Αναζήτηση αυτού του ιστολογίου

Τρίτη 20 Οκτωβρίου 2020

Inducing multiple antibodies to treat squamous cell esophageal carcinoma

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Abstract

Background

The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction.

Methods

Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70.

Results

Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis.

Conclusions

The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.

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Ovarian cancer cells direct monocyte differentiation through a non-canonical pathway

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Abstract

Background

Alternatively-activated macrophages (AAMs), an anti-inflammatory macrophage subpopulation, have been implicated in the progression of high grade serous ovarian carcinoma (HGSOC). Increased levels of AAMs are correlated with poor HGSOC survival rates, and AAMs increase the attachment and spread of HGSOC cells in vitro. However, the mechanism by which monocytes in the HGSOC tumor microenvironment are differentiated and polarized to AAMs remains unknown.

Methods

Using an in vitro co-culture device, we cultured naïve, primary human monocytes with a panel of five HGSOC cell lines over the course of 7 days. An empirical Bayesian statistical method, EBSeq, was used to couple RNA-seq with observed monocyte-derived cell phenotype to explore which HGSOC-derived soluble factors supported differentiation to CD68+ macrophages and subsequent polarization towards CD163+ AAMs. Pathways of interest were interrogated using small molecule inhibitors, neutralizing antibodies, and CRISPR knockout cell lines.

Results

HGSOC cell lines displayed a wide range of abilities to generate AAMs from naïve monocytes. Much of this variation appeared to result from differential ability to generate CD68+ macrophages, as most CD68+ cells were also CD163+. Differences in tumor cell potential to generate macrophages was not due to a MCSF-dependent mechanism, nor variance in established pro-AAM factors. TGFα was implicated as a potential signaling molecule produced by tumor cells that could induce macrophage differentiation, which was validated using a CRISPR knockout of TGFA in the OVCAR5 cell line.

Conclusions

HGSOC production of TGFα drives monocytes to differentiate into macrophages, representing a central arm of the mechanism by which AAMs are generated in the tumor microenvironment.

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Presence of dynapenia and association with anthropometric variables in cancer patients

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Abstract

Background

Dynapenia is defined as an age-related loss of muscle strength. There is little information on dynapenia in cancer patients and on how it relates to anthropometric variables. The aim of this study was to analyze the presence of dynapenia and its association with anthropometric variables in hospitalized cancer patients.

Methods

Participants comprised adult and elderly cancer patients evaluated within the first 48 h of hospital admission to a tertiary public hospital, a referral center for gastrointestinal tract surgery. Anthropometric variables were measured according to standardized protocols. Dynapenia was identified based on handgrip strength (HGS), according to the cutoff points defined by the European Working Group on Sarcopenia in Older People (EWGSOP2), with values for women < 16 kg and for men < 27 kg. Statistical analysis was performed using SPSS software, version 22.0, with a significance level of 5%.

Results

This study included 158 patients aged in average 59.5 ± 14.0 years; of these, 53.6% were elderly, 58.9% non-white and 59.5% had some degree of malnutrition. The most prevalent type of cancer was that of the lower gastrointestinal tract (33.5%). The presence of dynapenia was observed in 23.4% of the patients and cachexia in 36.1%. There was an association between dynapenia with age (p < 0.001), life stage (p = 0.002) and race/color (p = 0.027), and also with body mass index (BMI) (p = 0.001) and adductor pollicis muscle thickness (APMT) of both hands (p < 0.05). After logistic regression analysis, adjusted for the sociodemographic variables, the APMT of the dominant hand and the low weight determined by body mass index remained associated with the occurrence of dynapenia (p < 0.05).

Conclusions

In this study we confirmed that dynapenia was present in cancer patients, being associated with APMT of the dominant hand and low weight. HSG was proven to be a reliable and complementary measure to be added to the process of assessing nutritional status, contributing to the nutritional diagnosis of these patients and to the detection of early muscle depletion.

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A Swedish Nationwide prospective study of oncological and reproductive outcome following fertility-sparing surgery for treatment of early stage epithelial ovarian cancer in young women

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Abstract

Background

Epithelial ovarian cancer (EOC) is rare in women of reproductive age and fertility-sparing surgery (FSS) may be applied in early stages. The purpose of this study was to investigate the safety and efficacy of FSS for treatment of EOC.

Methods

The Swedish nationwide population-based Quality Register for Gynecological Cancer was used to identify all women 18–40 years of age diagnosed with stage I EOC between 2008 and 2015. Detailed data on surgery, staging, histopathology, and follow-up were extracted and reviewed. Cross-linking of individuals to population-based registries allowed retrieval of data on obstetrical and reproductive outcomes after FSS. Disease-free survival (DFS) and overall survival (OS) rates were compared (Kaplan-Meier method) between women who underwent FSS vs. radical surgery (RS).

