Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*

Programmed cell death 1 (PD-1) inhibitor therapy for lung adenocarcinoma may induce rare but severe hematologic adverse events, including severe anemia. Although glucocorticoids are recommended for managing immune-related adverse events, therapeutic experience with PD-1 inhibitor-induced severe anemia remains limited, and its efficacy and safety have not been fully validated. This article reports a case of advanced lung adenocarcinoma in which severe anemia developed following combination therapy with chemotherapy and PD-1 inhibitor. After comprehensive evaluation, the patient was diagnosed with anemia of inflammation (AI) and achieved significant hemoglobin recovery following high-dose glucocorticoid treatment. These findings may provide new insights into the recognition and management of this rare hematologic toxicity in clinical practice.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Anemia/etiology* ; Immunotherapy/adverse effects* ; Lung Neoplasms/immunology* ; Male ; Antibodies, Monoclonal/therapeutic use* ; Middle Aged

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections ; Gastritis/diagnosis* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy*

A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).
Male ; Humans ; Aged ; Pancreatic Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adenocarcinoma ; Neoplasm Recurrence, Local/surgery* ; Immunotherapy ; Liver Neoplasms/therapy* ; Pancreatectomy

A patient with advanced lung adenocarcinoma developed symptoms of frequent urination and urgent urination after 14 cycles of Pembrolizumab combined with chemotherapy. After making comprehensive analysis of the results of urine routine test, renal function, cystoscope and computed tomography (CT) examination, immune checkpoint inhibitors related cystoureteritis and acute kidney injury were considered. The patient's symptoms were relieved after discontinuation of Pembrolizumab combined with chemotherapy. However, the symptoms of urinary irritation worsened significantly after rechallenging Pembrolizumab combined with chemotherapy, and the symptoms was relieved after corticosteroids treatment. If patients develop urinary symptoms during immune checkpoint inhibitors treatment, immune checkpoint inhibitors related cystoureteritis should be considered for early differential diagnosis in order to implement appropriate treatment.
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Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/pathology* ; Adenocarcinoma of Lung/drug therapy* ; Tomography, X-Ray Computed

Esophageal cancer (EC) has a high incidence and poor prognosis. The two major histological types, squamous cell carcinoma and adenocarcinoma, differ in their epidemiology and treatment options. Patients with locally advanced EC benefit from multimodal therapy concepts including neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy, and perioperative chemotherapy. Currently, immunotherapy for the solid tumor is a hot spot. Treatment with adjuvant immune checkpoint inhibitors (ICIs) is the first immunotherapy for resectable EC listed in the latest National Comprehensive Cancer Network Guidelines for the Esophageal and Esophagogastric Junction Cancers. Recent clinical trials have established ICIs for three treatment models of resectable EC. Their short-term results demonstrated ideal efficacy and tolerable toxicity, though some concerns remain. This review summarizes the novel data on the ICIs for resectable EC and lists the registered related clinical trials. Hopefully, this review can provide a reference for ongoing research on the treatment options for resectable EC.
Humans ; Esophageal Neoplasms/pathology* ; Esophagogastric Junction/pathology* ; Neoadjuvant Therapy/methods* ; Adenocarcinoma/drug therapy* ; Immunotherapy

BACKGROUND: Acquired and primary resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is still the bottleneck of clinical treatment of advanced non-small cell lung cancer (NSCLC). STE029 is a novel anticancer drug which consists of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) inhibitor and novel cancer cell membrane targeting molecular. This study aimed to investigate the reversal mechanism of EGFR-TKI resistance by STE029 in lung adenocarcinoma. METHODS: CCK8 test was used to test the cell viability and survival rate of EGFR mutated PC9 cell (Gefitinib sensitive), PC9/BB4 cell (acquired Gefitinib resistant), and EGFR wild type A549 cell after treatment of STE029, Gefitinib or combination of both. EdU test was applied to detect changes in cell cycle and Hoechst 33258 was applied to detect apoptosis rate in overcoming the EGFR-TKI resistance. The activity of EGFR/PI3K/Akt, cell cycle and apoptosis signal pathways were examined. In vivo, nude mice were exposed to STE029, Gefitinib and STE029+Gefitinib for 5 wk. And the the tumor volume was measured and tumor weight was obtained on the last day. RESULTS: (1) PC9 cells was highly sensitive to Gefitinib, while PC9/BB4 and A549 cell showed significant resistance to Gefitinib treatment; (2) STE029+Gefitinib treatment could significantly decrease the 50% inhibitory concentrarion (IC₅₀) of Gefitinib in PC9, PC9/BB4 and A549 cells (P<0.05, respectively); (3) In PC9 and PC9/BB4 cells, STE029+Gefitinib can block cell cycle and inhibit cell proliferation (P<0.001), while there was no significant difference in apoptosis rate among three drug intervention groups (P>0.05); However, apoptosis rate was increased in STE029+Gefitinib group in A549 cell (P<0.01), while no significance detected in cell proliferation (P>0.05). (4) In PC9 and PC9/BB4 cells, the combination of STE029 and Gefitinib could downregulate p-EGFR, p-Akt, p-Cyclin D1 and Cyclin D1 (P<0.001), and upregulate the expression of GSK-3β (P<0.001), and the expression of cleaved caspase-8, caspase-8 cleaved caspase-9, caspase-9 showed no difference among groups (P>0.05). In A549 cells, the combination of STE029 and Gefitinib could downregulate p-Akt (P<0.001) and upregulate cleaved caspase-8 and cleaved caspase-9 (P<0.001); (5)In vivo, the combination of STE029 and Gefitinib effectively inhibited tumor development and progression compared to STE029 alone or Gefitinib alone, with significant difference (P<0.05) in PC9 and PC9/BB4 xenografted tumor. CONCLUSIONS STE029 could sensitize Gefitinib by inhibiting EGFR/PI3K/Akt pathway, blocking the tumor cell cycle and proliferation and inducing apoptosis through caspase-8 and caspase-9 dependent pathway. STE029 deserves further investigations in overcoming EGFR-TKI resistance in lung cancer.
Animals ; Mice ; Humans ; Gefitinib/pharmacology* ; Caspase 9 ; Caspase 8 ; Cyclin D1 ; Carcinoma, Non-Small-Cell Lung ; Glycogen Synthase Kinase 3 beta ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/drug therapy* ; Protein Kinase Inhibitors/pharmacology* ; ErbB Receptors/genetics*

Objective: To investigate the clinicopathological features of early gastric cancers after Helicobacter pylori (H. pylori) eradication. Methods: The clinical data of 26 cases of gastric cancer that were diagnosed after H. pylori eradication and 45 cases without H. pylori eradication in the 989 Hospital of the Joint Logistics Support Force of the People's Liberation Army (the former 152 Hospital), Pingdingshan, China from 2013 to 2021 were collected. The histological, immunophenotypic and clinical characteristics of the two groups were compared, and discussed with review of the related literature. Results: Among the gastric cancer patients with H. pylori eradication, there were 20 males and 6 females with a median age of 65 years (range 53 to 77 years). The cancer involved the upper part of the stomach in 12 cases, the middle part of the stomach in 4 cases, and the lower part of the stomach in 10 cases. The median diameter of the tumors was 12 mm (range 4-29 mm). According to the Paris Classification, 4 cases were 0-Ⅱa, 4 cases were 0-Ⅱb, 18 cases were 0-Ⅱc. White light endoscopy showed that the lesions were reddish to yellowish. The lesion boundary was clear in 12 cases and was unclear or gastritis-like changes in 14 cases, while the irregular microvascular structure and microsurface structure, as well as the relatively visible spinous boundary, were visible under narrow-band imaging. There were 20 cases of well-differentiated tubular adenocarcinoma, 4 cases of highly to moderately differentiated tubular adenocarcinoma, and 2 cases of well-differentiated tubular adenocarcinoma with papillary adenocarcinoma. Compared with gastric cancers without H. pylori eradication, gastric cancers diagnosed after H. pylori eradication was associated with lower nucleus-cytoplasm ratio (<50%), normal epithelial coverage on the cancer surface, mild atypical epithelial coverage on the cancer surface, elongation of non-cancerous glands in the cancer tissue and subepithelial progression of cancerous glands were higher (P<0.05). The cellular immunophenotypes were gastric type in 6 cases, intestinal type in 4 cases and gastrointestinal mixed type in 16 cases. Conclusions: The early gastric cancers diagnosed after H. pylori eradication are more subtle clinically and mostly well-differentiated tubular adenocarcinoma. The important morphological features of gastric cancer diagnosed after H. pylori eradication are decreased cytological atypia and overlying normal epithelium or mildly atypical epithelium of the cancer. Understanding and recognizing these morphological features are helpful to make correct endoscopic and pathological diagnoses.
Adenocarcinoma/pathology* ; Aged ; Female ; Gastric Mucosa/pathology* ; Helicobacter Infections/drug therapy* ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Stomach Neoplasms/drug therapy*

Cancer is one of the most devastating diseases worldwide and definitive therapeutics for treating cancer are not yet available despite extensive research efforts. The key challenges include limiting factors connected with traditional chemotherapeutics, primarily drug resistance, low response rates, and adverse side-effects. Therefore, there is a high demand for novel anti-cancer drugs that are both potent and safe for cancer prevention and treatment. Gallic acid (GA), a natural botanic phenolic compound, can mediate various therapeutic properties that are involved in anti-inflammation, anti-obesity, and anti-cancer activities. More recently, GA has been shown to exert anti-cancer activities via several biological pathways that include migration, metastasis, apoptosis, cell cycle arrest, angiogenesis, and oncogene expression. This review discusses two aspects, one is the anti-cancer potential of GA against different types of cancer and the underlying molecular mechanisms, the other is the bibliometric analysis of GA in cancer and tumor research. The results indicated that lung cancer, prostate cancer, stomach cancer, and colon adenocarcinoma may become a hot topic in further research. Overall, this review provides evidence that GA represents a promising novel, potent, and safe anti-cancer drug candidate for treating cancer.
Adenocarcinoma/drug therapy* ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Cell Line, Tumor ; Colonic Neoplasms ; Gallic Acid/therapeutic use* ; Humans ; Male