Adenocarcinoma Patients Research Articles

292. CHEMOTHERAPY AND CHEMORADIOTHERAPY FOR ADENOCARCINOMA OF THE OESOPHAGUS AND JUNCTION WITH OLIGOMETASTASES: RESULTS OF THE TNT-OES-1 TRIAL

Abstract Background Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal and junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. Although TNT is increasingly used in rectal cancer, there are no data on combining e.g. FLOT and CROSS in esophageal cancer. This phase-II study aimed to evaluate the feasibility and safety of the TNT FLOT-CROSS combination in esophageal and junctional adenocarcinoma patients with oligometastatic disease. Methods Patients with oligometastatic (defined as a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma were treated with four biweekly cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression (RECIST v1.1) proceed to CROSS. Afterwards, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/or esophagectomy. Primary endpoint was tolerability of TNT FLOT-CROSS, defined as the proportion completing four cycles of FLOT and five cycles of chemoradiotherapy. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results Twenty patients (85% males, median age 62.5 years (interquartile range 58.3-66) were included of whom 16 (80%) had a single metastatic lesion. Eighteen patients (90%) successfully completed FLOT and fifteen (75%) completed TNT FLOT-CROSS (Figure 1). Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in twelve patients and dose-limiting of oxaliplatin in one patient. One patient had malaise grade 2. No grade 3-5 toxicities occurred during CROSS. Following TNT FLOT-CROSS, ten patients underwent four additional cycles of FLOT and toxicity resulted in treatment delay and dose reduction in seven patients and hospitalization in two patients. Six patients underwent esophagectomy of whom two underwent local treatment of metastases. The 1- and 2-year PFS was 56% and 48%. Three months after TNT FLOT-CROSS completion, DCR was 73%. Conclusion(s) This study showed that sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy. In follow-up to this study, the TNT-OES-2 study will assess the efficacy and feasibility of TNT FLOT-CROSS and TNT CROSS-FLOT in patients with resectable nodal-positive adenocarcinoma of the esophagus or esophagogastric junction.

Clinical and Genetic Characteristics of Early-Onset Lung Adenocarcinoma in a Large Chinese Cohort

BackgroundThe characteristics of early-onset lung adenocarcinoma (EOLA) have not been extensively studied. Our research aimed to comprehensively assess the clinical and genetic features of EOLA. MethodsWe conducted a retrospective analysis of surgically resected lung adenocarcinoma patients, categorizing them into the EOLA group (aged <40 years) and the late-onset lung adenocarcinoma (LOLA) group (aged >60 years). A comparative investigation of clinical, germline, and genomic features was conducted. Propensity score matching was used to balance baseline characteristics for gene mutation analysis. ResultsWe enrolled 487 EOLA and 2507 LOLA patients. EOLA patients exhibited a higher female-to-male ratio (2.55 vs 1.19) and a higher proportion of family history of lung cancer in the ground-grass opacity subgroup (12.7% vs 8.9%). The EOLA group exhibited higher rates of earlier stage in the ground-grass opacity subgroup and solid subgroup. Preinvasive adenocarcinoma was the dominant histologic subtype in the EOLA group within the ground-glass opacity subgroup (73.8% vs 25.6%). After propensity score matching, we analyzed 241 stage 0/I patients with available genetic test results. Significant disparities in gene mutation rates emerged between the EOLA and LOLA patients, including Erb-B2 receptor tyrosine kinase 2 (ERBB2; 38.0% vs 2.8%), epidermal growth factor receptor (EGFR; 36.0% vs 64.5%), MET (0.0% vs 7.1%), neurofibromin 1 (NF1; 0.0% vs. 5.7%), and anaplastic lymphoma kinase (ALK) fusion (10.0% vs 1.4%). ConclusionsEOLA patients exhibited distinct clinical and genetic characteristics compared with LOLA patients.

Laparoscopic Versus Open Pancreatoduodenectomy for Periampullary Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig.1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig.1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig.1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.

Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma

Patients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs.

