Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 73.894
1.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 578-584, 2024 Jun 08.
Article Zh | MEDLINE | ID: mdl-38825903

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.


Adenocarcinoma of Lung , Anaplastic Lymphoma Kinase , ErbB Receptors , Lung Neoplasms , Mutation , Proto-Oncogene Proteins B-raf , Proto-Oncogene Proteins p21(ras) , Receptor, ErbB-2 , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Female , Retrospective Studies , Anaplastic Lymphoma Kinase/genetics , ErbB Receptors/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins c-ret/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Proto-Oncogene Proteins/genetics , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/pathology , Middle Aged
2.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 552-556, 2024 Jun 08.
Article Zh | MEDLINE | ID: mdl-38825899

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.


Adenocarcinoma , Biomarkers, Tumor , Endometrial Neoplasms , Immunohistochemistry , Sensitivity and Specificity , Uterine Cervical Neoplasms , Humans , Female , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Middle Aged , Diagnosis, Differential , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Adult , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Aged , Biomarkers, Tumor/metabolism , Antigens, Neoplasm/metabolism , Aged, 80 and over
3.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 605-609, 2024 Jun 08.
Article Zh | MEDLINE | ID: mdl-38825907

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.


Hepatoblastoma , Kidney Neoplasms , Liver Neoplasms , Neoplasms, Multiple Primary , Rhabdoid Tumor , Stomach Neoplasms , Humans , Male , Child , Female , Child, Preschool , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Infant , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Rhabdoid Tumor/genetics , Rhabdoid Tumor/pathology , Hepatoblastoma/genetics , Hepatoblastoma/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/diagnosis , Choroid Plexus Neoplasms/genetics , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/diagnosis , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/genetics , Teratoma/pathology , Teratoma/genetics , Teratoma/surgery , Brain Neoplasms/genetics , Brain Neoplasms/pathology , SMARCB1 Protein/genetics , MutL Protein Homolog 1/genetics , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/genetics , High-Throughput Nucleotide Sequencing , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology
5.
Pak J Pharm Sci ; 37(2(Special)): 443-450, 2024 Mar.
Article En | MEDLINE | ID: mdl-38822548

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.


Adenocarcinoma , Antineoplastic Agents, Phytogenic , Antioxidants , Cell Proliferation , Melissa , Phenols , Plant Extracts , Stomach Neoplasms , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Melissa/chemistry , Phenols/pharmacology , Phenols/analysis , Cell Line, Tumor , Antioxidants/pharmacology , Antioxidants/isolation & purification , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Flavonoids/pharmacology , Flavonoids/analysis , Cell Survival/drug effects
6.
S Afr J Surg ; 62(2): 33-38, 2024 May.
Article En | MEDLINE | ID: mdl-38838117

BACKGROUND: The value of the textbook outcome in pancreatic surgery (TOPS) score, a composite measure of surgical performance for quality assurance, was evaluated in a South African tertiary hospital cohort of pancreaticoduodenectomies (PD) performed for adenocarcinoma of the ampulla of Vater (AAV). METHODS: A review of all patients undergoing a PD for AAV at a single centre between January 1999 and December 2023 was performed. Demographic, operative, pathological and postoperative variables were recorded. Ten clinical and histological variables were used to construct a TOPS score. These included an R0 resection, no postoperative pancreatic fistula (POPF), no bile leak, no post-pancreatectomy haemorrhage, no delayed gastric emptying, no major postoperative complications (< Gr 3 Clavien-Dindo), no readmission to ICU, length of stay ≤ 10 days, no 30-day readmission or intervention and no 30-day mortality. A textbook outcome (TO) was defined as the fulfilment of all 10 variables. In patients in whom TO was not achieved, the reasons for failure were identified. In addition, the number of patients who had major complications and died were categorised as failure to rescue (FTR). RESULTS: A positive TOPS score was achieved in 27 of 79 (34.2%) patients undergoing a PD. Overall five-year survival after PD was 33.9%. TOPS conferred a significant 1-year survival benefit, 88.9% vs 66.7% (OR 4.12, 95% CI 1.08-15.67, p = 0.038). There was no significant difference in 5-year survival between TOPS and non-TOPS patients, 40.0% vs 32.4% (OR 1.39, 95% CI 0.48-3.99, p = 0.54). A POPF occurred in 31.6% patients, resulting in a significantly longer hospital admission, 17 vs 10 days (95% CI 2.66-11.34, p = 0.0019). Twenty-one (26.6%) patients developed a major complication, five of whom died (FTR = 6.3%). CONCLUSION: This study confirmed the value of TOPS as a useful measurement to assess hospital quality metrics and short-term survival after PD for AAV. One quarter of patients developed a major complication with a 6.3% FTR.


Adenocarcinoma , Ampulla of Vater , Common Bile Duct Neoplasms , Pancreaticoduodenectomy , Humans , Ampulla of Vater/surgery , Male , Female , Common Bile Duct Neoplasms/surgery , Common Bile Duct Neoplasms/mortality , Common Bile Duct Neoplasms/pathology , Middle Aged , Adenocarcinoma/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Retrospective Studies , Prognosis , Postoperative Complications , South Africa , Adult , Treatment Outcome
10.
BMJ ; 385: e074962, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38830686

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.


