Evaluate the value of prolonging the duration of tiopronin for injection administration in preventing hepatotoxicity.

As part of supportive therapy, prophylaxis with tiopronin for injection (TI) against common hepatotoxicity complications has often been used. However, methods to prevent hepatotoxicity have not been established. Therefore, our study was aimed to find out the relationship between the periods of TI prophylaxis and post-treatment hepatotoxicity, and evaluated the value of prolonging the duration of TI administration in preventing hepatotoxicity. Hepatotoxicity was detected through liver transaminases, bilirubin, alkaline phosphatase, and clinical features of liver insufficiency. Multivariable logistic regressions were conducted to examine the association of the periods of TI prophylaxis and post-treatment hepatotoxicity. Between January 2022 and March 2023, a total of 452 patients with gynecological cancer were enrolled in the study, of which 93 (20.58%) participants were post-treatment hepatotoxicity positive. TI with different prevention days were no significant difference among participants with or without post-treatment hepatotoxicity in crude model (P > 0.05). The P-value, the odds ratios (OR) and 95% confidence intervals (CI) of participants with TI prophylaxis for 1 day for post-treatment hepatotoxicity were 0.040, 3.534 (1.061-11.765) in fully adjusted model. Past history of hepatotoxicity is a confounding variable, and there was no significant difference for post-treatment hepatotoxicity when stratified by past history of hepatotoxicity (P > 0.05). The study indicate that the periods of TI prophylaxis is not associated with post-treatment hepatotoxicity, suggesting that prolonged the periods of TI prophylaxis might be an invalid method for the prevention of post-treatment hepatotoxicity.

Risk factors for postoperative infections in esophageal tumor patients.

Postoperative infections (PI) are a serious complication after esophageal cancer surgery, as they might be correlated with an elevated risk of death. While several reports discuss risk factors for PI in esophageal tumor surgery, there is a limited amount of research on overall postoperative infections. Therefore, investigating the factors that influence PI holds great clinical significance. We retrospectively reviewed surgical data from a cohort of 902 patients diagnosed with esophageal tumors. The study included esophageal cancer patients treated in the Department of Thoracic Surgery at Anyang Tumor Hospital from January to December 2021. Preoperative and operative risk factors for PI were evaluated using univariable and multivariable analyses. The overall incidence of PI was 28.3% (255/902). Multivariable logistic regression analysis revealed that smoking and preoperative hospital stays are significant risk factors for PI after esophageal tumor surgery. Smoking and preoperative hospital stays are identified as risk factors for PI following esophageal tumor surgery. Based on our results, we predict that certain groups of patients may have a higher risk of PI following esophageal tumor surgery. Preventive measures or closely monitor of these patients may be required to reduce the incidence of postoperative PI.

[Comparative study of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on cell differentiation in lewis lung cancer].

Coptidis Rhizoma and Aconiti Kusnezoffii Radix represent hot Chinese medicine and cold Chinese medicine respectively. The purpose of this study is to observe the differentiation effect of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on lewis lung cancer and compare effect of hot Chinese medicine and cold Chinese medicine on tumor progression. In this study, the rat serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix was prepared to treat lewis lung cancer cells in vitro, and effects of the serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix on cell differentiation, proliferation, adhesion, succinic dehydrogenase (SDH) activity and gap-junction intercellular communication (GJIC) were investigated. In vivo, the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of coptis chinensis or aconite by intragastric administration bid for four weeks, and the influences of coptis chinensis and aconite on tumor progression were evaluated by body temperature, blood oxygen saturation, red cell ATPase, blood rheology, intratumor hypoxia, capillary permeability and GJIC. The results showed that the serum containing aconite could induce cell differentiation, inhibit cell proliferation and migration, promote SDH activity and GJIC in lewis lung cancer cells. The serum containing Coptidis Rhizoma increased cell adhesion and decreased SDH activity and GJIC without cell differentiation although it also suppressed cell proliferation. Aconiti Kusnezoffii Radix water decoction could keep body temperature, blood oxygen saturation, red cell ATPase and blood rheology, and improve intratumor hypoxia, capillary permeability and GJIC in tumor bearing mice, which led to slower tumor growth and less metastasis. Coptidis Rhizoma water decoction decreased body temperature, blood oxygen saturation, red cell ATPase, blood rheology and GJIC, and promoted intratumor hypoxia and capillary permeability, which resulted to more tumor metastasis although it also prevented tumor growth. These results suggested that the hot Chinese medicine could induce tumor cell differentiation and prevent tumor poison invagination, which is better for tumor treatment than cold Chinese medicine.

The combination of TRPM8 and TRPA1 expression causes an invasive phenotype in lung cancer.

Our recent studies have shown that hypothermic microenvironment promotes tumor progression and that the molecular sensors for cold are the transient receptor potential (TRP) channels TRPM8 and TRPA1. To evaluate the contribution of TRPM8 and TRPA1 to cancer malignancy, we screened cell subpopulations from Lewis lung cancer (LLC) using limiting dilutions and Western blotting. We identified that LLC-1 cells express 3-fold more TRPM8 than TRPA1, LLC-2 cells express TRPM8 at levels similar to TRPA1, and LLC-3 cells express TRPM8 at one-third the level of TRPA1. LLC-2 cells showed greater adhesion, migration, invasiveness and resistance to hypothermia than LLC-1 and LLC-3 cells, although LLC-2 cells had a longer doubling time. TRPM8 or TRPA1 knockdown using siRNA promoted cell proliferation and decreased adhesion and invasiveness in LLC-2 cells. When assessed for UCP2 staining, LLC-1 cells showed increased staining compared to LLC-2 cells, both of which had more UCP2-positive cells than the LLC-3 subpopulation. In an autophagy assay, hypothermia induced substantially less autophagy in LLC-1 cells than in LLC-2 cells, which displayed decreased autophagy compared to LLC-3 cells. Moreover, mice injected with LLC-2 cells had significantly more spontaneous and experimental lung metastases and a shorter overall survival time than mice injected with LLC-1 or LLC-3 cells. Importantly, LLC-2 cells were also more resistant to activated spleen CTL and the chemotherapeutic drug doxorubicin than LLC-1 and LLC-3 cells in vitro. Collectively, our data suggest that TRPM8 induces UCP2 to trigger metabolic transformation, whereas TRPA1 induces autophagy during adverse conditions, and the combination of both genes contributes directly to an invasive phenotype in lung cancer.

Hypothermia activates adipose tissue to promote malignant lung cancer progression.

Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B) to methylnitrosourea (MNU) caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC) metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT) and protects the tumor cell against immune control by TGF-ß1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression.