Small Cell Lung Carcinoma Research Articles

Correlation between p53 immunoexpression and TP53 mutation status in extrapulmonary small cell neuroendocrine carcinomas and its association with patient survival.

Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Despite its morphological similarity to lung small cell carcinomas, its oncogenesis remains uncertain. One hundred and seventy-one EP-SCNC were enrolled in a multicenter study, and all tissue samples underwent an immunohistochemical p53 analysis. One hundred twenty-five samples were molecularly analyzed using next-generation sequencing (NGS), comprising DNA and RNA analysis. p53 normal/wild type expression was detected in 68 cases (39.8%), whereas aberrant expression was detected in 103 cases (60.2%). Molecular TP53 alteration was detected in 92 out of 125 tumors (73.6%). The TP53 mutation was shown to be prognostic andassociated with shorter overall survival (p = 0.041). The multivariate analysis of p53 and TP53 mutational status found that it impacted overall survival relative to distinct sites of tumor locations (p = 0.004 and p = 0.001, respectively). Age did not influenced survival in the multivariate analysis of p53 and TP53 (p = 0.002; p < 0.001resp.). Among tumors with paired immunohistochemical and molecular results, 108 exhibited concordance between the immunohistochemical and molecular analysis, whereas 17 were discordant. Accordingly, p53 aberrant expression was tightly associated with a TP53 mutation (p < 0.001). In discordant cases, molecular analysis revealed no alteration in three tumors with p53 overexpression. In contrast, in 14 tumors with wild-type p53 expression, TP53 genetic alteration was detected. Possible causes of discordance are discussed in this manuscript. Furthermore, the incidence of aberrant p53 expression / TP53 molecular alteration was noticeably lower in EP-SCNC than in small-cell lung carcinomas. Therefore, in EP-SCNC, other driver mutations should be sought since personalized therapy can improve patient prognosis.

The Pancreatic Hypermetabolic Lesions of Lung Carcinoma Patients in F-18-Fluorodeoxyglucose PET-CT: Correlation with Pathology

Aim: The ratio and results of the hypermetabolic lesions of the pancreas in lung carcinoma patients in FDG PET-CT which is rare, wasn’t sufficiently evaluated previously in the literature. The aim of this study was to determine these lesions’ pathologic correlations. Materials and Methods: The F-18 FDG PET/CT images of the 516 patients with Lung Carcinoma was evaluated retrospectively by an Experienced Nuclear Medicine Physician and correlation of Pathology results were analyzed. Results: The ratio of the pancreatic hypermetabolic lesions were 7% (36 patients). Pathology results revealed small cell lung carcinoma metastasis in 23, adenocarcinoma in 8, squamous cell carcinoma in 1 and atypical carcinoid tumor in 1 and other pathology types in rest of the patients in primary Lung Carcinoma. Five of the pancreatic lesions pathology results could be obtained and three were small cell lung carcinoma, one of them was adenocarcinoma and the squamous cell carcinoma in other one. Conclusion: The hypermetabolic pancreatic lesions in Lung Carcinoma patients in F-18 FDG PET/CT should be evaluated and considered carefully. Since unexpected pathology results could be achieved.

Paraneoplastic syndrome with intestinal pseudo-obstruction in a patient with small cell lung carcinoma: a case report and literature review.

Paraneoplastic chronic intestinal pseudo-obstruction (CIPO) is a rare manifestation associated with small cell lung carcinoma and other malignancies. In this report, we present a challenging case involving a 60-year-old man with small cell lung carcinoma who developed symptoms of intestinal pseudo-obstruction, including abdominal distention, pain, and obstipation. Despite receiving extensive treatment with intravenous gamma globulin and glucocorticoids, the patient's symptoms did not improve, ultimately resulting in irreversible nervous system damage. Through a comprehensive literature review, we explore the underlying mechanisms of paraneoplastic CIPO and discuss its diagnostic and therapeutic approaches. We emphasize the significance of timely detection of related antibodies for early diagnosis and treatment of CIPO to improve patient outcomes.

Small cell lung carcinoma with YAP1 expression and SMARCA4-deficient undifferentiated tumors

Small cell lung carcinoma with YAP1 expression and SMARCA4-deficient undifferentiated tumors

Small cell lung carcinoma metastatic to the stomach: Commonly overlooked, limited treatment options.

Small cell lung carcinoma metastatic to the stomach, whether synchronous or metachronous, is a rare phenomenon accounting for < 0.5% of lung cancers. Hence it can be overlooked by clinicians resulting in delayed diagnosis. This manuscript comments on Yang et al's article which reported 3 such cases. The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei, scant cytoplasm, brisk mitoses and necrosis. This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin, thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index. Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma. The predominant mechanism of spread is most likely hematogeneous. Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/radiotherapy and palliative surgery in select cases. Though outcomes have not changed much in the last several decades, the recent Food and Drug Administration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes. Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis.

Comparison of molecular subtype composition between independent sets of primary and brain metastatic small cell lung carcinoma and matched samples.

Recent advances in the subclassification of small cell lung carcinomas (SCLCs) may help to overcome the unmet need for targeted therapies and improve survival. However, limited information is available on how the expression of the subtype markers changes during tumour progression. Our study aimed to compare the expression of these markers in primary and brain metastatic SCLCs. Immunohistochemical analysis of the subtype markers was performed on 120 SCLCs (including 10 matched samples) and SCLC xenografts. Compared to primary SCLCs, there was a significant increase in the proportion of mixed subtypes in brain metastases, with a rate of ASCL1high/NeuroD1high and ASCL1high/NeuroD1high/YAP1high subtypes increasing to 48% and 18%, respectively. The subtype of the paired samples matched in only one-third of the cases. Although we did not observe a significant change after chemotherapy, a continuous decrease in ASCL1 expression coupled with an increase in the NeuroD1 expression was detected in the xenografts in a long-term experiment. Our results indicate that the expression of subtype markers frequently changes during disease progression, and subtype analysis of the primary SCLC may not provide accurate information about the characteristics of the recurrent or metastatic tumour. Therefore, repeated sampling and subtyping may be necessary for subtype-specific targeted therapy.

Radiomic signatures of brain metastases on MRI: utility in predicting pathological subtypes of lung cancer.

The pathological sub-classification of lung cancer is crucial in diagnosis, treatment and prognosis for patients. Quick and timely identification of pathological subtypes from imaging examinations rather than histological tests could help guiding therapeutic strategies. The aim of the study is to construct a non-invasive radiomics-based model for predicting the subtypes of lung cancer on brain metastases (BMs) from multiple magnetic resonance imaging (MRI) sequences. One hundred and sixty-one patients of primary lung cancer with synchronous BMs [121 with adenocarcinoma (AD); 40 with small cell lung carcinoma (SCLC)] were enrolled in the study (129 and 32 in the training set and validation set). A total of 960 radiomics features were extracted from multiple MRI sequences [fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), contrast-enhanced T1 weighted imaging (CE-T1WI) and contrast-enhanced susceptibility weighted imaging (CE-SWI)] and four clinical features were recorded. Forty-one key features were selected by the least absolute shrinkage selection operator (LASSO). The machine learning (ML) models for predicting AD and SCLC with radiomics features alone and with radiomics features plus clinical features were constructed using classifiers of logistic regression (LR), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGBoost). The prediction performance of models was evaluated by accuracy (ACC), sensitivity (SEN), specificity (SPE), F1 score and area under the curves (AUC). The AUCs of LR, RF, SVM and XGBoost models were 0.8177 vs. 0.7604, 0.8177 vs. 0.7839, 0.4792 vs. 0.8594 and 0.9062 vs. 0.8750, respectively, when using radiomics features alone and radiomics features plus clinical features. In the best-performing model using XGBoost, combination of conventional MRI sequences and CE-SWI had better sub-classification performance than conventional MRI sequences. Radiomics of BMs from multiple MRI sequences provides high discriminatory performance in predicting AD and SCLC using classifiers of LR, RF and XGBoost, and can serve as a potential useful tool to non-invasively distinguish pathological subtypes of lung cancer.

Central sleep apnea as an initial presentation of small cell lung carcinoma with anti-Hu antibody-related paraneoplastic neurologic syndrome.

Anti-Hu antibody-related paraneoplastic neurologic syndrome (PNS), a rare disease primarily associated with small cell lung carcinoma, is characterized by diverse neurologic manifestations. Central sleep apnea, although rare, is specific to anti-Hu antibody-related PNS. Herein, we present a case of out-of-hospital cardiac arrest attributed to hypercapnic central sleep apnea and detail the subsequent workup that revealed anti-Hu brainstem encephalitis. A malignancy survey revealed mediastinal small cell carcinoma. The patient was treated by tumour excision, chemotherapy, plasma exchange, and high-dose glucocorticoids. Though the neurologic damage caused by anti-Hu antibody was documented to be relatively irreversible in literatures, such hypercapnic central sleep apnea resolved in our case about 1 month later.

