD2-1) in the progression of colorectal cancer (CRC). A total of 23 pairs of specimens, including CRC tissues and adjacent normal tissues, were collected, and the expression of lncRNA SOD2-1 (lnc-SOD2-1) was measured. lnc-SOD2-1 function was examined using HCT15 and HCT116 cells. A lnc-SOD2-1 overexpression vector was designed and transfected into both cell lines. MTS and colony formation assays were used to determine cell viability. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays were performed to measure apoptosis. Cell migration and invasion were evaluated using the Transwell assay. Migration and invasion markers were validated using quantitative reverse transcription-polymerase chain reaction and western blot analysis. The results indicated that the expression of lnc-SOD2-1 was downregulated in CRC tissues. lnc-SOD2-1 overexpression evidently decreased cell viability and led to the formation of fewer cell colonies. lnc-SOD2-1 overexpression induced ~ twofold higher apoptosis than the control group. lnc-SOD2-1 overexpression reduced the proportion of migratory and invasive cells to 50% and 75% of the control group, respectively. lnc-SOD2-1 overexpression significantly decreased the expression of matrix metalloproteinase-2 and -9. In conclusion, lnc-SOD2-1 may act as a tumor suppressor that inhibits the proliferation, migration, and invasion of CRC cells and induces their apoptosis.

Gender differences in medicine are playing an increasingly important role in diagnostic testing as well as therapy choices. Risk factors and mortality vary depending on gender. Diseases often manifest differently depending on gender. In diagnostic testing, gender-specific aspects need to be taken into consideration. For instance, bladder cancer diagnosis is often delayed in women compared to men as haematuria is frequently attributed to benign conditions like urinary tract infections. In therapy, decisive gender disparities should also be considered. To state an example, immune-checkpoint inhibitors have shown better response in men than in women when treating renal cell carcinoma. Furthermore, outcomes after treatment for urological tumours differ depending on gender.

Prostatic acid phosphatase (PAP) is a specific protein that is highly expressed in prostate cancer. In this study, we constructed two recombinant PAP fusion genes: PAP fused to the immunoglobulin G (IgG) Fc fragment (designated PAP-Fc) and PAP-Fc fused to the endoplasmic reticulum retention sequence KDEL (designated PAP-FcK). Transgenic Nicotiana tabacum plants expressing these recombinant macromolecular proteins (MPs) were generated using Agrobacterium-mediated transformation, and the presence of both genes was confirmed through genomic PCR. Western blot analysis validated the expression of PAP-Fc and PAP-FcK MPs, which were successfully purified via protein A affinity chromatography. Size-exclusion high-performance liquid chromatography revealed dimeric peaks for PAP-Fc (PAP-FcP) and PAP-FcK (PAP-FcKP). Bio-transmission electron microscopy demonstrated 'Y'-shaped protein particles resembling antibody structures. Moreover, PAP-FcP and PAP-FcKP exhibited a high association rate with human FcγR and FcRn. Vaccination of mice with both PAP-FcP and PAP-FcKP resulted in increased total IgG against PAP and enhanced activation of CD4+ T cells, comparable to mice immunized with PAP, which served as a positive control. These findings indicate that both plant-derived MPs can effectively induce adaptive immunity, positioning them as promising candidates for prostate cancer vaccines. Overall, plants expressing PAP-Fc and PAP-FcK represent a viable production system for antigenic macromolecule-based prostate cancer vaccines.

We compared the overall survival (OS) and cancer-specific survival (CSS) of patients who received radiotherapy and surgery, respectively, in a large population.

In this study, we counted the patients diagnosed with stage IA lung adenocarcinoma in the SEER database from 2015 to 2019. We compared the overall survival (OS) and cancer-specific survival (CSS) through Kaplan Meier analysis, balanced the differences of primary data through propensity score matching (PSM), screened independent prognostic factors through Cox regression analysis, and then compared the survival differences of different treatment methods through hierarchical analysis.

Among 11,159 patients with stage IA lung adenocarcinoma, 4254 patients chose radiotherapy alone (38.1%), and 6688 patients were finally included through the propensity score matching. The median survival time for patients with radiotherapy alone was 53 months, while the patients with surgery alone did not reach the median survival time (p < 0.001). Multivariate analysis showed that age, sex, tumor size, and household income affected the prognosis of patients. The results of the stratified analysis showed that, except in the subgroup of age ≤ 50 years, almost all subgroup analyses showed that surgical treatment achieved better results.

Radiotherapy alone can be used as an option for patients with stage IA lung adenocarcinoma who cannot tolerate surgery, but the benefit to patients is limited, and surgical treatment may still be the best choice.