5P Circulating tumor cell-derived organoids from lung adenocarcinoma patients for assessment of EGFR and KRAS mutations

5P Circulating tumor cell-derived organoids from lung adenocarcinoma patients for assessment of EGFR and KRAS mutations

1237P Association of LRRC15 protein expression with 5-year survival in lung adenocarcinoma patients

1237P Association of LRRC15 protein expression with 5-year survival in lung adenocarcinoma patients

Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy

Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). Patient and tumor characteristics were similar between LCCRT (n= 247) and SCRT (n= 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P= 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P= 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants

BackgorundPancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene. MethodsPlatinum-pretreated metastatic pancreatic cancer patients harbouring a germline variant on a DDR gene received chlorambucil at a daily oral dose of 6 mg/m2 for 42 every 56 days for the first cycle and for 14 every 28 days for the following cycles, until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival rate (PFS-6). Median progression-free survival (PFS) and overall survival (OS) were secondarily described. ResultsTwenty patients were enrolled between December 2020 and September 2022. PFS-6 was 5%, median PFS and OS were 1.6 months and 3.0 months, respectively. Grade-3 adverse events were observed in 25% of patients, while no Grade-4 toxicity was reported. ConclusionsSingle agent chlorambucil did not show sufficient signal of activity to warrant its further investigation in metastatic pancreatic cancer patients bearing a DDR-related germline alteration.

Endoscopic Resection of Stage T1 Colorectal Adenocarcinoma Followed by Surgical Intervention: a Single-center Retrospective Study

BackgroundDomestic and international guidelines recommend endoscopic resection for stage T1 colorectal adenocarcinoma with indications. However, completion surgery remains imperative for patients exhibiting high-risk factors subsequent to endoscopic procedures.ObjectiveTo investigate the evidence, pathological features, and surgical outcomes of completion surgery in patients with T1 colorectal adenocarcinoma following endoscopic resection.MethodsWe retrospectively collect data on the clinical features and treatment outcomes of patients with stage T1 colorectal adenocarcinoma who underwent endoscopic resection followed by surgical resection and those who initially completed surgical intervention at Peking University International Hospital between January 2019 and October 2022, with the aim of assessing the necessity and feasibility of surgical intervention.ResultsSeventeen patients (Group A) with high-risk factors following endoscopic procedure, especially with deep submucosal invasion and vascular or lymphatic invasion, experienced further surgical resection. The median interval between endoscopic resection and completion surgery was 23.71 days ± 15.89. Sixteen patients (Group B) underwent radical resection without any prior interventions. The surgical approach involves integration of laparoscopy and colonoscopy for precise localization and quantitative diagnosis, followed by radical surgery. The two groups demonstrated significant differences statistically with reference to tumor diameter (1.65 cm ± 0.77 vs 3.36 cm ± 1.39, P = 0.000) and the attainment of standard lymph node count (cases of detected lymph nodes larger than or equal to 12, 5 vs 12, P = 0.015). Postoperative complications and hospital stay manifested no significant disparity statistically in two groups. Patients who underwent completion surgery had no inferior outcomes compared with those who underwent direct surgery in terms of 5-year disease-free survival (Log rank test: P = 0.083, Breslow test: P = 0.089). The two groups also exhibited no significant differences statistically in the context of overall survival (Log rank test: P = 0.652, Breslow test: P = 0.758).ConclusionCompletion surgery is a safe and feasible treatment option for T1 colorectal adenocarcinoma patients with high-risk factors, particularly those with deep submucosal invasion and vascular or lymphatic invasion following endoscopic treatment. Furthermore, subsequent treatment should be chosen based on a comprehensive analysis of the patient’s history of abdominal surgery, willingness, and pathological features.

Bioinformatics analysis of BTK expression in lung adenocarcinoma: implications for immune infiltration, prognostic biomarkers, and therapeutic targeting.