Adenocarcinoma , Esophageal Neoplasms , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Adenocarcinoma/therapy , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/pathology , Esophagoscopy/methods , Barrett Esophagus/therapy , Barrett Esophagus/diagnosis , Barrett Esophagus/pathology
11.
Langenbecks Arch Surg ; 409(1): 174, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38837064

BACKGROUND: Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4 cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. METHODS: This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. RESULTS: Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482 min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. CONCLUSIONS: Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4 cm.


Adenocarcinoma , Diaphragm , Esophageal Neoplasms , Esophagectomy , Esophagogastric Junction , Gastrectomy , Laparoscopy , Stomach Neoplasms , Humans , Esophagogastric Junction/surgery , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Female , Male , Retrospective Studies , Middle Aged , Laparoscopy/methods , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Aged , Gastrectomy/methods , Esophagectomy/methods , Diaphragm/surgery , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Plastic Surgery Procedures/methods
12.
Cancer Rep (Hoboken) ; 7(6): e2108, 2024 Jun.
Article En | MEDLINE | ID: mdl-38837874

BACKGROUND: Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. AIMS: In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. METHODS AND RESULTS: We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K-AKT-mTOR signaling pathway in PAAD. CONCLUSION: After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.


Adenocarcinoma , Biomarkers, Tumor , Cell Proliferation , Pancreatic Neoplasms , TRPM Cation Channels , Humans , TRPM Cation Channels/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/mortality , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/immunology , Cell Proliferation/genetics , Prognosis , Male , Female , Middle Aged , Gene Expression Regulation, Neoplastic , Signal Transduction , Aged , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Phosphatidylinositol 3-Kinases/metabolism , DNA Methylation
13.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824512

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.


Gastrointestinal Neoplasms , Humans , Spain/epidemiology , Middle Aged , Male , Female , Aged , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Adult , Age of Onset , Life Style , Adenocarcinoma/epidemiology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Tumor Microenvironment , Quality of Life , Incidence , Biomarkers, Tumor , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology
14.
Pan Afr Med J ; 47: 116, 2024.
Article En | MEDLINE | ID: mdl-38828424

Non-small cell lung cancer (NSCLC) is a significant global health issue with diverse molecular profiles affecting treatment responses. Yet, NSCLC's molecular epidemiology in Morocco is largely unexplored. This study focuses on NSCLC genetic mutations, specifically in adenocarcinoma, among Moroccan patients to contribute to understanding NSCLC in this population. Ninety-four patients diagnosed with lung adenocarcinoma were analyzed. Formalin-fixed paraffin-embedded tissue samples were processed, and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) was extracted using standardized protocols. Mutations were detected using the AmoyDx Pan Lung Cancer Polymerase Chain Reaction (PCR) Panel kit, and their frequencies were assessed through statistical analysis. Epidermal Growth Factor Receptor (EGFR) mutations were detected in 22.34% of patients, predominantly exon 19 deletions (66.66%) and exon 21 L858R mutations (23.80%). Anaplastic lymphoma kinase (ALK) gene fusion was observed in 3.19% of patients, and KRAS mutations in 1.06%. No mutations were found in other tested genes. A slightly higher mutation rate was noted in females (54.16%) compared to males (45.84%). The study reveals a distinct mutation profile in Moroccan NSCLC patients, with a notable prevalence of EGFR mutations, albeit lower than in some Asian populations. The significance of EGFR mutations in treatment response aligns with global findings, highlighting the importance of understanding regional molecular variations for personalized therapy. Despite limitations in sample size and clinical data, this study sheds light on the genetic landscape of NSCLC in Morocco. The observed mutation rates, particularly in EGFR, underscore the potential for targeted therapies in Moroccan NSCLC patients, emphasizing the need for further research to refine treatment strategies tailored to this population.


Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Mutation , Proto-Oncogene Proteins p21(ras) , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Morocco , Male , Female , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Middle Aged , ErbB Receptors/genetics , Aged , Adult , Proto-Oncogene Proteins p21(ras)/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Anaplastic Lymphoma Kinase/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Polymerase Chain Reaction , Aged, 80 and over , Mutation Rate , Sex Factors
15.
Saudi Med J ; 45(6): 639-642, 2024 Jun.
Article En | MEDLINE | ID: mdl-38830651

OBJECTIVES: To describe the current real-world treatment landscape, sequence of therapies, and outcomes in patients with prostate cancer (PC). METHODS: A retrospective cohort study for PC patients diagnosed at King Abdullah Medical City Cancer Center in Makkah, Saudi Arabia, between January 2011 and December 2021. Data extracted from electronic medical records. RESULTS: A total of 282 patients with PC, with a mean age of 70 years and body mass index of 27. Among them, 274 (99%) had no family history of cancer, while 164 (58%) had hypertension and 125 (44%) had diabetes mellitus. Adenocarcinoma was the most common histology, found in 275 (97%) patients, with 99 (35%) having a Gleason score of 9. Notably, 184 (65%) patients presented with metastatic disease, and 147 (52%) with bone metastasis. While 198 (70%) patients underwent surgery, 184 (65%) did not receive radiotherapy. The most common first-line metastatic therapy was abiraterone in 23 (8%) patients, followed by enzalutamide in 7 (2.5%). During the study period, 167 (59%) patients survived, with an average treatment duration of 2.5 years. CONCLUSION: This study provides insights into real-world treatment patterns and clinical outcomes in patients with PC. The findings of this study highlight the importance of adhering to treatment standards and making informed clinical decisions.


Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Saudi Arabia/epidemiology , Retrospective Studies , Aged , Middle Aged , Treatment Outcome , Phenylthiohydantoin/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Nitriles/therapeutic use , Neoplasm Grading , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Androstenes/therapeutic use , Prostatectomy , Cohort Studies , Aged, 80 and over , Benzamides
16.
Cancer Rep (Hoboken) ; 7(6): e2101, 2024 Jun.
Article En | MEDLINE | ID: mdl-38831124

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.


Adenocarcinoma , Gastrectomy , Hepatectomy , Liver Neoplasms , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Retrospective Studies , Aged , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Prognosis , Survival Rate , Aged, 80 and over , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Female
17.
Technol Cancer Res Treat ; 23: 15330338241258570, 2024.
Article En | MEDLINE | ID: mdl-38832431

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.


Adenocarcinoma , Biomarkers, Tumor , Colonic Neoplasms , Gene Expression Regulation, Neoplastic , Humans , Prognosis , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Mice , Animals , Biomarkers, Tumor/genetics , Nomograms , Computational Biology/methods , Genes, Mitochondrial , Disease Models, Animal , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Liver Neoplasms/pathology , Gene Expression Profiling , Neoplasm Staging , Male , Databases, Genetic , Mitochondria/genetics , Mitochondria/metabolism , Mitochondria/pathology , Female
18.
Cancer Immunol Immunother ; 73(8): 144, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38832979

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.


Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , B7-H1 Antigen , Biomarkers, Tumor , Esophageal Neoplasms , Esophagogastric Junction , Immune Checkpoint Inhibitors , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Female , Middle Aged , Esophagogastric Junction/pathology , Esophagogastric Junction/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Aged , Retrospective Studies , Biomarkers, Tumor/metabolism , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Aged, 80 and over , Prognosis
19.
BMC Gastroenterol ; 24(1): 156, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720257

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.


Adenocarcinoma , Carcinoma, Mucoepidermoid , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Male , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Mucoepidermoid/mortality , Carcinoma, Mucoepidermoid/surgery , Female , Middle Aged , Retrospective Studies , Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/surgery , Survival Rate , Lymphatic Metastasis/pathology , Kaplan-Meier Estimate , Prognosis , Sex Factors , Neoplasm Staging
20.
AAPS PharmSciTech ; 25(5): 104, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724836

Salinomycin (Sal) has been recently discovered as a novel chemotherapeutic agent against various cancers including prostate cancer which is one of the most commonly diagnosed cancers affecting male populations worldwide. Herein we designed salinomycin nanocarrier (Sal-NPs) to extend its systemic circulation and to increase its anticancer potential. Prepared nanoform showed high encapsulation and sustained release profile for salinomycin. The present study elucidated the cytotoxicity and mechanism of apoptotic cell death of Sal-NPs against prostate cancer both in vitro and in vivo. At all measured concentrations, Sal-NPs showed more significant cytotoxicity to DU145 and PC3 cells than Sal alone. This effect was mediated by apoptosis, as confirmed by ROS generation, loss of MMP and cell cycle arrest at the G1 phase in both cells. Sal-NPs efficiently inhibited migration of PC3 and DU145 cells via effectively downregulating the epithelial mesenchymal transition. Also, the results confirmed that Sal-NPs can effectively inhibit the induction of Prostate adenocarcinoma in male Wistar rats. Sal-NPs treatment exhibited a decrease in tumour sizes, a reduction in prostate weight, and an increase in body weight, which suggests that Sal-NPs is more effective than salinomycin alone. Our results suggest that the molecular mechanism underlying the Sal-NPs anticancer effect may lead to the development of a potential therapeutic strategy for treating prostate adenocarcinoma.


Adenocarcinoma , Antineoplastic Agents , Apoptosis , Drug Carriers , Epithelial-Mesenchymal Transition , Nanoparticles , Prostatic Neoplasms , Pyrans , Rats, Wistar , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Animals , Pyrans/pharmacology , Pyrans/administration & dosage , Apoptosis/drug effects , Humans , Rats , Cell Line, Tumor , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Drug Carriers/chemistry , Nanoparticles/chemistry , Epithelial-Mesenchymal Transition/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Cell Movement/drug effects , PC-3 Cells , Drug Delivery Systems/methods , Polyether Polyketides
...