Kidney and renal pelvis cancer (KCa) presents significant health challenges that require investigation. This study measured and examined trends in socioeconomic inequalities in the mortality of KCa in Canada over the period 1990-2019.

We constructed a census division level dataset pooled from the Canadian Vital Death Statistics Database (CVSD), the Canadian Census of the Population (CCP), and the National Household Survey (NHS) to measure income and education inequalities in the mortality rate of KCa in Canada over the study period. The age-standardized Concentration index (C), which measures inequality across all socioeconomic groups, was used to quantify income and education inequalities in the mortality of KCa in Canada. Trend analyses evaluated changes in these inequalities over time.

The average crude KCa mortality rates were found to be 5.97 and 3.40 per 100,000 for the male and female populations, respectively. The crude KCa mortality consistently increased over time in eastern but not western Canada. Statistically negative values of the age-standardized C index showed higher KCa mortality in the lower-income and less-educated population, particularly among females, with no changes observed over the 30-year study period.

The higher KCa mortality in socioeconomically disadvantaged groups in Canada indicates the continuing need for primary prevention through lowering smoking rates, reducing obesity, and controlling hypertension. Additionally, promoting greater use of abdominal imaging for the incidental early KCa detection can enable more effective treatment and improved survival rates, especially for females of lower socioeconomic status.

This study assessed the cost-effectiveness of nivolumab plus ipilimumab (NIVO+IPI) versus platinum-doublet chemotherapy (chemo) in untreated metastatic non-small cell lung cancer (NSCLC) using mixture-cure modelling, an approach used to analyse immuno-oncology treatments due to their underlying methods depicting delayed but durable response in some patients.

A mixture-cure economic model was developed from a US third-party payer perspective to assess the lifetime costs and benefits of NIVO+IPI versus chemo using data from Part 1 of the phase III CheckMate 227 trial with 5 years of follow-up. The model consisted of four health states: progression-free without long-term response (non-LTR), progression-free with long-term response (LTR), post-progression, and death. The primary outcomes were the incremental cost per life-year (LY) and quality-adjusted life-year (QALY) gained for NIVO+IPI versus chemo over a patient's lifetime time horizon. Model uncertainty was evaluated using one-way sensitivity analyses and probabilistic sensitivity analysis.

NIVO+IPI treatment showed a significant improvement in overall survival versus chemo; mean gain 1.69 LYs and 1.42 QALYs. The majority of the 4.04 LYs accrued by NIVO+IPI were in the LTR state (2.27 years). The incremental cost of NIVO+IPI versus chemo was US$125,321, resulting in an incremental cost/QALY gained of US$88,219.

This study suggests NIVO+IPI may be a cost-effective first-line treatment when compared with chemo in a US setting given a threshold of US$150,000 per QALY. The cost-effectiveness analysis used a mixture-cure approach, which may offer a more appropriate modelling method in immuno-oncology given LTR, by more accurately capturing the potential treatment benefit.

This study aims to investigate the effect of high-flux membrane hemodialysis on total prostate-specific antigen (tPSA) serum levels in hemodialysis patients and to evaluate the clinical significance of any observed changes.

A cross-sectional descriptive study was conducted involving 75 hemodialysis patients at An-Najah National University Hospital. tPSA and hematocrit (Hct) serum levels were measured before and after one hemodialysis session. The correlation between changes in tPSA and Hct levels was analyzed using the Statistical Package for Social Sciences (SPSS).

The mean age of the patients was 54.25 ± 15.27 years, with a mean hemodialysis duration of 40 ± 38 months. The mean tPSA levels before and after hemodialysis were 0.95 ± 0.81 ng/ml and 1.15 ± 0.96 ng/ml, respectively. Significant increases were observed in both tPSA (t = -3.264, p = 0.002) and Hct levels (t = -7.861, p < 0.001). The percentage changes in tPSA and Hct were 20% and 12%, respectively, with no significant correlation between the changes (r = 0.152, p = 0.215).

Hemodialysis significantly elevates tPSA serum levels; however, no significant correlation was found between changes in tPSA and Hct. None of the patients showed clinically significant elevations in tPSA that would necessitate prostate biopsy. Therefore, high-flux membrane hemodialysis does not appear to compromise the diagnostic value of tPSA in hemodialysis patients.

Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC.

In this multicenter international cohort study, encompassing 35 centers from 11 countries, MIPD versus OPD and subgroup analyses of LPD versus RPD were undertaken. The primary outcomes regarded the oncological resection (R1 resection rate, lymph node yield) and 5-years overall survival. Secondary outcomes were perioperative outcomes (including intra-operative variables, surgical complications and hospital stay).

