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South Africa

Cancer Statistics
Population in 2012: 50.7m
People newly diagnosed with cancer (excluding NMSC) / yr: 77,400
Age-standardised rate, incidence per 100,000 people/yr: 187.1
Risk of getting cancer before age 75:19.0%
People dying from cancer /yr: 47,400
Data from IARC GlobalCan (2012)
Regional Organisations
Latest Research Publications from South Africa

Regional Organisations (19 links)

Latest Research Publications from South Africa

Soyele OO, Effiom OA, Lawal AO, et al.
A multi-centre evaluation of malignant odontogenic tumours in Nigeria.
Pan Afr Med J. 2019; 33:18 [PubMed] Free Access to Full Article Related Publications
Introduction: odontogenic tumors originate from neoplastic transformation of the remnants of tooth forming apparatus. There are varying degrees of inductive interactions between odontogenic ectomesenchyme and epithelium during odontogenesis, leading to lesions that vary from benign to malignant. Malignant odontogenic tumours (MOTs) are very rare and are classified according to embryonic tissue of origin. Recently, there has been a few changes to the classification of MOTs according to the World Health Organization's (WHO) classification in 2017. This study aims to evaluate and reclassify MOTs, using a multi-centre approach in some major tertiary dental hospitals in Nigeria.
Methods: this study reviewed the clinicopathological data on 63 cases of MOT diagnosed over 25 years in five major tertiary dental hospitals in Nigeria. All MOT cases were reclassified according to the recent revision to the 2017 WHO classification of odontogenic tumours.
Results: from a total of 10,446 biopsies of oral and jaw lesions seen at the 5 study centres over the 25-year study period, 2199 (21.05%) cases were found to be odontogenic tumours (OTs), of which 63 were MOT. MOTs constituted 0.60% of the total biopsy cases and 2.86% of OTs. Odontogenic carcinomas presented with a mean age higher than odontogenic sarcomas. According to our 2017 WHO reclassification of MOTs, odontogenic carcinomas, ameloblastic carcinomas and primary intraosseous carcinomas were found to be the top three lesions, respectively. Carcinosarcomas were found to be extremely rare.
Conclusion: using a multi-centre approach is a robust way to reduce diagnostic challenges associated with rare maxillofacial lesions such as MOTs.

Nkfusai NC, Mubah TM, Yankam BM, et al.
Prevalence of precancerous cervical lesions in women attending Mezam Polyclinic Bamenda, Cameroon.
Pan Afr Med J. 2019; 32:174 [PubMed] Free Access to Full Article Related Publications
Introduction: Precancerous cervical lesion is significantly a health problem globally. Thus, screening targeting women between the ages of 17-60 is being undertaken in developing countries, including Cameroon. Over 50% (7.8 per 100,000) women die of cervical cancer every year. This study was to determine the prevalence of precancerous cervical lesion, the age demography and access the risk factor.
Methods: A hospital-based cross-sectional study was conducted from August 09th to October 17th 2017. A total of 60 women participated, and were screened for precancerous cervical lesion. Data were collected by using a questionnaire. Visual inspection with acetic acid and visual inspection with Lugol's iodine was applied for the screening. SPSS version 16.0 was used for data entry and analysis. Logistic regression analysis was fitted and odds ratios with 95% confidence intervals and p-values were computed to identify factors associated with precancerous cervical cancer lesion.
Results: Out of 60 study participants, 2(3.33%) were found to be positive for precancerous cervical cancer lesion.
Conclusion: The prevalence of precancerous cervical lesion in women that consulted at the Mezam polyclinic is high.

