Following Chemotherapy: Serum Cytokine (Tumor Necrosis Factor, Interleukin-2, Interleukin-11), Immunoglobulin, Complement, Vascular Endothelial Growth Factor Levels, and the Systemic Symptoms like Capillary Leak Syndrome

Several problems such as myalgia, arthralgia, fever, dyspnea, generalized edema, and pleural effusion can occur in cancer patients following the chemotherapy, especially at the first cycle of the first chemotherapy treatment. Although it is assumed that some cytokines are associated with the development of these symptoms and signs, their pathophysiology has not been discovered completely yet. They are usually mild, but they may rarely progress to the severe stage of “Systemic Capillary Leak Syndrome” with a high mortality rate. The objective of this study was to investigate the association between the serum levels of interleukin-2 (IL-2), interleukin-11 (IL-11), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and these symptoms and signs. A total of 44 cancer patients who had neither heart, lung, liver, renal, or thyroid disease were recruited into this study. Their symptoms and signs were examined and questioned before the first cycle of the first chemotherapy treatment and the 24 h after this chemotherapy. All participant’s serum samples were taken, and the VEGF, TNF, IL-2, and IL-11 levels were studied. There was no association between the chemotherapeutic drugs, and the symptoms and signs such as edema, dyspnea, coughing, and flu-like symptoms. There was a significant decrease in IL-11 levels in the other treatment group compared with the group receiving paclitaxel, docetaxel, gemcitabine, and vinorelbine in the first day following chemotherapy ( P = .006). However, no relation was observed between the symptoms and signs, the response to the chemotherapy, and the serum levels of VEGF, TNF, IL-2, and IL-11. These symptoms and life-threatening syndrome have been a current topic between the clinicians. Although some drugs and mediators are accused, its pathophysiology has not been discovered completely yet. In this study, we could not detect any association between the symptoms, signs, and the cytokine levels following the chemotherapy.

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry

Background: Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted ‘gold standards’ of tumour biology such as immunohistochemical measures is not established. Methods: A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation. Results: Hypoxia-inducible factor-1α was correlated with first-order kurtosis ( r = −0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness ( r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis ( r = −0.52, P = .047), fractal dimension ( r = 0.613, P = .015), and lacunarity ( r = −0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity ( r = 0.547, P = .035). Conclusions: The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.

Chemotherapy Resistance in Advanced Ovarian Cancer Patients

Ovarian cancer is the seventh most common gynaecologic malignancy seen in women. Majority of the patients with ovarian cancer are diagnosed at the advanced stage making prognosis poor. The standard management of advanced ovarian cancer includes tumour debulking surgery followed by chemotherapy. Various types of chemotherapeutic regimens have been used to treat advanced ovarian cancer, but the most promising and the currently used standard first-line treatment is carboplatin and paclitaxel. Despite improved clinical response and survival to this combination of chemotherapy, numerous patients either undergo relapse or succumb to the disease as a result of chemotherapy resistance. To understand this phenomenon at a cellular level, various macromolecules such as DNA, messenger RNA and proteins have been developed as biomarkers for chemotherapy response. This review comprehensively summarizes the problem that pertains to chemotherapy resistance in advanced ovarian cancer and provides a good overview of the various biomarkers that have been developed in this field.

Behavioural Response Alteration in Caenorhabditis elegans to Urine After Surgical Removal of Cancer: Nematode-NOSE (N-NOSE) for Postoperative Evaluation

The technique used for cancer monitoring is essential for effective cancer therapy. Currently, several methods such as diagnostic imaging and biochemical markers have been used for cancer monitoring, but these are invasive and show low sensitivity. A previous study reported that Caenorhabditis elegans sensitively discriminated patients with cancer from healthy subjects, based on the smell of a urine sample. However, whether C. elegans olfaction can detect the removal of cancerous tumours remains unknown. This study was conducted to examine C. elegans olfactory behaviour to urine samples collected from 78 patients before and after surgery. The diagnostic ability of the technique termed Nematode-NOSE (N-NOSE) was evaluated by receiver operating characteristic (ROC) analysis. The ROC curve of N-NOSE was higher than those of classic tumour markers. Furthermore, we examined the change in C. elegans olfactory behaviour following exposure to preoperative and postoperative samples. The results suggest that a reduction in attraction indicates the removal of the cancerous tumour. This study may lead to the development of a noninvasive and highly sensitive tool for evaluating postoperative cancer patients.

