Purpose: The oncological outcomes of locally advanced cervical cancer (LACC) patients after treatment are poor and heterogeneous. This study aimed to determine the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) inflammatory index in predicting oncological outcomes in LACC patients. Patients and Methods: A total of 1588 LACC patients who received radiation therapy or concurrent chemoradiation were divided into training and test sets. Characteristics, survival, and a HALP cutoff determined by X-tile software were used to build predictive survival models on the training data. Validation of the model was performed on both sets. Results: Patients with a HALP score ≤ 22.2 tended to have lower age (p < 0.001), lower comorbidity rate (p = 0.016), lower body mass index (p < 0.001), higher stage (p < 0.001), larger tumor size (p < 0.001), and higher likelihood to receive radiation alone than concurrent chemoradiation (p < 0.001). Survival analysis demonstrated that HALP > 22.2 was independently associated with better progression-free survival (PFS; hazard ratio; HR 0.55) and overall survival (OS; HR 0.43). Validation of survival prediction by receiver-operating characteristics demonstrated a significantly improved area under the curve of survival prediction in both sets (p < 0.001) after the addition of the HALP index to the model. Conclusion: A lower HALP score was an independent predictive factor for poorer oncological outcomes. The addition of the HALP index can improve the accuracy of predicting the oncological outcomes of LACC patients.

Hanprasertpong J, et al. J Gynecol Oncol. 2017 Mar;28(4):e42. https://doi.org/10.3802/jgo.2017.28.e42

Three-dimensional (3D) cell culture models are used in cancer research because they mimic physiological responses in vivo compared with two-dimensional (2D) culture systems. Recently, cross-resistance of butyrate-resistant (BR) cells and chemoresistance in colorectal cancer (CRC) cells have been reported; however, effective treatments for BR cells have not been identified. In this study, we investigated the cytotoxicity of metformin (MET), an anti-diabetic drug, on BR CRC cells in a 3D spheroid culture model. The results demonstrate that MET decreases spheroid size, migration, and spheroid viability, while it increases spheroid death. The molecular mechanism revealed that AMP-activated protein kinase (AMPK) and Akt serine/threonine kinase 1(Akt) were significantly upregulated, whereas the acetyl-CoA-carboxylase (ACC) and mammalian target of rapamycin (mTOR) were downregulated, which led to caspase activation and apoptosis. Our findings show the potential cytotoxicity of MET on CRC-BR cells. The combination of MET and conventional chemotherapeutic drugs should be addressed in further studies to reduce the side effects of standard chemotherapy for CRC.

Background: The aim of this study was to determine the prognostic role of obesity on oncological outcomes, surgical complications, and postoperative morbidity of patients with early-stage cervical cancer. Methods: Between 2000 and 2016, we enrolled 500 patients with early-stage cervical cancer who underwent radical hysterectomy with pelvic node dissection (RHND) at Songklanagarind Hospital. For analysis, patients were divided based on their body mass index (BMI) into under-normal weight (<25 kg/m²), overweight (25–29.99 kg/m²), and obese (≥30 kg/m²) groups. Results: The median age was 47 years, and the median BMI was 24.3 kg/m² (25% quartile, 22.0 kg/m²; 75% quartile, 27.4 kg/m²). Patients in the obese and overweight groups were more likely to have comorbidities and adenocarcinoma than patients in the under-normal weight group. The median operative time (OT) was significantly longer in the obese and overweight groups than in the under-normal weight group. The 5-year recurrence-free survival (RFS) of the under-normal weight, overweight, and obese groups was 87.5, 86.2, and 97.6%, respectively, and the 5-year overall survival (OS) times were 95.8, 97.8, and 100%, respectively. There were no significant differences in RFS or OS among the 3 weight groups. Multivariate analysis did not identify BMI as a prognostic factor for RFS and OS. Conclusions: A high BMI was not associated with increased surgical complications or postoperative morbidity; furthermore, it was not associated with the prognosis of patients with early-stage cervical cancer after RHND. However, it was associated with adenocarcinoma and longer OT.

Cancer spheroids are spherical, three-dimensional (3D), in vitro assemblies of cancer cells, which are gaining importance as a useful model in cancer behavior studies. Designed to simulate key features of the in vivo tumor microenvironment, spheroids offer reliable insights for drug screening and testing applications. We observed contrasting phenotypes in 3D cervical cancer (CC) cultures. Thus, in this study, we compared the proteomes of 3D and traditional two-dimensional (2D) cultures of CC cell lines, HeLa, SiHa, and C33A. When cultured in in-house poly-(2-hydroxyethyl methacrylate)-coated plates under conditions suitable for 3D spheroid formation, these CC cell lines yielded spheroids exhibiting different features. Proteomic analysis of cells cultured in 2D and 3D cultures revealed similar protein profiles but remarkable differences in the expression levels of some proteins. In SiHa and C33A cells, the upregulation of key proteins required for spheroid formation was insufficient for the formation of compact spheroids. In contrast, HeLa cells could form compact spheroids because they upregulated the proteins, including cadherin-binding, cytoskeleton, and adhesion proteins, necessary for spheroid formation during the remodeling process. Overall, this study unravels the mechanisms underlying the formation of spheroids in the commonly used CC cell lines.

Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short‐chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growth and inducing apoptosis. However, microbiota studies have revealed an abnormally high abundance of butyrate‐producing bacteria in patients with CRC and indicated that it leads to chemoresistance. We characterized butyrate resistance in HCT‐116 and PMF‐K014 CRC cells after treatment with a maximum butyrate concentration of 3.2 mM. The 50% inhibitory concentration of butyrate was increased in butyrate‐resistant (BR) cells compared with that in parental (PT) cells. The mechanism of butyrate resistance was initially investigated by determining the expression of butyrate influx‐ and drug efflux‐related genes. We found the increased expression of influx‐ and efflux‐related genes in BR cells compared with that in PT cells. Proteomic data showed both identical and different proteins in PT and BR cells. Further analysis revealed the crossresistance of HCT‐116 cells to metformin and oxaliplatin and that of PMF‐K014 cells to 5‐fluorouracil. Our findings suggest that the acquisition of butyrate resistance induces the development of chemoresistance in CRC cells, which may play an important role in CRC development, treatment, and metastasis.