Nkfusai NC, Cumber SN, Williams T, et al.
Cervical cancer in the Bamenda Regional Hospital, North West Region of Cameroon: a retrospective study.
Pan Afr Med J. 2019; 32:90 [PubMed] Free Access to Full Article Related Publications
Introduction: Cervical cancer is ranked the 7
Methods: The objective of this study was to determine the proportion of cervical cancer among other types of cancers in the cancer registry of the Bamenda Regional Hospital, North West Region of Cameroon from past records. We reviewed all records from the registry of patients who attended the Bamenda Regional Hospital to screen and/or be operated upon for cervical cancer and other types of cancer. Socio-demographic and clinical characteristics of cases were captured using a data collection sheet: age, type of cancer, stage of cancer, type of surgery carried out and date of surgery. Data were entered and analysed in Statistical Package for Social Sciences (SPSS) version 25 software.
Results: 59 cancer cases were received in the center between 2012 and 2017. Of these, 31 (52%) had cervical cancer. Most patients who screened positive for cancer of the cervix were of the 50-54 age groups. Most of these patients (47.5%), were received at late stages (stages 3 and 4).
Conclusion: Over half (52%) of the patients receiving cancer care in this center have cervical cancer and generally turn up late for management.

Michelow P, Field AS
Spindle Cell Lesions of the Breast on Fine-Needle Aspiration Biopsy: A Miscellany of Masses.
Acta Cytol. 2019; 63(4):328-339 [PubMed] Related Publications
A variety of primary breast and metastatic lesions to the breast can present with spindle cell cytomorphology. These lesions may range from benign reactive or inflammatory lesions to high-grade malignancies. Spindle cell lesions of the breast are not often seen on fine-needle aspiration biopsy (FNAB) but need to be correctly managed when they are encountered. While mesenchymal lesions of the breast have a spindle morphology, lesions derived from the epithelium and myoepithelium can be spindled as well. By assessing if the lesion comprises spindle cells only or if other components such as epithelial cells are apparent and then determining whether the spindle cells appear bland or pleomorphic, together with close clinicoradiologic correlation and prudent use of ancillary tests, a variety of lesions can be diagnosed on FNAB. However, core needle biopsy or excision biopsy may be required in some patients. The cytomorphology, ancillary studies, and clinicoradiologic findings of a range of spindle cell lesions of the breast are further discussed.

Field AS, Raymond WA, Rickard M, et al.
The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology.
Acta Cytol. 2019; 63(4):257-273 [PubMed] Related Publications
The International Academy of Cytology (IAC) gathered together a group of cytopathologists expert in breast cytology who, working with clinicians expert in breast diagnostics and management, have developed the IAC Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy (FNAB) Cytology. The project was initiated with the first cytopathology group meeting in Yokohama at the 2016 International Congress of Cytology. This IAC Yokohama System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy (ROM) and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category will be presented more fully in a subsequent atlas. The System emphasizes that the crucial requirements for diagnostic breast FNAB cytology are a high standard for the performance of the FNAB and for the making of direct smears, and well-trained experienced cytopathologists to interpret the material. The performance indicators of breast FNAB, including specificity and sensitivity, negative predictive value, positive predictive value and ROM stated in this article have been derived from the recent literature. The current practice of breast FNAB has evolved with the increasing use of ultrasound guidance and rapid on-site evaluation. Two recent publications have shown a range of ROM for the insufficient/inadequate category of 2.6-4.8%, benign 1.4-2.3%, atypical 13-15.7%, suspicious of malignancy 84.6-97.1%, and malignant 99.0-100%. The management algorithm in the System provides options because there are variations in the management of breast lesions using FNAB and core-needle biopsy in those countries utilizing the "triple test" of clinical, imaging, and FNAB assessment, and also variations in the availability of CNB and imaging in low- and middle-income countries. The System will stimulate further discussion and research, particularly in the cytological diagnostic features of specific lesions within each category and in management recommendations. This will lead to continuing improvements in the care of patients with breast lesions and possible modifications to the IAC Yokohama System.

Antel K, Levetan C, Mohamed Z, et al.
The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting.
BMC Cancer. 2019; 19(1):384 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV.
METHODS: We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay.
RESULTS: Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival.
CONCLUSIONS: Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.