Multivariate Index Assay Is Superior to CA125 and HE4 Testing in Detection of Ovarian Malignancy in African-American Women

Objective: To review and analyze the serum values of risk of ovarian malignancy algorithm (ROMA) and multivariate index assay (MIA) in subgroups of women who underwent surgery for adnexal masses to determine sensitivity, specificity, and positive and negative predictive values for the detection of malignancy in different ethnic populations. Methods: Serum samples from 2 prospective trials of 1029 women in which 274 women diagnosed with malignancy were analyzed for ROMA scores and MIA results. Biomarker data were obtained from the previous prospective studies that validated the MIA test. Of these, 250 women were Caucasian (C) and 24 were African-American (AA). Sensitivity, specificity, positive and negative predictive values, and confidence intervals for preoperative test results were calculated using DTComPair package of the R programming language. In premenopausal women, a ROMA value equal to or greater than 1.14 indicates a high risk of finding epithelial ovarian cancer. In premenopausal women, MIA values greater than 5.0 are associated with a greater risk of malignancy. In postmenopausal women, a ROMA value equal to or greater than 2.99 indicates a high risk of finding epithelial ovarian cancer. In postmenopausal women, MIA values greater than 4.4 are associated with a greater risk of malignancy. Results: Primary ovarian malignancy was diagnosed in 179 cases (167 C/12 AA) and metastatic disease to the ovary in an additional 27 cases (22 C/5 AA). Overall results are shown below. Conclusions: Our results demonstrate that ROMA in AA women with adnexal masses have lower sensitivity for the detection of malignancy than does MIA. Implementation of MIA in the evaluation of adnexal masses will increase the sensitivity of the detection of malignancy compared with ROMA, with the most marked results in AA women.

Detection of Micro-invasion in Sudanese Oral Verrucous Carcinoma Samples Using Syndecan-1 Stain

Aim: Verrucous carcinoma (VC) is a low-grade rare variant of squamous cell carcinoma (SCC). Syndecan-1 (CD138) is a heparan sulfate proteoglycan which participates in cell-to-cell adhesion and cell-matrix interaction. Being misled by the apparent non-aggressive nature of VC, some clinicians and pathologists believe that this tumor is not an aggressive tumor, not realizing the fact that some of these lesions may contain nests or foci of well-differentiated SCC. This study aimed to assess syndecan-1 expression of VC and detection of micro-invasion in VC using syndecan-1 immunohistochemical (IHC) stain. Methods: Observational analytical study of 34 paraffin block of VC cases and 24 cases of variable grades of oral epithelial dysplasia. Cases were stained by hematoxylin and eosin (H&E) and then IHC stain for syndecan-1 was applied. Nine paraffin blocks from specimens of normal oral mucosa were used as the reference group for syndecan-1 stain positivity. Results: In this study, we found that 32 (94.1%) out of 34 of verrucous carcinoma cases showed loss of syndecan-1 expression. Moreover, highly statistically significant association was found between the presence of suggestive micro-invasion in H&E and loss of syndecan-1 expression in micro-invasive area in the same case. Conclusions: In conclusion, syndecan-1 stain can be used as a biomarker in detection of micro-invasion in verrucous carcinoma.

Systematic Review: Genetic Associations for Prognostic Factors of Urinary Bladder Cancer

Introduction: Many germline associations have been reported for urinary bladder cancer (UBC) outcomes and prognostic characteristics. It is unclear whether there are overlapping genetic patterns for various prognostic endpoints. We aimed to review contemporary literature on genetic associations with UBC prognostic outcomes and to identify potential overlap in reported genes. Methods: EMBASE, MEDLINE, and PubMed databases were queried for relevant articles in English language without date restrictions. The initial search identified 1346 articles. After exclusions, 112 studies have been summarized. Cumulatively, 316 single-nucleotide polymorphisms (SNPs) were reported across prognostic outcomes (recurrence, progression, death) and characteristics (tumor stage, grade, size, age, risk group). There were considerable differences between studied outcomes in the context of genetic associations. The most commonly reported SNPs were located in OGG1, TP53, and MDM2. For outcomes with the highest number of reported associations (ie, recurrence and death), functional enrichment annotation yields different terms, potentially indicating separate biological mechanisms. Conclusions: Our study suggests that all UBC prognostic outcomes may have different biological origins with limited overlap. Further validation of these observations is essential to target a phenotype that could best predict patient outcome and advance current management practices.