In total, patients with AAC who underwent OPD (1721) or MIPD (141) were included. After propensity-score matching, 134 patients per cohort were included. The MIPD group consisted of 53 RPDs and 71 LPDs (50 per group after PSM). There was no difference in overall survival between MIPD and OPD (61.6 % vs 56.2 %, P = 0.215). In the MIPD group, operative time was longer (439 vs 360 min, P < 0.001). Between RPD and LPD, overall survival was not significantly different (75.8 % vs 47.4 %, P = 0.098) and lymph node yield was higher in RPD (21 vs 18, P = 0.014).

In conclusion, patients with AAC seem to have comparable oncological resection and perioperative outcomes from MIPD compared to the traditional OPD. Both RPD as LPD appear to be safe alternatives for patients with AAC, which warrants confirmation by future randomized studies.

Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA.

Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more), patients with hereditary syndromes and those undergoing pancreatoduodenectomy were excluded. All remaining cases as well as a subgroup of them, after propensity-score matching (nearest-neighbour-method) based on age, gender, anthropometrics, comorbidities, size and histological subtype, were analysed. The median follow-up was 21 months (IQR 10-47) after the primary intervention. Primary outcomes were rates of complete resection (R0) and complications. Groups were compared by Fisher's exact or χ2 test, Mann-Whitney-U-test and log-rank test for survival.

Of 1673 patients in the database, 1422 underwent EP and 251 TSA. Of them, 23.2% were excluded for missing or inconclusive data and 19.8% of patients for prior interventions or hereditary syndromes. Final histology showed in 24.2% of EP and 14.8% of TSA patients a histology other than adenoma or adenocarcinoma while advanced cancers were recorded in 10.9% of EP and 36.6% of TSA patients. Finally, 569 EP and 63 TSA were included in the overall analysis, with a higher rate of more advanced cases and higher R0 resection rates in the TSA groups (90.5% vs 73.1%; p<0.01), with additional ablation in the EP group in 14.4%. Severe adverse event rates were 3.2% (TSA) vs 1.9% (EP). Recurrence after histological R0 resection was 16% (EP) vs 3.2% (TSA; p=0.01), and additional therapy for R1 resection was applied in 67% of the 159 cases. Propensity-score-based matching identified 62 pairs of EP/TSA patients with comparable baseline patient and lesion characteristics. The initial R0-rate was 72.6% (EP) compared with 90.3% (TSA, p=0.02) with recurrences found in 8% (EP) vs 3.2% (TSA; p=0.07); reinterventions were more frequent in the EP group. Overall survival was comparable.

The rate of patients with poor indications due to non-neoplastic disease or advanced cancer is still high for both EP and TSA; multiple retreatments were necessary for EP. Although EP can be considered an appropriate primary therapy for certain ampullary adenomas, case selection for both therapies (especially with regard to the best step-up approach) should be studied further.

Up to 90% of cancer-related fatalities could be attributed to metastasis. Therefore, understanding the mechanisms that facilitate tumor cell metastasis is beneficial for improving patient survival and results. EMT is considered the main process involved in the invasion and spread of CRC. Essential molecular components like Wnt, TGF-β, and PI3K/Akt play a role in controlling EMT in CRC, frequently triggered by various factors such as Snail, Twist, and ZEB1. These factors affect not only the spread of CRC but also determine the reaction to chemotherapy. The influence of non-coding RNAs, especially miRNAs and lncRNAs, on the regulation of EMT is clear in CRC. Exosomes, involved in cell-to-cell communication, can affect the TME and metastasis of CRC. Pharmacological substances and nanoparticles demonstrate promise as efficient modulators of EMT in CRC. Chitosan and HA are two major carbohydrate polymers with considerable potential in inhibiting CRC. Chitosan and HA can be employed to modify nanoparticles to enhance cargo transport for reducing CRC. Additionally, chitosan and HA-modified nanocarriers, which can be utilized as potential approaches in suppressing EMT and reversing drug resistance in CRC, can inhibit EMT and chemoresistance, crucial components in tumorigenesis.

Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in PI3KCA, loss of PTEN or activation of receptor tyrosine kinases. In HPV‑negative tumors, CDKN2A (encoding p16 protein) inactivation or CCND1 (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines. Inhibitor efficacy was assessed in vitro using MTT assay and western blotting analysis. Cell cycle analysis was performed using flow cytometry and apoptosis was assessed using annexin V staining. Metabolic changes in terms of glycolysis and oxidative metabolism were measured by Seahorse XF96 extracellular Flux analysis. The results of the present study showed that both HPV‑positive and ‑negative HNSCC cell lines were sensitive to PI3Ki. In general, PI3Ki decreased PI3K/Akt/mTOR pathway activity, resulting in apoptosis, and decreased oxidative and glycolytic metabolism. The CDKi were particularly effective in blocking HPV‑negative cell line viability, showing decreased retinoblastoma expression and G1‑phase cell cycle arrest, whereas apoptosis was not induced. Thus, PI3Ki and CDKi efficiently inhibited their respective pathways and HNSCC cell viability in vitro, with the latter occurring only in HPV‑negative cell lines. Whereas PI3Ki induced apoptosis and attenuated cellular metabolism, CDKi led to cell cycle arrest. Further research should be performed to elucidate whether (a combination of) these inhibitors may be effective therapeutic agents for patients with HNSCC.

Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy. Here we performed a comprehensive proteogenomic analysis of 198 samples from Chinese AMPAC patients and duodenum patients. Genomic data illustrate that 4q loss causes fatty acid accumulation and cell proliferation. Proteomic analysis has revealed three distinct clusters (C-FAM, C-AD, C-CC), among which the most aggressive cluster, C-AD, is associated with the poorest prognosis and is characterized by focal adhesion. Immune clustering identifies three immune clusters and reveals that immune cluster M1 (macrophage infiltration cluster) and M3 (DC cell infiltration cluster), which exhibit a higher immune score compared to cluster M2 (CD4+ T-cell infiltration cluster), are associated with a poor prognosis due to the potential secretion of IL-6 by tumor cells and its consequential influence. This study provides a comprehensive proteogenomic analysis for seeking for better understanding and potential treatment of AMPAC.

Ovarian cancer (OC) represents a common neoplasm within the female reproductive tract. The prognosis for patients diagnosed at advanced stages is unfavorable, primarily attributable to the absence of reliable screening markers for early detection. An elevated neutrophil-to-lymphocyte ratio (NLR) serves as an indicator of host inflammatory response and has been linked to poorer overall survival (OS) across various cancer types; however, its examination in OC remains limited. This study seeks to identify combination diagnostic and prognostic markers for OC, aiming to improve diagnostic and prognostic efficacy, especially in the early stages.

We analyzed the targeted biomarkers in a cohort of 104 OC patients and 100 controls, which comprised 50 patients with benign ovarian tumors and 50 healthy women, using enzyme-linked immunosorbent assay (ELISA) and complete blood counting (CBC). After validating the biomarker panel, we compared the expression levels of the biomarkers in OC patients with various clinical features to assess their relevance. A biomarker panel was developed and validated with an independent cohort of 70 OC patients and 60 controls, including 30 with benign ovarian tumors and 30 healthy women. We evaluated the diagnostic accuracy using the area under the receiver-operating characteristic (ROC) curve and overall survival analysis was used for prognosis.

The results from ELISA and CBC analyses indicated that the NLR was significantly higher in patients with OC. This elevation was especially notable in those with advanced stages of the disease, lymph node metastasis, and ascites. The diagnostic performance of the NLR, when combined with CA125 and HE4, outperformed each marker used individually, especially when compared to the traditional combination of CA125 and HE4. Importantly, we observed similar results in patients with early-stage ovarian cancer and those with low levels of CA125 and HE4. In addition, these results suggest that NLR combined with CA125 and HE4 levels in OC patients have significant prognostic value.

The effective combination of serum NLR, CA125, and HE4 significantly enhances diagnostic efficiency in patients with OC. Serum NLR, CA125, and HE4 levels were identified as independent prognostic markers for OC.

Human non-small cell lung cancer (NSCLC)is a very common disease with limited treatment options. Hypoxia is a characteristic feature of solid tumors associated with the resistance of cancer cells to radiotherapy and chemotherapy. Therefore, the expression changes in cancer-resistance genes may be biomarkers of hypoxia with value in targeted therapy. The aim of the present study was to examine the effect of hypoxia on gene expression and the changes that occur in relation to drug resistance in a human NSCLC cell line (A549). A549 cells were exposed to 72-h hypoxic episodes (<1% oxygen) for a total of 10 episodes (acute). The alterations in gene expression were examined using PCR array technology after 10 episodes of acute hypoxia and compared with normoxic cells. The chemoresistance of hypoxic cells toward doxorubicin was measured using a MTT cell proliferation assay. A549 cells were affected by acute hypoxia leading to induced doxorubicin chemoresistance. Evident changes in the gene expression level were identified following episodes of acute hypoxia. The most important changes occurred in the estrogen receptor 1 (ESR1) and Finkel-Biskis-Jinkins osteosarcoma (FOS) pathways and in different nucleic transcription factors such as aryl hydrocarbon receptor and cyclin-dependent kinase inhibitor. The present study showed that exposing cells to prolonged periods of hypoxia results in different gene expression changes. There was induction of chemo-resistance due to acute hypoxia. ESR1 and c-FOS are proposed as a potential hypoxia genes in lung cancer.