Methylation status of selected genes in non-small cell lung carcinoma - current knowledge and future perspectives.

DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC. Seventy-five studies were reviewed, focusing on the promoter methylation of key genes, such as APC, BRCA1, CDH1, CDH13, DAPK1, DLEC1, FHIT, GSTP1, hMLH1, MGMT, CDKN2A, RARβ, RASSF1, RUNX3, and TIMP3. These studies explored diagnostic, prognostic, epidemiological, and therapeutic aspects across NSCLC subtypes. Additionally, mutational profiles of TP53, RB1, KEAP1, and STK11 and expression patterns of ASCL1, DLL3, and NOTCH were analyzed. The findings suggest that LCNEC may serve as a biological bridge between non-small cell and small-cell lung carcinoma. Our analysis highlights that the methylation status of selected genes could enhance diagnosis, prognosis, and personalized treatment strategies in patients with NSCLC, particularly those with LCNEC.

Primary pleural small-cell carcinoma with paraneoplastic syndrome: a case series

Small-cell lung carcinoma (SCLC) is a highly aggressive neuroendocrine tumour that usually presents as a centrally located mass or mediastinal lesion. It clinically manifests as a feature of airway obstruction or haemoptysis with paraneoplastic syndrome being common entity. Extrapulmonary origin and metastatic pleural involvement are rare. Primary pleural involvement without lung lesion is extremely rare in small-cell cancer. In this case series, we are describing clinical features with radiological findings and thoracoscopic appearance and histopathology of three cases diagnosed as small-cell lung cancer with primary pleural involvement and different paraneoplastic syndrome with their response to chemotherapy.

Association between the dietary inflammatory index and risk of lung cancer: a multi-centered case-control study.

Dietary factors might contribute to the risk of lung cancer by increasing the concentration of inflammatory markers. The literature-derived Dietary Inflammatory Index (DII) has been established to evaluate the inflammatory potential of diet correlated with inflammatory markers. The association between DII scores and the risk of lung cancer has been conflicting. So, in the current study, we aimed to assess the effect of pro-inflammatory dietary patterns measured with DII and the risk of lung cancer. A multi-center case-control study was carried out on 616 patients with lung cancer and 3412 healthy controls. Dietary intakes were collected using a 131-item food frequency questionnaire during a face-to-face interview. The DII scores including thirty-six nutrients were calculated after energy adjustments. Finally, the association between DII level and the risk of lung cancer was evaluated by performing a multi-variable regression method after adjusting for potential confounders. The risk of overall lung cancer, small cell, and squamous cell carcinoma was elevated in the third tertile compared to the first tertile of the DII score, (odds ratio [OR] T3 vs. T1 of overall lung cancer = 1.38 (95% confidence interval [CI] 1.08-1.77), P trend = 0.01, OR T3 vs. T1 of squamous cell lung cancer = 1.82 (95% CI 1.02-3.24), P trend = 0.04, OR T3 vs. T1 of small cell lung cancer = 1.66 (95% CI 1.08-2.54), P trend = 0.019). However, no increase was observed in the risk of adenocarcinoma by adherence to a pro-inflammatory dietary pattern. A positive link was found between DII and the risk of overall lung cancer, small-cell, and squamous-cell lung cancer. However, there was no association between DII and the risk of lung adenocarcinoma.

Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression

Small cell lung carcinoma (SCLC) is a highly malignant cancer with early metastatic dissemination and poor clinical outcomes. Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, including the frequently occurring rapamycin-insensitive protein (RICTOR) amplification, have been described in these tumours. Moreover, the associated mTOR hyperactivity could be exploited for personalised treatment. Our aim was to study mTOR activity, RICTOR amplification, and their role during SCLC progression. In situ mTOR activity and Rictor expression were characterised by immunohistochemistry in 50 primary and 50 brain metastatic tumours, and 14 paired SCLC patient samples. RICTOR copy number changes were analysed by fluorescence in situ hybridisation of the paired SCLC patient samples and in vivo experiments. Additionally, in vitro sensitivity to cisplatin and mTOR inhibitors was evaluated in SCLC cell lines harbouring RICTOR amplification and other mTOR pathway mutations. High Rictor expression and mTOR complex 2 (mTORC2) hyperactivity were significantly associated with brain metastases and worse overall survival. An increase in RICTOR copy number was observed in paired samples during progression. The importance of these alterations was confirmed both by the sensitising effect of vistusertib in vitro and the RICTOR copy number/expression changes in xenografts. Our study highlights the role of mTORC2 in SCLC progression. Early detection of RICTOR amplification in primary tumours and targeting mTORC2 in these cases may represent a promising novel strategy to develop personalised therapy for metastasis prevention.

