Κυριακή 14 Νοεμβρίου 2021

Sensitization of breast cancer to Herceptin by redox active nanoparticles

xlomafota13 shared this article with you from Inoreader

Am J Cancer Res. 2021 Oct 15;11(10):4884-4899. eCollection 2021.

ABSTRACT

Herceptin-resistant tumor relapse remains a major clinical issue responsible for the poor prognosis of HER2+ breast cancer. Understanding the underlying mechanisms and finding a therapeutic solution are of paramount urgency to improve the patient management. Here we report that anticancer redox active cerium oxide nanoparticles (CONPs) can potently sensitize the cancer cells to the cytotoxicity of Herceptin. By comparing between Herceptin-sensitive and Herceptin-resistant human breast cancer cell lines under normoxic as well as hypoxic culture conditions, we found that in the presence of CONPs, Herceptin can kill the Herceptin-resistant cells equally effectively as it kills the Herceptin-sensitive cells under the hypoxic, but not normoxic, culture conditions by inhibiting the cell viability, survival and proliferation. Signaling analysis reveals that u nder the normoxic conditions, the levels of hypoxia induced factor 1α as well as vascular endothelial growth factor are higher in the Herceptin-resistant cells than that in the Herceptin-sensitive cells and are strongly induced once the culture is switched to the hypoxic conditions, which can be potently suppressed by CONPs. Treatment with CONPs plus Herceptin significantly slows down the primary tumor growth and lung metastasis of the Herceptin-resistant cells in a xenograft mouse model of orthotopic breast cancer through inhibiting the cell proliferation and survival as well as tumor angiogenesis. These results shed new lights on the mechanisms underlying the Herceptin resistance of the HER2+ breast cancer and provide insights into introducing CONPs-like agents to Herceptin-based therapy to improve treatment outcomes.

PMID:34765298 | PMC:PMC8569362

View on the web

Effect of exercise on peritoneal microenvironment and progression of ovarian cancer

xlomafota13 shared this article with you from Inoreader

Am J Cancer Res. 2021 Oct 15;11(10):5045-5062. eCollection 2021.

ABSTRACT

Ovarian cancer is one of the deadliest gynecological malignancies and lacks treatments that do not significantly impact patient health-related quality of life. Exercise has been associated with reduced cancer risk and improved clinical outcomes; however the underlying molecular mechanisms are unknown. In this study, we utilized a treadmill-running exercise model to investigate the effects of exercise on high-grade serous ovarian carcinoma (HGSOC) progression and chemotherapy outcomes. We found that treadmill-running suppressed peritoneal colonization of tumors in a syngeneic mouse ovarian cancer model. Acute exercise stimulated the production of CCL2 and IL-15 in the peritoneal microenvironment while downregulating CCL22, VEGF, and CCL12. Using a co-culture model, we demonstrated the role of CCL2 in mediating the activity of peritoneal cells to inhibit cancer cel l viability. We showed that the activation of M1 macrophages may contribute to the exercise-induced changes in the peritoneal microenvironment. We identified that chronic exercise modulates gene expression of intraperitoneal fat tissues related to lipid formation, thermogenesis, browning, and inflammation, which can contribute to inhibiting the colonization of metastatic ovarian cancer. Treadmill running also lowered blood urea nitrogen levels and reduced incidence of neutropenia and thrombocytopenia during chemotherapy in a mouse model, suggesting the potential beneficial effects of exercise in improving chemotherapy outcomes. Our data provided new insights into the acute and chronic effects of physical activity on ovarian cancer at the molecular and in vivo levels.

PMID:34765311 | PMC:PMC8569339

View on the web

Identification of potential immune-related circRNA-miRNA-mRNA regulatory network in cutaneous squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader

Am J Cancer Res. 2021 Oct 15;11(10):4826-4843. eCollection 2021.