Jaw osteoradionecrosis (ORN) is a major complication of head and neck cancer radiotherapy. Treatment complications account for most of the poor outcomes for head and neck cancers and the associated racial health disparities in cancer survivorship. The global incidence of jaw ORN is improving due to pre-radiotherapy patient preparations and improved head and neck cancer radiotherapy protocols. The diagnosis and management of jaw ORN are based on the patient's history and clinical presentation combined with radiological and histopathological tests. Evidence-based jaw ORN therapies focus on preventive, palliative, and surgical principles. However, new and innovative therapeutic approaches based on the cellular and molecular pathophysiological processes of jaw ORN and the jawbone's susceptibility to radiation bone damage are limited. The rationale for this narrative review is to highlight the current diagnostic approaches to jaw ORN and the pathophysiological basis for new therapeutic options for ORN.

Prior investigations have suggested a significant association between coagulation factors and ovarian cancer; however, the precise nature of the causal relationship remains elusive. Our objective is to thoroughly investigate this causal link and delineate the influence of coagulation factors on the risk of ovarian cancer through a rigorous two-sample Mendelian randomization (MR) analysis.

Genetic instrumental variables representing coagulation factors were sourced from four distinct data repositories. Summary statistics pertaining to ovarian cancer were obtained from two extensive Genome-Wide Association Studies (GWAS) for primary and replication analyses, respectively. The primary Mendelian randomization (MR) analysis utilized the inverse-variance weighted (IVW) method. To fortify the reliability of our findings, additional analyses were conducted, including the weighted-median method, MR-Egger regression, MR pleiotropy residual sum and outlier test, Cochran's Q statistic test, MR-Egger intercept analysis, and leave-one-out method, among others.

We identified four coagulation factors that were associated with the risk of ovarian cancer in the primary analysis, [odds ratio (OR): 1.365, 95% confidence interval (CI): 1.209-1.542, P <0.001 for von Willebrand factor measurement(vWF); OR: 1.060, 95% CI: 1.018-1.104, P = 0.005 for A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADATMS13); OR: 1.317, 95% CI: 1.002-1.730, P = 0.048 for activated partial thromboplastin time (aPTT); OR: 1.139, 95% CI: 1.063-1.221, P <0.001 for coagulation Factor VIII (FVIII)]. In the meta-analysis, we found that higher levels of coagulation factor VII measurement(FVII) (OR=1.0007, 95% CI: 1.0001-1.0013, P=1.0007) was associated with increased ovarian cancer risk. The results of sensitivity analyses for these coagulation factors were consistent (P<0.05).

Our systematic analyses have furnished evidence suggesting a plausible causal association between FVII and the susceptibility to ovarian cancer. Further investigations are warranted to delineate the mechanistic pathways through which coagulation factors influence the progression of ovarian cancer.

Pancreatic neoplasm, a highly aggressive and often fatal cancer, poses challenges due to late detection and nonspecific symptoms. Therefore, both early diagnosis and appropriate therapeutic approaches are necessary to augment the condition of these patients. Cancer cells undergo metabolic deregulation, which enables their proliferation, survival, and invasion. As a result, it is crucial to focus on the metabolic pathways in prevalent cancers and explore treatment strategies that target these pathways to control tumor growth effectively. This is particularly relevant in cancers like pancreatic cancer, which undergo numerous metabolic alterations. The ketogenic regimen, characterized by low carbohydrate and protein contents and high-fat sources, does not involve caloric restriction. This allows for the induction of ketogenesis and an increase in ketone bodies, while insulin and glucose levels remain low even after meals. This unique metabolic state may influence the tumor microenvironment. Given the lack of unanimous agreement on the precise role and mechanism of the ketogenic diet, this review aims to clarify the diagnostic value and accuracy of ketone bodies in various types of pancreatic tumors and explore the potential anti-cancer effects of the ketogenic diet when used alone or in conjunction with chemotherapy, also to determine the potential of the ketogenic diet to be used as adjuvant therapy. The outcomes of this study are instrumental in enhancing our understanding of the benefits and drawbacks associated with employing this diet for the management and diagnosis of pancreatic cancer.