In recent years, as more and more lung-cancer patients have been treated with immunotherapeutic agents, their survival has been prolonged compared to before. It is well known that BTK (Bruton's tyrosine kinase) is predominantly found in cells of the hematopoietic system. However, there is a distinct lack of literature on BTK expression in lung adenocarcinoma (LUAD) patients and its effect on the immune microenvironment. Consequently, the main goal of this investigation was to analyze how BTK expression in lung adenocarcinoma affects its progression, along with its prognostic significance, through the utilization of bioinformatics online resources and publicly available databases. Data on the sequencing results and clinical records of lung adenocarcinoma patients were gathered from The Cancer Genome Atlas (TCGA) database. Based on the expression level of BKT, TCGA categorized lung adenocarcinoma patients into BTK high-expression and low-expression groups. We investigated the effects of BKT on clinicopathologic, genomic, and immunologic characteristics of lung adenocarcinoma patients. We analyzed BTK mRNA expression in tumors and normal tissues using two key resources: Tumor Immuno Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). We analyzed the prognosis of the patients using GEPIA2 and validated the results using univariate and multivariate analyses. In addition, we assessed BTK protein expression by Human Protein Atlas (HPA). We sought to elucidate the clinical prognostic significance of BTK in The TCGA using the online tool GEPIA 2. Furthermore, to clarify the biologic roles and pathways linked to BTK, we conducted a genomic enrichment analysis of the information. To predict the proportion of various immune cell infiltrations in the immune microenvironment of lung adenocarcinoma patients diagnosed in the TCGA database, we performed an analysis using the TIMER online tool. Using TIMER and CIBERSORT, the correlation between genes co-expressed with BTK and the corresponding tumor-infiltrating immune cells was explored; finally, the relationship between BTK expression and immune infiltration and immune checkpoints in the TMB group and the high and low groups was analyzed by R language analysis using the TCGA database. The expression of BTK provides some hints about the prognosis of the patients. The high expression of BTK is involved in immune response regulation signaling pathways, leukocyte-mediated immunity, leukocyte intercellular adhesion, graft rejection, and complement. Analysis of the GEPIA 2 database showed that BTK was co-expressed with the genes FGD2, SASH3, NCKAP1L, CD53, ARHGAP30 and LPXN. Increased expression of the above-mentioned genes resulted in increased proportions of CD8 + T cells, memory CD4 + T cells, B cells, macrophages, and dendritic cells, and decreased proportions of Treg cells and TH2 cells. In addition, our study revealed a strong positive correlation between various key immune checkpoints (e.g., PDCD1, CD274, PDCD1LG2, CTLA4, HAVCR2, LAG3, TIGIT, and SIGLEC15) and BTK expression. In conclusion, increased BTK expression in lung adenocarcinoma is closely associated with prolonged survival of lung-cancer patients. Moreover, the genes classified under the BTK high-expression group exhibit significant enrichment in immune-related pathways, suggesting a potential impact on the tumor microenvironment. We investigated the potential of BTK as a tumor suppressor gene in predicting prolonged patient survival. In addition, we further investigated the possibility that BTK further affects the immunotherapeutic response of patients by influencing the microenvironment of tumor immune infiltration, but the relevant mechanisms remain to be further studied.

Value analysis of preoperative peripheral blood LMR in predicting prognosis of serous papillary ovarian adenocarcinoma

ObjectiveTo analyze the predictive effect of preoperative peripheral blood leukocyte related inflammatory indicators on the prognosis of patients with serous papillary ovarian adenocarcinoma.MethodsA retrospective analysis was conducted on the case data of 83 patients with ovarian cancer undergoing tumor cell reduction surgery admitted to our hospital from January 2017 to December 2020. Pathological findings confirmed serous papillary ovarian adenocarcinoma. Kaplan–Meier method was used to analyze the relationship between lymphocyte to monocyte ratio (LMR) and the patients survival prognosis. Analyzing factors affecting patient prognosis which using a multivariable Cox risk.ResultsThe overall survival (OS) of the patients with serous papillary ovarian adenocarcinoma in high LMR group was higher than that in the low LMR group preoperative. The disease free survival (DFS) of ovarian adenocarcinoma patients in the high LMR group was higher than that in the low LMR group preoperative. That was the low LMR indicating a poor prognosis. Single factor analysis showed that age of onset was correlated with OS and DFS, and the body mass index (BMI) was only correlated with OS. Multivariable analysis showed that the age of onset (HR = 2.571, 95% CI 1.199–5.512, P = 0.015) and BMI (HR = 0.337, 95% CI 0.158–0.718, P = 0.005) were independent risk factors for OS.ConclusionsAlthough the serous papillary ovarian adenocarcinoma patients with preoperative peripheral blood LMR reduction have poor prognosis, the correlation between LMR values and prognosis is not significant. Therefore, it is not recommended to use preoperative peripheral leukocyte related inflammatory indicators as prognostic markers for serous papillary ovarian adenocarcinoma.

Unveiling microbial dynamics in lung adenocarcinoma and adjacent nontumor tissues: insights from nicotine exposure and diverse clinical stages via nanopore sequencing technology.

Lung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer. Tumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms. the microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively. Nanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.

TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21

GC (Gastric cancer) is one of the most common malignant tumours, with over 95% of gastric cancer patients being adenocarcinoma and most gastric cancer patients having no apparent symptoms in the early stages. Finding biomarkers for early screening of gastric cancer and exploring new targets for gastric cancer treatment are urgent problems to be solved in the treatment of gastric cancer, with significant clinical outcomes for the survival rate of gastric cancer patients. The AAA+ family ATPase thyroid hormone receptor-interacting protein 13 (TRIP13) has been reported to play an essential role in developing various tumours. However, the biological function and molecular mechanism of TRIP13 in gastric cancer remain unclear. This study confirms that TRIP13 is highly expressed in gastric cancer tissue samples and that TRIP13 participates in the proliferation, migration, invasion in vitro, and tumourigenesis and metastasis in vivo of gastric cancer cells. Mechanistically, this study confirms that TRIP13 directly interacts with DDX21 and stabilises its expression by restraining its ubiquitination degradation, thereby promoting gastric cancer progression. Additionally, histone deacetylase 1 (HDAC1) is an upstream factor of TRIP13, which could target the TRIP13 promoter region to promote the proliferation, migration, and invasion of gastric cancer cells. These results indicate that TRIP13 serve is a promising biomarker for the treating of gastric cancer patients, and the HDAC1-TRIP13/DDX21 axis might provide a solid theoretical basis for clinical treatment of gastric cancer patients.

EGFR mutation based on lung laterality in adenocarcinoma type of non-small cell lung cancer

Targeted therapies have shown promise in improving survival rates for lung adenocarcinoma, a common and deadly malignancy. EGFR-targeting tyrosine kinase inhibitors (TKIs) are particularly effective among these therapies in cases with EGFR mutations. Detecting these mutations before TKI treatment is essential. Various radiological features have been linked to EGFR mutations. However, the relationship between tumor location and mutation types in Indonesian lung adenocarcinoma patients remains unexplored. This study aimed to identify the frequency of EGFR mutation in local lung adenocarcinoma cases based on the tumor location. Clinical data of lung adenocarcinoma patients (n = 272) diagnosed between 2018 and 2022 were retrospectively taken from the Department of Anatomical Pathology, Dr. Sardjito General Hospital, Yogyakarta. The qRT-PCR data of EGFR mutation status was obtained from the Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta. Descriptive analysis was performed using STATA version 14.0. EGFR mutations were found in 60.7% of patients, with 58.2% having exon 19 mutations and 21.2% exhibiting exon 21 L858R mutations. Mutation status was found to be significantly different based on the patient's gender (p = 0.022) and age (p = 0.029) but not with lung laterality (p = 0.093). The proportion of exon 19, exon 21 L858R, and uncommon mutations in the right and left lung adenocarcinoma was similar across all samples. This study found no difference between specific EGFR mutation types and tumor location in lung adenocarcinoma.

The Effect of Bilateral Orchiectomy on Total Prostate Specific Antigen (TPSA) Levels in Prostate Adenocarcinoma Patients

AbstractBackground: Hormonal therapy is one treatment option for prostate cancer. There are two main categories of hormone therapy: surgical therapy and non-surgical therapy. Orchiectomy is the surgical method of hormone therapy; medication supplementation is the non-surgical method. Many kinds of indicators are used to track the advancement of patients with prostate cancer receiving hormone therapy. tPSA levels are one of the markers that are regularly evaluated.Methods: In this retrospective study, PSA levels in patients with prostate adenocarcinoma cancer were evaluated before and after bilateral orchiectomy. Use the search terms "prostate cancer" and "orchiectomy" to find research subject data in the UGM Academic Hospital's medical records installation between 2020 and 2023. The study's findings will be shown in a graphic and statistical analysis while protecting the subjects' anonymity.Results: Most of the participants (n=18, 60.0%) have pre-orchiectomy tPSA level of more than 30 ng/mL, while only almost a quarter (n=7, 23.3%) of participants have post-orchiectomy tPSA level of more than 30 ng/mL. The two research groups (p&lt;0.0001) before and after the orchiectomy procedure, significantly differ between the two research groups based on Wilcoxon paired sample test analysis.Conclusion: TPSA levels are considerably decreased by bilateral orchiectomy.

An exploratory clinical study of β-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma.

β-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of β-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received β-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. This preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Chinese Clinical Trials Registry, identifier ChiCTR2100044088.