Chromothripsis-Mediated Small Cell Lung Carcinoma.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis-massive, localized chromosome shattering-recurrently involving chromosome 11 or 12 and resulting in extrachromosomal amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers. Significance: Here, we provide the first detailed description of a unique SCLC subset lacking RB1/TP53 alterations and identify extensive chromothripsis and pathogenetic links to pulmonary carcinoids as its hallmark features. This work defines atypical SCLC as a novel entity among lung cancers, highlighting its exceptional histogenesis, clinicopathologic characteristics, and therapeutic vulnerabilities. See related commentary by Nadeem and Drapkin, p. 8.

Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells.

Background: Small-cell lung cancer (SCLC) has a poor prognosis because it is often diagnosed after it has spread and develops multi-drug resistance. Epibrassinolide (EB) is a plant steroid hormone with widespread distribution and physiological effects. In plants, EB-activated gene expression occurs via a GSK-mediated signaling pathway, similar to Wnt-β-catenin signaling in animal cells that is elevated in cancer cells. Methods: This mechanistic parallel prompted investigations of the molecular interactions of EB on drug-sensitive (H69) and multi-drug-resistant (VPA) SCLC cells. Cellular and molecular investigations were performed. Results: Pharmacologic interactions between EB and the Wnt signaling inhibitors IGC-011 and PRI-724 were determined by the combination index method and showed antagonism, indicating that EB acts on the same pathway as these inhibitors. Following incubation of drug-sensitive and drug-resistant SCLC cells with EB, there was a reduction in β-catenin (e.g., 3.8 to 0.7 pg/µg protein), accompanied by a reduction in β-catenin promoter activity, measured by firefly luciferase-coupled promoter element transfection. Cellular β-catenin concentration is regulated by the active form of GSK3β. In Wnt signaling, active GSK3β is converted to inactive pGSK3β, thereby increasing the concentration of β-catenin. After incubation of SCLC cells with EB, there was a reduction in the inactive form (pGSK3β) and a relative increase in the active form (GSK3β). In vitro enzyme assays showed that EB did not inhibit purified GSK3β, but there was non-competitive inhibition when SCLC cell extracts were used as the source of enzyme. This indirect inhibition by EB indicates that it may act on the Wnt pathway by blocking the phosphorylation of GSK3β. The protein levels of three SCLC tumor markers, namely, NSE, CAV1, and MYCL1, were elevated in drug-resistant SCLC cells. EB incubation led to a significant reduction in the levels of the three markers. Two major effects of EB on SCLC cells are the promotion of apoptosis and the reversal of drug resistance. Transcriptional analyses showed that after exposure of SCLC cells to EB, there were increases in the expression of genes encoding apoptotic inducers (e.g., BAX and FAS) and effectors (e.g., CASP3) and reductions in the expression of genes encoding apoptosis inhibitors (e.g., survivin). PGP1 and MRP1, two membrane efflux pumps expressed in SCLC cells, were elevated in drug-resistant cells, but EB incubation did not affect these protein levels. Cellular assays of drug efflux by PGP1 showed an increase in drug-resistant cells, but EB did not alter efflux activity. Following exposure to human liver microsomes, EB was metabolized by NADPH-dependent oxidation and UDPG-dependent glucuronidation, as evidenced by the elimination of EB cytotoxicity against SCLC cells. Conclusions: Taken together, these data indicate that EB, a steroid hormone in plants consumed in the human diet, is pharmacologically active in drug-sensitive and drug-resistant SCLC cells in the Wnt signaling pathway, alters apoptotic gene expression, and is a substrate for microsomal modifications.

Clinical features and prognostic factors of IV combined small cell lung cancer: A propensity score matching analysis.