Lynch syndrome (LS) is a hereditary autosomal dominant condition, with an increased lifetime risk of developing malignancies including colorectal cancer (CRC). Current guidelines differ in recommended colonoscopy-surveillance intervals from 1 to 2 years. Although colonoscopy is considered a safe procedure, there are risks of severe adverse events (SAEs), such as perforation and bleeding, as well as adverse events (AEs), such as abdominal discomfort and post-colonoscopy gastrointestinal infections. Colonoscopy-related bleeding and perforation rates have been reported 0.17% and 0.11%, respectively. However, there are insufficient data regarding complications of colonoscopy-surveillance for LS patients. This study aims to investigate the risk of AEs among LS patients during colonoscopy in the Stockholm region.

This retrospective cohort study includes 351 LS patients undergoing endoscopic surveillance at the Karolinska University Hospital, August 1989 - April 2021. Data from endoscopic surveillance colonoscopies were extracted from patients' medical records.

Of 1873 endoscopies in 351 LS patients, 12 complications (AEs) were documented within 30 days (0.64%) and with a total of 3 bleedings (SAEs, 0.16%). No perforations were identified.

Colonoscopy surveillance for LS patients shows a comparatively low risk of AEs per-examination. Colonoscopy complications per-patient, including both SAEs and AEs, show a significantly higher risk. Colonoscopy complications only including SAEs, show a comparatively low risk. Understanding the lifetime risk of surveillance-related colonoscopy complications is important when designing targeted surveillance programmes.

With the rapid advancement of deep learning network technology, the application of facial recognition technology in the medical field has received increasing attention.

This study aims to systematically review the literature of the past decade on facial recognition technology based on deep learning networks in the diagnosis of rare dysmorphic diseases and facial paralysis, among other conditions, to determine the effectiveness and applicability of this technology in disease identification.

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for literature search and retrieved relevant literature from multiple databases, including PubMed, on 31 December 2023. The search keywords included deep learning convolutional neural networks, facial recognition, and disease recognition. A total of 208 articles on facial recognition technology based on deep learning networks in disease diagnosis over the past 10 years were screened, and 22 articles were selected for analysis. The meta-analysis was conducted using Stata 14.0 software.

The study collected 22 articles with a total sample size of 57 539 cases, of which 43 301 were samples with various diseases. The meta-analysis results indicated that the accuracy of deep learning in facial recognition for disease diagnosis was 91.0% [95% CI (87.0%, 95.0%)].

The study results suggested that facial recognition technology based on deep learning networks has high accuracy in disease diagnosis, providing a reference for further development and application of this technology.

The cGAS-STING pathway has become a crucial role in the detection of cytosolic DNA and the initiation of immune responses. The cGAS-STING pathway not only mediates protective immune defense against various DNA-containing pathogens but also detects tumor-derived DNA to generate intrinsic anti-tumor immunity. However, abnormal activation of the cGAS-STING pathway by self-DNA can also lead to autoimmune diseases and inflammatory disorders. This article reviews the mechanisms and functions of the cGAS-STING pathway, as well as the latest research progress in female reproductive-related diseases. We focus on the regulatory mechanisms and roles of this pathway in common female reproductive disorders, discuss the clinical potential of the cGAS-STING pathway as biomarkers and therapeutic agents for female reproductive diseases, as well as the research controversies, technical issues, and biological knowledge gaps that need to be resolved. Furthermore, we provide new ideas for the treatment and prevention of these diseases.

The aim of this study was to predict gene signatures in breast cancer patients using multiple machine learning models.

In this study, we first collated and merged the datasets GSE54002 and GSE22820, obtaining a gene expression matrix comprising 16,820 genes (including 593 breast cancer (BC) samples and 26 normal control (NC) samples). Subsequently, we performed enrichment analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO).

We identified 177 differentially expressed genes (DEGs), including 40 up-regulated and 137 down-regulated genes, through differential expression analysis. The GO enrichment results indicated that these genes are primarily involved in extracellular matrix organization, positive regulation of nervous system development, collagen-containing extracellular matrix, heparin binding, glycosaminoglycan binding, and Wnt protein binding, among others. KEGG enrichment analysis revealed that the DEGs were primarily associated with pathways such as focal adhesion, the PI3K-Akt signaling pathway, and human papillomavirus infection. DO enrichment analysis showed that the DEGs play a significant role in regulating diseases such as intestinal disorders, nephritis, and dermatitis. Further, through LASSO regression analysis and SVM-RFE algorithm analysis, we identified 9 key feature DEGs (CF-DEGs): ANGPTL7, TSHZ2, SDPR, CLCA4, PAMR1, MME, CXCL2, ADAMTS5, and KIT. Additionally, ROC curve analysis demonstrated that these CF-DEGs serve as a reliable diagnostic index. Finally, using the CIBERSORT algorithm, we analyzed the infiltration of immune cells and the associations between CF-DEGs and immune cell infiltration across all samples.