Results

In total 83 women were identified; 36 who had FSS performed and 47 RS. The 5-year OS rate was 92% and no statistical differences between DFS or OS were found between women treated by FSS or RS. The recurrence rate after RS was 13% compared to 6% after FSS. Recurrences were more frequently found in women with stage IC tumor or with histologic subtypes with more aggressive behavior. In the FSS cohort, nine women gave birth to 12 healthy children, all delivered at fullterm. Only one women had received assisted reproductive technology treatment.

Conclusion

In this nationwide population-based cohort study natural fertility was maintained after FSS. Specific histologic subtypes showed greater prognostic impact on the oncological outcome than the use of FSS. Recurrences occurred after FSS, but none in the uterus, which questions the need of hysterectomy in young women with EOC.

Trial registration

This article reports the results of a healthcare intervention using the data prospectively registered in the Swedish population-based registries including the Quality Register for Gynecological Cancer, the National Death Register, the Swedish Medical Birth Register, and the National Quality Register for Assisted Reproduction.

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Discovering the molecular differences between right- and left-sided colon cancer using machine learning methods

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Abstract

Background

In recent years, the differences between left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have received increasing attention due to the clinicopathological variation between them. However, some of these differences have remained unclear and conflicting results have been reported.

Methods

From The Cancer Genome Atlas (TCGA), we obtained RNA sequencing data and gene mutation data on 323 and 283 colon cancer patients, respectively. Differential analysis was firstly done on gene expression data and mutation data between LCC and RCC, separately. Machine learning (ML) methods were then used to select key genes or mutations as features to construct models to classify LCC and RCC patients. Finally, we conducted correlation analysis to identify the correlations between differentially expressed genes (DEGs) and mutations using logistic regression (LR) models.

Results

We found distinct gene mutation and expression patterns between LCC and RCC patients and further selected the 30 most important mutations and 17 most important gene expression features using ML methods. The classification models created using these features classified LCC and RCC patients with high accuracy (areas under the curve (AUC) of 0.8 and 0.96 for mutation and gene expression data, respectively). The expression of PRAC1 and BRAF V600E mutation (rs113488022) were the most important feature for each model. Correlations of mutations and gene expression data were also identified using LR models. Among them, rs113488022 was found to have significance relevance to the expression of four genes, and thus should be focused on in further study.

Conclusions

On the basis of ML methods, we found some key molecular differences between LCC and RCC, which could differentiate these two groups of patients with high accuracy. These differences might be key factors behind the variation in clinical features between LCC and RCC and thus help to improve treatment, such as determining the appropriate therapy for patients.

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Disseminated intraosseous Kaposi’s sarcoma: A rare manifestation of HIV/AIDS

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Summary

Kaposi Sarcoma (KS), a mucocutaneous cancer that most frequently occurs in the context of Acquired Immunodeficiency Syndrome (AIDS) secondary to Human Immunodeficiency Virus (HIV), is a relatively benign condition, acting more as a marker of immunodeficiency than directly causing harm itself. However, it has been known to spread both locally and in a metastatic fashion, with reports of KS affecting almost all organ systems. One of the most rarely reported areas of involvement is the musculoskeletal system, with secondary osseous spread representing an even smaller subset of these. We report a case of biopsy proven disseminated intraosseous KS involving the entire imaged skeleton that occurred with HIV/AIDS, despite maximal treatment and normal imaging 8 months prior.

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The Combined Use of SBRT and Immunotherapy—a Literature Review

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Abstract

Purpose of Review

The purpose of this paper is to review all recent and relevant data regarding the combined use of immunotherapy (particularly immune checkpoint inhibitors) and radiotherapy.

Recent Findings

The use of radiotherapy, specifically stereotactic body radiation therapy (SBRT), and immunotherapy may be synergistic in the treatment of non-small cell lung cancer (NSCLC). There have been many preclinical and clinical studies that have shown that the combination of SBRT and immunotherapy is both safe and effective. In many cases, the benefits are greater than either SBRT or immunotherapy alone. Several ongoing trials are testing the combination of SBRT and immunotherapy for the treatment of all stages of NSCLC.

Conclusion

The combined use of SBRT and immunotherapy is a promising new development. The techniques may synergistically work better than either alone.

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Combined Inhibition of EGFR and VEGF Pathways in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

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Abstract

Purpose of Review

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The purpose of this systematic review and meta-analysis was to compare the efficacy of an EGFR tyrosine kinase inhibitor (TKI) plus a VEGF inhibitor with EGFR TKI alone for the treatment of EGFR-mutated NSCLC.

Recent Findings

We systematically searched for randomized controlled trials (RCT) that involved patients with EGFR-mutated metastatic NSCLC treated with combination therapy versus EGFR TKI alone. In a pooled analysis of 5 studies, treatment with the combination therapy was associated with statistically significant improvements in progression-free survival (hazard ratio [HR] 0.63, 95% CI [0.54, 0.75]) when compared with control. However, pooled data from 4 studies revealed no statistically significant differences between the 2 groups for overall survival (HR 1.00, 95% CI [0.68, 1.52]) and the objective response rate (relative risk [RR] 1.05, 95% CI [0.97, 1.14]).

Summary

In patients with metastatic EGFR-mutated NSCLC, treatment with EGFR TKI plus VEGF inhibition provided significant improvements in progression-free survival, but not in overall survival or objective response rate, when compared with treatment with EGFR TKI alone.

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How Should We Approach Locally Advanced Squamous Cell Carcinoma of Head and Neck Cancer Patients Ineligible for Standard Non-surgical Treatment?

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Abstract

Purpose of Review

Cisplatin has been established as one of the most important agents in multidisciplinary treatment for head and neck cancer (HNC). However, since HNC patients are often elderly and typically have several comorbidities, a limited number of patients can tolerate high-dose cisplatin in real-world HNC populations. We will provide a review of therapeutic alternatives to high-dose cisplatin-based treatment in the setting of definitive and postoperative chemoradiotherapy (CRT) or induction chemotherapy.

Recent Findings

Clinical criteria for CDDP ineligibility have been discussed in HNC. When considering cisplatin-based chemotherapy as part of a non-surgical approach, precise evaluation of the patient's physical condition, nutritional status, and comorbidities is needed. Upfront surgery is an important option with high curability, if a de-intensified non-surgical approach is estimated to be unavoidable. Although no prospective data are available regarding alternatives to definitive cisplatin-based combination therapy for patients undergoing a non-surgical approach, cetuximab, carboplatin, or split-dose cisplatin-based regimens may be employed for cisplatin-ineligible patients in clinical practice. The combination of immune checkpoint inhibitors with radiotherapy may be a promising novel approach, and some trials are currently targeting the specific cohort of patients ineligible for high-dose cisplatin.

Summary

There are no standard treatments for patients ineligible for high-dose cisplatin. A personalized treatment strategy should be proposed based on the individual benefit-to-risk ratio of each treatment option in patients ineligible for the standard of care. Prospective clinical trials for cisplatin-ineligible patients with locally advanced HNC still need to be performed

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Isocitrate Dehydrogenase, Patient-Reported Outcomes, and Cognitive Functioning of Glioma Patients: a Systematic Review

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Abstract

Purpose of Review

Isocitrate dehydrogenase (IDH) mutation status has important prognostic implications in glioma patients, with IDH wild-type (IDH-WT) gliomas being associated with worse prognosis and shorter survival when compared with IDH mutant (IDH-mut) gliomas. Optimization of quality of life is a priority in the management of glioma patients. The goal of this systematic review was to identify studies that explored the association of IDH mutation status with patient-reported outcomes (PROs) and cognitive functioning of glioma patients.

Recent Findings

Studies that evaluated the association of IDH mutation status with PROs and/or cognitive functioning of glioma patients were identified from the Pubmed/MEDLINE, Clarivate analytics, and Google Scholar databases. Eight studies (7 journal articles and 2 conference abstracts) with a total of 658 low-grade glioma and high-grade glioma patients investigated the association of cognitive functioning and/or QoL with IDH status. IDH-WT status was associated with greater cognitive impairment relative to IDH-Mut status in three studies, while one study did not find the association between IDH status and perioperative cognitive functioning. One study reported worse postoperative cognitive functioning patients with IDH-WT vs. IDH-mut gliomas. In one study, IDH-WT status was linked to greater impairment on physical and communication functioning after surgery.

Summary

IDH-WT gliomas are associated with greater cognitive burden than IDH-Mut tumors. The association of IDH status with QoL remains less clear. Assessment of IDH status should be considered when evaluating QoL and cognitive complaints of glioma patients. Further studies linking glioma molecular phenotypes with PROs and cognitive functioning are encouraged.

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The Value of Virtual Chromoendoscopy in the Workup of Patients with Head and Neck Squamous Cell Carcinoma

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Abstract

Purpose of Review

Second primary tumors (SPTs) significantly increase the mortality in patients with head and neck squamous cell carcinomas (HNSCCs). Virtual chromoendoscopy (VCE) could complement or replace lugol chromoendoscopy (LCE) for early esophageal second primary tumor (ESPT) detection. An overview of the existing techniques and their diagnostic performance in early detection of esophageal squamous cell neoplasms is provided.

Recent Findings

Nowadays, LCE is the golden standard to detect ESPTs. Recently, multiple new VCE techniques have been developed. Especially narrow-band imaging (NBI) is promising. It shows similar sensitivity to LCE, but a significantly higher specificity.

Summary

Patients with HNSCC are prone to develop ESPTs, both synchronous and metachronous, with a substantial negative impact on survival rates. Therefore, active screening and follow-up is necessary. LCE is an effective screening method, but has some disadvantages. Countering these drawbacks, NBI shows a high potential in early ESPT detection in high-risk patients. Additional multicenter studies are needed to compare diagnostic performance and cost-effectiveness of NBI and other VCE techniques with LCE.

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