RBBP6 Is Abundantly Expressed in Human Cervical Carcinoma and May Be Implicated in Its Malignant Progression

RBBP6 is a novel gene encoding splicing-associated proteins. There are 3 protein isoforms (isoforms 1-3). RBBP6 isoforms 1 has been shown to interact with both p53 and Rb. It also plays a role in the induction of apoptosis and the regulation of the cell cycle. The expression of RBBP6 has been documented in several cancers but RBBP6 expression in cervical cancer has not been well studied. The aim of this study was to establish expression levels and tissue distribution of the RBBP6 gene products at both protein and messenger RNA (mRNA) levels in cervical cancer by immunocytochemistry and in situ hybridization (ISH). A link between RBBP6 expression, apoptosis, and cervical cancer progression was also investigated. RBBP6 mRNA was expressed in the nuclei and cytoplasm of normal and tumour cervical epithelium. In general, expression was high in the cytoplasm and nuclei of moderately differentiated and invasive carcinoma. Immunolabelling results were confirmed by image analysis and ISH experiments. Apoptosis assays using TUNEL correlated with the expression of the RBBP6 gene in all examined cases. This is the first report on the abundant expression of RBBP6 in cervical cancer and its involvement in the malignant progression of cervical cancer. Because of the high expression and corresponding pro-apoptotic activity observed in cervical cancer cells in this study, we suggest that RBBP6 is involved in the malignant progression of cervical cancer. RBBP6 proteins can therefore be targeted for therapeutic interventions against cervical cancer.

Urine Biomarkers for the Early Detection of Ovarian Cancer – Are We There Yet?

Ovarian cancer affects around 7500 women in the United Kingdom every year. Despite this, there is no effective screening strategy or standard treatment for ovarian cancer. If diagnosed during stage I, ovarian cancer has a 90% 5-year survival rate; however, there is usually a masking of symptoms which leads to an often late-stage diagnosis and correspondingly poor survival rate. Current diagnostic methods are invasive and consist of a pelvic examination, transvaginal ultrasonography, and blood tests to detect cancer antigen 125 (CA125). Unfortunately, surgery is often still required to make a positive diagnosis. To address the need for accurate, specific, and non-invasive diagnostic methods, there has been an increased interest in biomarkers identified through non-invasive tests as tools for the earlier diagnosis of ovarian cancer. Although most studies have focused on the identification of biomarkers in blood, the ease of availability of urine and the high patient compliance rates suggest that it could provide a promising resource for the screening of patients for ovarian cancer.

Integrating Circulating Immunological and Sputum Biomarkers for the Early Detection of Lung Cancer

We have demonstrated that assessments of microRNA (miRNA) expressions in circulating peripheral blood mononucleated cell (PBMC) and sputum specimens, respectively, may help diagnose lung cancer. To assess the individual and combined analysis of the miRNAs across the different body fluids for lung cancer early detection, we analyse a panel of 3 sputum miRNAs (miRs-21, 31, and 210) and a panel of 2 PBMC miRNAs (miRs-19b-3p and 29b-3p) in a discovery cohort of 68 patients with lung cancer and 66 cancer-free smokers. We find that integrating 2 sputum miRNAs (miRs-31 and 210) and 1 PBMC miRNA (miR-19b-3p) has higher sensitivity (86.8%) and specificity (92.4%) compared with the individual panels. The synergistic value of the integrated panel of 3 biomarkers is confirmed in a validation cohort, independent of stage and histological type of lung cancer, and patients’ age, sex, and ethnicity. Integrating circulating immunological and sputum biomarkers could improve the early detection of lung cancer.