Our findings provide new insights into the molecular functions and metabolic pathways involved in breast cancer, potentially aiding in the discovery of new diagnostic and immunotherapeutic biomarkers.

Ginseng polysaccharide (GPS) is an ingredient of ginseng with documented anti-tumor properties. However, its effect on colon cancer and the underlying molecular mechanisms have not been investigated clearly.

Cell viability of HT29 and CT26 cells treated with different concentrations of GPS was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot assay was used to detect the expression of apoptotic proteins, while the mRNA levels were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell migration assays were used to examine the migration and invasion of cells.

The results revealed that GPS effectively suppressed the proliferation of HT29 and CT26 cells. We demonstrated an upregulation of apoptotic proteins in GPS-treated cells, including Bax, cleaved Caspase-3, and p-p53. GPS treatment also increased the mRNA levels of cytochrome C and Bax. Furthermore, the results showed that GPS treatment concurrently promoted the activation of nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) inflammasome. Transwell migration assays showed that GPS inhibited the migratory and invasive abilities of colon cancer cells. As expected, inhibition of NLRP3 expression using INF39 attenuated the inhibitory effect of GPS on migration and invasion. Upon NLRP3 inhibition, GPS-induced apoptosis was dramatically alleviated, accompanied by a reduction in the expression of apoptotic proteins.

In conclusion, this research provides compelling evidence that the GPS-induced NLRP3 signaling pathway plays a pivotal role in apoptosis of colon cells, suggesting potential clinical implications for the therapeutic intervention of colon cancer. Thus, GPS might be a promising anti-tumor drug for the treatment of colorectal cancer.

Anal canal squamous cell carcinoma (SCC) is a relatively uncommon neoplasia, and it is mostly a local-regional cancer, of low metastatic potential (only 15%), resulting in cure in most cases treated with definitive chemoradiation. On the other hand, its incidence has been steadily increasing over the last decades, which makes it an important public health problem. In an effort to provide surgeons and oncologists who treat patients with anal cancer with the most updated information based on the best scientific evidence, the Brazilian Society of Surgical Oncology (SBCO) has produced the present guideline for the management of anal canal SCC, focused on the main topics related to daily clinical practice.

The SBCO developed the present guidelines to provide recommendations on the main topics related to the management of anal canal squamous cell carcinoma (SCC) based on current scientific evidence.

Between October 2022 and January 2023, 14 experts met to develop the guidelines for the management of anal canal cancer. A total of 30 relevant topics were distributed among the participants. The methodological quality of a final list with 121 sources was evaluated, all the evidence was examined and revised, and the management guidelines were formulated by the 14-expert committee. To reach a final consensus, all the topics were reviewed in a meeting that was attended by all the experts.

The proposed guidelines contained 30 topics considered to be highly relevant in the management of anal canal cancer, covering subjects related to screening recommendations, preventive measures, tests required for diagnosing and staging, treatment strategies, response assessment after chemoradiotherapy, surgical technique-related aspects, and follow-up recommendations. In addition, screening and response assessment algorithms, and a checklist were proposed to summarize the important information and offer an updated tool to assist surgeons and oncologists who treat anal canal cancer and in providing the best care to their patients.

These guidelines summarize recommendations based on the most current scientific evidence on relevant aspects of anal canal cancer management and are a practical guide to help surgeons and oncologists who treat anal canal cancer make the best therapeutic decisions.

Glioblastoma patients may develop functional deficits post-operatively that affect activities of daily living and result in worse outcomes. The Activity Measure for Post-Acute Care (AM-PAC) instrument assigns patients basic mobility and daily activity scores, but it is unknown if these scores correlate with post-operative outcomes in glioblastoma patients.

Adult (≥18 years) glioblastoma patients evaluated by physical/occupational therapy after resection at a single instution (June 2008-December 2020) were identified. Patient demographics, post-operative AM-PAC scores, and clinical outcomes were collected. Multivariate regression identified associations between AM-PAC scores and post-operative outcomes.