Nowadays, the characteristics and treatment of combined small-cell lung carcinoma (CSCLC) remain controversial. This study aimed to analyze the features of clinical demographics, survival outcomes and treatment modalities among IV CSCLC, IV SCLC and IV NSCLC, to provide more evidence for the study of IV CSCLC. All CSCLC, SCLC and NSCLC patient data were obtained from the SEER database (2010-2020). Pearson's χ2 test was used to compare the differences in clinical characteristics. Propensity score matching (PSM) was utilized to balance the bias of the variables between patients. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. KM analysis was used to calculate survival. Adjusted analyses for the primary outcome of different treatment modalities of IV CSCLC, IV SCLC and IV NSCLC were performed using Cox regression models. A total of 493 patients with IV CSCLC, 35503 patients with SCLC, 122807 patients with IV NSCLC were included in this study. The demographic characteristics and tumor characteristics of the three groups were different. Before PSM, there were significant differences in OS and CSS among IV CSCLC, IV SCLC and IV NSCLC, After PSM, there was a significant difference in OS and CSS between the IV CSCLC and IV NSCLC. Risk/protective factors for OS and CSS were different in three groups. Chemotherapy, radiotherapy, and surgery can improve IV CSCLC's survival time. The combination of surgery and chemoradiotherapy treatment group for patients with IV CSCLC demonstrated best OS compared to control treatment groups, and the surgery combined chemotherapy treatment group exhibited the best CSS. Additionally, for select patients with stage IV CSCLC who have missed the window for surgical intervention at the time of initial diagnosis, chemoradiotherapy presents a viable and effective treatment option. The clinical characteristics IV CSCLC, IV SCLC and IV NSCLC were significantly different. The prognosis for IV CSCLC is notably poorer than IV NSCLC, similar to IV SCLC. Surgery combined therapy emerged as the preferred treatment modalities and chemoradiotherapy was a good choice for patients who have lost the indication of surgery for patients diagnosed with IV CSCLC.

Histological transformation in lung adenocarcinoma: Insights of mechanisms and therapeutic windows.

Histological transformation from lung adenocarcinoma (ADC) to small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC), squamous cell carcinoma (SCC), and sarcomatoid carcinoma (PSC) after targeted therapies is recognized as a mechanism of resistance in ADC treatments. Patients with transformed lung cancer typically experience a poor prognosis and short survival time. However, effective treatment options for these patients are currently lacking. Therefore, understanding the mechanisms underlying histological transformation is crucial for the development of effective therapies. Hypotheses including intratumoral heterogeneity, cancer stem cells, and alteration of suppressor genes have been proposed to explain the mechanism of histological transformation. In this review, we provide a comprehensive overview of the known molecular features and signaling pathways of transformed tumors, and summarized potential therapies based on previous findings.

Comprehensive assessment of schiff base derived from 4-Chloroaniline and 2-Formylphenol: Molecular architecture, experimental with computational bioactivity profiling, emphasizing anticancer efficacy against pulmonary and mammary carcinoma cell models

This study thoroughly analyses the structural and biological properties of a Schiff base compound synthesized from the condensation of 2-formyl phenol and 4-chloroaniline. Single crystal X-ray diffraction examination indicated that the compound crystallizes in the monoclinic space group P21/c, with unit cell parameters a = 13.4232(15) Å, b = 5.7860(6) Å, c = 14.699(2) Å, β = 106.048(6) °, and Z = 4. The molecular structure has an E configuration around the C = N double bond, with a bond length of 1.266(2) Å, and includes an intramolecular O—H⋯N hydrogen bond. Hirshfeld surface analysis elucidated intermolecular interactions inside the crystal lattice, emphasizing dominant hydrogen-hydrogen, hydrogen-chlorine, and carbon-hydrogen contacts. The chemical exhibited concentration-dependent antioxidant and anti-inflammatory effects. Studies on DNA interactions indicate van der Waals forces between the ligand and nucleic acid, whereas it demonstrated considerable binding affinity for BSA with a ΔG value of -6.9 kcal/mol. ADME study revealed values within the recommended range, indicating advantageous pharmacokinetic characteristics. PASS filter-based cytotoxicity predictions indicated significant anti-cancer efficacy against breast adenocarcinoma, small cell lung carcinoma, and lung cancer. Toxicological assessments in diverse models indicated no possible irritation to skin and ocular tissues, highlighting its safety profile for therapeutic use. This research advances our comprehension of Schiff bases with halogen substituents and their prospective uses in chemistry and biology.

Gastric metastasis of small cell lung carcinoma: A rare but noteworthy entity to consider.

