Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.
Background Bariatric surgery is the most effective therapy for obesity, but targeted weight reduction is not always achieved. Serum lipocalin-2 (LCN2) is closely associated with obesity, but its impact on weight loss after surgery is unknown. We aimed to access the reliability of LCN2 levels and other parameters as effective predictors of excellent weight loss (≥ 75% excess weight loss (EWL)) 1 year after bariatric surgery. Methods This retrospective study evaluated 450 patients (aged 18–65 years) with obesity at 3 months and 1 year after laparoscopic sleeve gastrectomy (LSG) surgery. Seventy-four patients who underwent LSG surgery and met the inclusion and exclusion criteria were included in this study. Serum LCN2, thyroid function, and metabolic and anthropometric parameters were assessed. Weight reduction was expressed as %EWL and percent total weight loss (%TWL) at 3 months and 1 year post surgery. Multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate predictors of ≥ 75%EWL. Results In our cohort, %EWL and %TWL were both strongly associated with preoperative serum LCN2 levels. The binary logistic regression analysis showed that preoperative LCN2, waist circumference, and glycated hemoglobin were independent predictors of excellent weight loss. Conclusions Based on these results, we determined a new P index with better predictive value for excellent weight reduction (≥ 75%EWL) 1 year after LSG surgery. Graphical abstract
As new screening tools for sarcopenia, the serum sarcopenia index (SI) and creatinine/cystatin C ratio (CCR) had not been confirmd in a population with a high fragility fracture risk. This study aimed to evaluate whether SI and CCR indicators are useful for diagnosing sarcopenia and to determine their prediction values for future falls and fractures. A total of 404 hospitalized older adults were enrolled in this longitudinal follow-up study (mean age = 66.43 ± 6.80 years). The receiver operating curve (ROC) was used to assess the diagnostic accuracy of SI and CCR. Backward-selection binary logistic regression was applied to develop the optimal models for the diagnosis of new falls and fractures. SI had a significantly higher area under the curve (AUC) than CCR for predicting sarcopenia. The optimal models had acceptable discriminative powers for predicting new falls and fractures. Lower SI and CCR are the independent risks for sarcopenia, new falls, and fractures in the low-BMD population. SI and CCR, as easily accessible biochemical markers, may be useful in the detection of sarcopenia and in predicting the occurrence of new falls and fractures in patients with low BMD who have not previously experienced falls or fractures. However, further external validations are required.
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