ABSTRACT

Papillary adenocarcinoma (PA) of the lung is a specific form of lung cancer characterized by papillary structures in tumor cells. This type of cancer is relatively rare and has distinct pathological and radiological features that differentiate it from other types of lung adenocarcinomas. Determining the specific subtype of adenocarcinoma is a crucial factor in the choice of chemotherapy treatment. Detecting PA is fundamental, as it has both prognostic and therapeutic implications for patients with lung carcinoma. In this paper, we discuss two cases of young patients diagnosed with PA of the lung. The cases we present are particularly intriguing due to the relatively young age of the patients.

PMID:37809161 | PMC:PMC10560075 | DOI:10.7759/cureus.44838

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PubMed articles on: Cardio-Oncology

Alterations in Left Atrial Strain in Breast Cancer Patients Immediately Post Anthracycline Exposure

Heart Lung Circ. 2023 Oct 6:S1443-9506(23)04291-9. doi: 10.1016/j.hlc.2023.06.864. Online ahead of print.

ABSTRACT

AIMS: With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction.

METHODS: This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured.

RESULTS: All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LASRES 34.8% vs 31.5%, p<0.001)CD 17.2% vs 14.4%, p<0.001)RES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%).

CONCLUSIONS: LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC.

PMID:37806911 | DOI:10.1016/j.hlc.2023.06.864

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PubMed articles on: Cardio-Oncology

Deep learning-assisted high-content screening identifies isoliquiritigenin as an inhibitor of DNA double-strand breaks for preventing doxorubicin-induced cardiotoxicity

Biol Direct. 2023 Oct 9;18(1):63. doi: 10.1186/s13062-023-00412-7.

ABSTRACT

BACKGROUND: Anthracyclines including doxorubicin are essential components of many cancer chemotherapy regimens, but their cardiotoxicity severely limits their use. New strategies for treating anthracycline-induced cardiotoxicity (AIC) are still needed. Anthracycline-induced DNA double-strand break (DSB) is the major cause of its cardiotoxicity. However, DSB-based drug screening for AIC has not been performed possibly due to the limited throughput of common assays for detecting DSB. To discover new therapeutic candidates for AIC, here we established a method to rapidly visualize and accurately evaluate the intranuclear anthracycline-induced DSB, and performed a screening for DSB inhibitors.

RESULTS: First, we constructed a cardiomyocyte cell line stably expressing EGFP-53BP1, in which the formation of EGFP-53BP1 foci faithfully marked the doxorubicin-induced DSB, providing a faster and visible approach to detecting DSB. To quantify the DSB, we used a deep learning-based image analysis method, which showed the better ability to distinguish different cell populations undergoing different treatments of doxorubicin or reference compounds, compared with the traditional threshold-based method. Subsequently, we applied the deep learning-assisted high-content screening method to 315 compounds and found three compounds (kaempferol, kaempferide, and isoliquiritigenin) that exert cardioprotective effects in vitro. Among them, the protective effect of isoliquiritigenin is accompanied by the up-regulation of HO-1, down-regulation of peroxynitrite and topo II, and the alleviation of doxorubicin-induced DSB and apoptosis. The results of animal experiments also showed that isoliquiritigenin maintained the myocardial tissue structure and cardiac function in vivo. Moreover, isoliquiritigenin did not affect the killing of HeLa and MDA-MB-436 cancer cells by doxorubicin and thus has the potential to be a lead compound to exert cardioprotective effects without affecting the antitumor effect of doxorubicin.

CONCLUSIONS: Our findings provided a new method for the drug discovery for AIC, which combines phenotypic screening with artificial intelligence. The results suggested that isoliquiritigenin as an inhibitor of DSB may be a promising drug candidate for AIC.

PMID:37807075 | PMC:PMC10561451 | DOI:10.1186/s13062-023-00412-7

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PubMed articles on: Cancer & VTE/PE

Accuracy of the ACS NSQIP Surgical Risk Calculator for Predicting Postoperative Complications in Gastric Cancer Following Open Gastrectomy

Am Surg. 2023 Oct 12:31348231206581. doi: 10.1177/00031348231206581. Online ahead of print.

ABSTRACT

INTRODUCTION: The prediction of complications before gastric surgery is of utmost importance in shared decision making and proper counseling of the patient in order to minimize postoperative complications. Our aim was to evaluate the predictive validity of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk calculator in gastric cancer patients who underwent gastrectomy.

METHODS: Preoperative assessment data of 432 patients were retrospectively reviewed and manually entered into the calculator. The accuracy of the calculator was evaluated using Pearson's chi-squared test, C-statistic, Brier score, and Hosmer-Lemeshow test.

RESULTS: The lowest Brier scores were observed in urinary tract infection, renal failure, venous thromboembolism, pneumonia, and cardiac complications. Best results were obtained for predicting sepsis, discharge to rehabilitation facility, and death (low Brier scores, C-statistic >.7, and Hosmer-Lemeshow P > .05).

CONCLUSION: The calculator had a strong performance in predicting sepsis, discharge to the rehabilitation facility, and death. However, it performed poor in predicting the most commonly observed events (any or serious complication and surgical site infection).

PMID:37823864 | DOI:10.1177/00031348231206581

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PubMed articles on: Cardio-Oncology

Inhibiting mir-34a-5p regulates doxorubicin-induced autophagy disorder and alleviates myocardial pyroptosis by targeting Sirt3-AMPK pathway

Biomed Pharmacother. 2023 Oct 6;168:115654. doi: 10.1016/j.biopha.2023.115654. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a commonly used chemotherapy drug widely applied in various cancers such as breast cancer, leukemia, and sarcomas. However, its usage is limited by cardiotoxicity. Additionally, the cardiac toxicity of DOX accumulates with dose and duration, making it imperative to identify therapeutic targets for DOX-induced cardiomyopathy (DIC). It has been reported that miRNAs are involved in the progression of DIC. Mir-34a-5p has been identified as an early diagnostic marker for DIC. While studies have shown the involvement of mir-34a-5p in DIC apoptosis, it has not been validated in animal models, nor has the potential improvement of DIC by inhibiting mir-34a-5p been confirmed. Autophagy and pyroptosis are key factors in the development of DIC and can serve as therapeutic targets for its treatment. In this study, we found that mir-34a-5p was upregulated in the heart after DOX treatment and that the inhibition of mir-34-5p reduced autophagy and pyroptosis in DIC. We also found that the inhibition of mir-34a-5p inhibited pyroptosis by regulating autophagy and reducing mitochondrial reactive oxygen species. Moreover, we identified Sirtuin3 (Sirt3) as a target gene of mir-34a-5p using a double-luciferase reporter assay. overexpression Sirt3 reduced pyroptosis by alleviating autophagy. Our research findings suggest that inhibiting mir-34a-5p has a beneficial role in alleviating autophagy and pyroptosis in DIC. This provides therapeutic prospects for treating DIC.

PMID:37806095 | DOI:10.1016/j.biopha.2023.115654

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PubMed articles on: Cardio-Oncology

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer

Cardiovasc Toxicol. 2023 Oct 7. doi: 10.1007/s12012-023-09807-4. Online ahead of print.

ABSTRACT

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

PMID:37804372 | DOI:10.1007/s12012-023-09807-4

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PubMed articles on: Cancer & VTE/PE

Risk of Thrombosis and Bleeding in Gynecologic Cancer Surgery: Systematic Review and Meta-Analysis

Am J Obstet Gynecol. 2023 Oct 10:S0002-9378(23)00735-4. doi: 10.1016/j.ajog.2023.10.006. Online ahead of print.