Small cell lung carcinoma (SCLC) is an aggressive malignancy known for its propensity for early and extensive metastatic spread. Gastric metastasis, where cancer cells disseminate from the lung to the stomach, is a rare but increasingly recognized complication of SCLC. This review provides a comprehensive overview of gastric metastasis in SCLC, addressing its clinical significance, diagnostic challenges, management strategies, and prognosis. Additionally, it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis. Gastric metastasis in SCLC, though infrequent, is clinically significant and often indicates advanced disease with a poor prognosis. SCLC typically metastasizes to the liver, brain, bones, and adrenal glands, with the stomach being an unusual site. The incidence of gastric metastasis ranges from 1% to 5% in autopsy studies, although this may be underestimated due to diagnostic difficulties and asymptomatic early lesions. Diagnosing gastric metastasis presents several challenges, including the asymptomatic nature of many cases, limitations of conventional imaging techniques, and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy. Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers. Management of gastric metastasis in SCLC typically involves a multidisciplinary approach. Systemic therapy, primarily chemotherapy, remains the cornerstone of treatment, with palliative care addressing symptoms and complications. Surgical intervention is usually reserved for specific cases requiring symptomatic relief. The prognosis for patients with gastric metastasis from SCLC is generally poor, reflecting the advanced stage of the disease. Median survival is significantly reduced compared to patients without gastric metastasis. This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.

Concordance of Whole-Slide Imaging and Conventional Light Microscopy for Assessment of Pathologic Response Following Neoadjuvant Therapy for Lung Cancer

Pathologic response is an endpoint in many ongoing clinical trials for neoadjuvant regimens, including immune checkpoint blockade and chemotherapy. Whole-slide scanning of glass slides generates high-resolution digital images and allows for remote review and potential measurement with image analysis tools, but concordance of pathologic response assessment on digital scans compared with that on glass slides has yet to be evaluated. Such a validation goes beyond previous concordance studies, which focused on establishing surgical pathology diagnoses, as it requires quantitative assessment of tumor, necrosis, and regression. Further, as pathologic response assessment is being used as an endpoint, such concordance studies have regulatory implications. The purpose of this study was 2-fold, which was as follows: first, to determine the concordance between pathologic response assessed on glass slides and that assessed on digital scans, and second, to determine if pathologists benefited from using measurement tools when determining pathologic response. To that end, hematoxylin and eosin–stained glass slides from 64 non–small cell lung carcinoma specimens were visually assessed for percent residual viable tumor (%RVT). The sensitivity and specificity for digital vs glass reads of pathologic complete response (0% RVT) and major pathologic response (≤10% RVT) were all >95%. When %RVT was considered as a continuous variable, the intraclass correlation coefficient of digital vs glass reads was 0.94. The visual assessments of pathologic response were supported by pathologist annotations of residual tumor and tumor bed areas. In a separate subset of hematoxylin and eosin–stained glass slides, several measurement approaches to quantifying %RVT were performed. Pathologist estimates strongly reflected measured %RVT. This study demonstrates the high level of concordance between glass slides evaluated using light microscopy and digital whole-slide images for pathologic response assessments. Pathologists did not require measurement tools to generate robust %RVT values from slide annotations. These findings have broad implications for improving clinical workflows and multisite clinical trials.

Homology modelling, molecular docking studies and synthesis of aminopyrimidines as inhibitors for deoxynucleoside kinase analogues in cancer chemoprevention

The development of alternative anticancer agents with minimal side effects has become more critical due to the rising recurrence of mammalian malignancies and the severe side effects of chemotherapeutic treatments. Kinases are an essential target for neostatic impact as they play an important role in the modulation of growth factor signalling. Our work aims to screen novel nine-series of thiazole-based aminopyrimidines and sulphaminopyrimidines against the enzymes mitochondrial thymidine kinase 2, deoxyguanosine kinase (2OCP), deoxycytidine kinase (2QRN) and thymidylate kinase (1E2Q) by molecular docking, synthesise and to study their in vitro inhibitory studies. The synthesised compounds were characterised by Infrared, Nuclear magnetic resonance and Mass spectroscopy. In silico studies, compound 4c stands out among the series, with a reported docking score ranging from −6 to −8 Kcal/mol against all the analogue kinases. The in vitro cytotoxicity assay against human small-cell lung carcinoma (A-549) has shown that 5c (IC50 = 53.9 µM) has an excellent cytotoxic effect over 4c (IC50= 68.68 µM). The reason might be the presence of the benzene sulphonamide group, which enhances their anticancer action. To conclude, the compounds 4c and 5c were found to be potent inhibitors of the deoxynucleoside kinases. In vivo studies must further verify these to prove their potent neostatic effect.