NLRP4 renders pancreatic cancer resistant to olaparib through promotion of the DNA damage response and ROS-induced autophagy

Olaparib has been approved as a therapeutic option for metastatic pancreatic ductal adenocarcinoma patients with BRCA1/2 mutations. However, a significant majority of pancreatic cancer patients have inherent resistance or develop tolerance to olaparib. It is crucial to comprehend the molecular mechanism underlying olaparib resistance to facilitate the development of targeted therapies for pancreatic cancer. In this study, we conducted an analysis of the DepMap database to investigate gene expression variations associated with olaparib sensitivity. Our findings revealed that NLRP4 upregulation contributes to increased resistance to olaparib in pancreatic cancer cells, both in vitro and in vivo. RNA sequencing and Co-IP MS analysis revealed that NLRP4 is involved in the DNA damage response and autophagy pathway. Our findings confirmed that NLRP4 enhances the capacity for DNA repair and induces the production of significant levels of reactive oxygen species (ROS) and autophagy in response to treatment with olaparib. Specifically, NLRP4-generated mitochondrial ROS promote autophagy in pancreatic cancer cells upon exposure to olaparib. However, NLRP4-induced ROS do not affect DNA damage. The inhibition of mitochondrial ROS using MitoQ and autophagy using chloroquine (CQ) may render cells more susceptible to the effects of olaparib. Taken together, our findings highlight the significant roles played by NLRP4 in the processes of autophagy and DNA repair when pancreatic cancer cells are treated with olaparib, thereby suggesting the potential therapeutic utility of olaparib in pancreatic cancer patients with low NLRP4 expression.

Gene mutation characteristics of clinical stage ⅠA lung adenocarcinoma and their relations with patients' long-term prognosis

Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.

The existence of heterogeneity has plunged cancer treatment into a challenging dilemma. We profiled malignant epithelial cells from 5 gastric adenocarcinoma patients through single-cell sequencing (scRNA-seq) analysis, demonstrating the heterogeneity of gastric adenocarcinoma (GA), and identified the CCKBR+ stem cell-like cancer cells associated poorly differentiated and worse prognosis. We further conducted targeted analysis using single-cell transcriptome libraries, including 40 samples, to confirm these screening results. In addition, we revealed that FOXOs are involved in the progression and development of CCKBR+ gastric adenocarcinoma. Inhibited the expression of FOXOs and disrupting cancer cell stemness reduce the CCKBR+ GA organoid formation and impede tumor progression. Mechanically, CUT&Tag sequencing and Lectin pulldown revealed that FOXOs can activate ST3GAL3/4/5 as well as ST6GALNAC6, promoting elevated sialyation levels in CCKBR+ tumor cells. This FOXO-sialyltransferase axis contributes to the maintenance of homeostasis and the growth of CCKBR+ tumor cells. This insight provides novel perspectives for developing targeted therapeutic strategies aimed at the treating CCKBR associated gastric cancer.

Assessment of baseline CCL19+ dendritic cell infiltration for predicting responses to immunotherapy in lung adenocarcinoma patients

To explore the correlation of baseline CCL19+ dendritic cell (CCL19+ DC) infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+ T cell infiltration. We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January, 2020 to December, 2023, and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+ DC and CD8+ T cell infiltration using immunofluorescence assay. We evaluated the predictive value of baseline CCL19+ DCs for patient responses to immunotherapy using receiver-operating characteristics (ROC) curves and analyzed the correlations of baseline CCL19+ DC expression with immunotherapy efficacy and CD8+ T cell and cytotoxic T lymphocyte (CTL) infiltrations. In co-culture systems of lung adenocarcinoma PC9 cells, CD8+ T cells and DCs (overexpressing CCL19 with or without anti PD-1 antibody treatment), the expressions of granzyme B, perforin, IFN-γ, and Ki-67 in T cells were analyzed using flow cytometry. The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+ DC infiltration level in lung adenocarcinoma tissues than those with poor responses. CCL19+ DC infiltration had an area under ROC curve of 0.785, a sensitivity of 75.6%, and a specificity of 62.8% for predicting immunotherapy efficacy. The expression of CD8+ T cell surface molecules Granzyme B (P<0.01), Perforin (P<0.01), IFN-γ (P<0.01) and Ki-67 (P<0.001) in patients with high expression of CCL19+ DC were higher than those in patients with low expression of CCL19+ DC. The baseline CCL19+ DC infiltration level was positively correlated with immunotherapy efficacy (P=0.003), CTL infiltration of (r=0.6657, P<0.001) and CD8+ T cell infiltration (P=0.007). In the co-cultured cells, CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+ T lymphocytes than either of the single treatments (P<0.01 or 0.001). The baseline CCL19+ DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.