600 patients were included (mean age 59.3 years, 59.2 % male); 151 (25.3 %) and 246 (43.8 %) patients had low mobility (<42.9) and activity (<39.4) scores, respectively. 103 (17.2 %) and 177 (29.5 %) patients experienced extended lengths of stay (LOS) in the ICU (≥2 days) and overall (≥7 days), respectively. 154 (25.7 %) patients had non-home discharges. The 30-day readmission rate was 13.7 %. In multivariate analysis, low mobility scores correlated with increased odds of extended overall (p < 0.0001) and ICU (p = 0.0004) LOS, non-home discharge (p < 0.0001), and 30-day readmission (p = 0.0405). Low activity scores correlated with extended overall LOS (<0.0001) and non-home discharge (p < 0.0001). In log-rank analysis, median survival time was shorter for patients with low mobility (9.5 vs. 14.7 months, p < 0.0001) and activity (10.6 vs. 16.3 months, p < 0.0001) scores than for high-scoring patients.

AM-PAC basic mobility and daily activity scores are associated with outcomes after glioblastoma resection. These easily obtainable scores may be useful for prognosticating and guiding decision making in post-operative glioblastoma patients.

Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our goal was to analyse temporal improvements and provide contemporary population-based benchmarks for outcomes following pancreatoduodenectomy.

We empanelled a cohort comprising all patients in Sweden with pancreatic or periampullary cancer treated with pancreatoduodenectomy from 1964 to 2016 and achieved complete follow-up through 2016. We analysed postoperative deaths and disease-specific net survival.

We analysed 5923 patients with cancer of the pancreas (3876), duodenum (444), bile duct (504), or duodenal papilla (963) who underwent classic (3332) or modified (1652) Whipple's procedure or total pancreatectomy (803). Postoperative deaths declined from 17.2% in the 1960s to 1.6% in the contemporary time period (2010-2016). For all four cancer types, median, 1-year and 5-year survival improved substantially over time. Among patients operated between 2010 and 2016, 5-year survival was 29.0% (95% confidence interval (CI): 25.5, 33.0) for pancreatic cancer, 71.2% (95% CI: 62.9, 80.5) for duodenal cancer, 30.8% (95% CI: 23.0, 41.3) for bile duct cancer, and 62.7% (95% CI: 55.5, 70.8) for duodenal papilla cancer.

There is a continuous and substantial improvement in the benefit-harm ratio after pancreatoduodenectomy for cancer.

The incidence of brain tumors has increased in elderly population overtime. Their eligibility to a major surgery remains a questionable subject. This study evaluated prognostic factors and 30-days morbidity and mortality in octogenarian population who underwent craniotomy for resection of brain tumor.

A total of 154 patients were divided into two different groups: patients above 80 years old and patients below 65 years old. In both groups, patients were stratified based on diagnosis with benign tumors [meningioma] and malignant tumors [high-grade gliomas and metastases]. Multivariable logistic regression model with backward elimination method was utilized to identify the independent risk factors for 30-days readmission and post-operative complications.

The analysis revealed no significant difference in 30-day readmission (p = 0.7329), 30-day mortality (0.6854) or in post-operative complication (p = 0.3291) between age ≥ 80 and age ≤ 65 groups. A longer length of stay (LOS) was observed in the older patients (p = 0.0479). There was a significant difference in the pre-post KPS between the two groups (p < 0.0001). ASA (p = 0.0315) and KPS (p = 0.071) were found as important prognostic factors associated with post-operative mortality in both groups.

Octogenarians can withstand craniotomy without any significant increase in 30-day readmission, 30-day mortality and post-operative complications as compared to patients younger than age 65. The ASA score (>3) and/or KPS (<70) were the most important prognostic factors for 30-days readmission and mortality.

This study aimed to evaluate the effects of microRNA-650 (miR-650) on melanoma metastasis and reveal the regulatory relationship between miR-650 and the inhibitor of growth family member 4 (ING4).

miR-650 expression was determined in human melanoma WM115 and A-375 cells. WM115 cells were transfected with miR-650 mimic or mimic control. The invasion and migration abilities of transfected WM115 cells were analyzed using Transwell and wound healing assays, respectively. Then, miR-650-overexpression lentivirus vector was constructed and transfected into WM115 cells. After injection into the mice, the number of micro-metastatic foci in the lung tissues was counted. A regulatory relationship between miR-650 and ING4 was identified in WM115 and A-375 cells.

The miR-650 expression was upregulated in WM115 and A-375 cells. WM115 cells transfected with the miR-650 mimic exhibited higher invasive and migratory abilities than mock cells or cells transfected with negative control (NC). The number of micro-metastatic foci was significantly higher in mice injected with Lenti-miR-650 than that in those injected with mock or NC controls. Transfection with miR-650 mimic observably inhibited the expression of ING4 in WM115 and A-375 cells, whereas transfection with miR-650 inhibitor had the opposite effect. Dual-luciferase reporter gene assay showed that the miR-650 mimic inhibited the luciferase activity of ING4.

miR-650 promotes melanoma metastasis by downregulating ING4 expression.