ABSTRACT

Circulating RNAs (circRNAs) are involved in tumor development and progression by participating in immune regulation. Nevertheless, the circRNAs expression profiles and their roles on the immunomodulatory effects in cutaneous squamous cell carcinoma (cSCC) have rarely been studied. In our study, we identified the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), mRNAs (DEmRNAs) in cSCC and established the circRNA competing endogenous RNAs (ceRNAs) network. Subsequently, the hub differentially expressed immune-related genes were identified and validated by immunochemistry as well as the GO and KEGG pathway analysis were performed. 54 differentially expressed circRNAs were identified and hub differentially expressed immune-related genes were identified and they were mostly associated with immune response in the progression of cSCC. Our results indic ated that the potential immune-related circRNA-miRNA-mRNA network may assist in understanding the molecular mechanisms underlying the carcinogenesis and progression in cSCC. Moreover, the immune-related genes may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets for cSCC patients.

PMID:34765295 | PMC:PMC8569358

View on the web

Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader

Abstract

Background

Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC).

Methods

A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical-demographic data, BMI, and outcomes.

Results

HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3-year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI.

Conclusions

Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.

View on the web

Medical analysis of the contribution of sialendoscopy in managing non-tumoral main salivary gland pathology in Reunion Island: Observational study following STROBE guidelines

xlomafota13 shared this article with you from Inoreader

Eur Ann Otorhinolaryngol Head Neck Dis. 2021 Nov 9:S1879-7296(21)00253-2. doi: 10.1016/j.anorl.2021.10.005. Online ahead of print.

ABSTRACT

GOALS: To perform a medical analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory.

MATERIAL AND METHOD: A multicenter retrospective observational study was conducted for an 8-year period, before and after introduction of sialendoscopy (2011-2014 and 2015-2018), following STROBE guidelines.

OBJECTIVES: To compare populations treated before (period A) and after (period B) the introduction of sialendoscopy in terms of clinical characteristics, and analyze the characteristics of patients treated by sialendoscopy.

RESULTS: Two hundred and sixty-five patients were included: 74 in 2011-2014 and 191 in 2015-2018; 139 had sialendoscopy. Populations A and B were comparable except for the proportion of parotids treated (9% vs. 31%, respectively; P<0.0001), and smaller stones (11mm vs. 7.4mm, respectively; P=0.003). One hundred and ten pure sialendoscopies and 29 combined routes (20.8%) were performed: 63% submandibular and 37% parotid. Median age was 46 years. The M/F sex ratio was 0.96. Thirty-seven patients presented stenosis. There were 10 cases of papillary catheterization failure (7.1%), and 16 false routes or creation of false channels (11.5%), including 9 during the learning period. The rate of crossover to gland resection decreased: 10.45% for 2015-2016 and 5.56% for 2017-2018.

CONCLUSION: Although follow-up ranged between 12 and 55months (median, 30months), sialendoscopy appeared to be a useful and reliable technique, with a role in therapeutic strategy for the management of non-tumoral salivary pathologies in Reunion Island.

PMID:34772641 | DOI:10.1016/j.anorl.2021.10.005

View on the web

Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck

xlomafota13 shared this article with you from Inoreader

Eur Arch Otorhinolaryngol. 2021 Nov 12. doi: 10.1007/s00405-021-07162-0. Online ahead of print.

ABSTRACT

BACKGROUND: Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common.

METHODS: This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival.

RESULTS: The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS.

CONCLUSIONS: Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.

PMID:34773167 | DOI:10.1007/s00405-021-07162-0

View on the web

Open wound management following pull‐through resection for oral cancer: A case series of 14 patients

xlomafota13 shared this article with you from Inoreader

Abstract

●Following pull-through resection for oral cancer, primary closure of the oral defect is sometimes difficult. Incompletely closed defects may result in surgical site infection (SSI). ●We investigated the occurrence of SSI during and after open wound management following pull-through resection, other surgical outcomes, and postoperative quality of life (QOL). ●Open wound management was performed when the resection range was preoperatively expected to be half or less of the tongue and the defect was difficult to close primarily. ●The defect was left open, and drains were placed through the defect. The wound was cleansed after surgery, and the drains were removed as the wound healed. ●Open wound management was a simple and safe method with no occurrence of SSI. Postoperative QOL was acceptable when the oral defects were contained within half of the mobile tongue or less than half of the tongue base.

View on the web