Mapekula L, Ramorola BR, Goolam Hoosen T, Mowla S
The interplay between viruses & host microRNAs in cancer - An emerging role for HIV in oncogenesis.
Crit Rev Oncol Hematol. 2019; 137:108-114 [PubMed] Related Publications
Human cancers attributed to viral infections represent a growing proportion of the global cancer burden, with these types of cancers being the leading cause of morbidity and mortality in some regions. The concept that viruses play a causal role in human cancers is not new, but the mechanism thereof, while well described for some viruses, still remains elusive and complex for others, especially in the case of HIV-associated B-cell derived cancers. In the last decade, compelling evidence has demonstrated that cellular microRNAs are deregulated in cancers, with an increasing number of studies identifying microRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools. Recent research demonstrates that viruses and viral components manipulate host microRNA expressions to their advantage, and the emerging picture suggests that the virus/microRNA pathway interaction is defined by a plethora of complex mechanisms. In this review, we highlight the current knowledge on virus/microRNA pathway interactions in the context of cancer and provide new insights on HIV as an oncogenic virus.

Tapera O, Kadzatsa W, Nyakabau AM, et al.
Sociodemographic inequities in cervical cancer screening, treatment and care amongst women aged at least 25 years: evidence from surveys in Harare, Zimbabwe.
BMC Public Health. 2019; 19(1):428 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cervical cancer is the most commonly diagnosed cancer among women in Zimbabwe; however; access to screening and treatment services remain challenged. The objective of this study was to investigate socio-demographic inequities in cervical cancer screening and utilization of treatment among women in Harare, Zimbabwe.
METHODS: Two cross sectional surveys were conducted in Harare with a total sample of 277 women aged at least 25 years. In the community survey, stratified random sampling was conducted to select 143 healthy women in Glen View, Cranborne, Highlands and Hopely communities of Harare to present high, medium, low density suburbs and rural areas respectively. In the patient survey, 134 histologically confirmed cervical cancer patients were also randomly selected at Harare hospital, Parirenyatwa Hospital and Island Hospice during their routine visits or while in hospital admission. All consenting participants were interviewed using a validated structured questionnaire programmed in Surveytogo software in an android tablet. Data was analyzed using STATA version 14 to yield descriptive statistics, bivariate and multivariate logistic regression outcomes for the study.
RESULTS: Women who reported ever screening for cervical cancer were only 29%. Cervical cancer screening was less likely in women affiliated to major religions (p < 0.05) and those who never visited health facilities or doctors or visited once in previous 6 months (p < 0.05). Ninety-two (69%) of selected patients were on treatment. Women with cervical cancer affiliated to protestant churches were 68 times [95% CI: 1.22 to 381] more likely to utilize treatment and care services compared to those in other religions (p = 0.040). Province of residence, education, occupation, marital status, income (personal and household), wealth, medical aid status, having a regular doctor, frequency of visiting health facilities, sources of cervical cancer information and knowledge of treatability of cervical cancer were not associated with cervical cancer screening and treatment respectively.
CONCLUSION: This study revealed few variations in the participation of women in cervical cancer screening and treatment explained only by religious affiliations and usage of health facilities. Strengthening of health education in communities including churches and universal healthcare coverage are recommended strategies to improve uptake of screening and treatment of cervical cancer.

Ferreira MA, Gamazon ER, Al-Ejeh F, et al.
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
Nat Commun. 2019; 10(1):1741 [PubMed] Free Access to Full Article Related Publications
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Crous A, Dhilip Kumar SS, Abrahamse H
Effect of dose responses of hydrophilic aluminium (III) phthalocyanine chloride tetrasulphonate based photosensitizer on lung cancer cells.
J Photochem Photobiol B. 2019; 194:96-106 [PubMed] Related Publications
Photodynamic therapy (PDT) is a promising approach for the treatment of different types of cancer and has been brought into focus for its synergy, compatibility, repeatability, relatively inexpensive cost and it's typically more efficacious nature. Photosensitizers (PSs) play a major role in PDT and are the core of this specific therapy. Al (III) Phthalocyanine Chloride Tetra sulfonic Acid (AlPcS

Fagan JJ, Chaturvedi P, Kowalski LP
Treatment Options for Hypopharyngeal Cancer in Developing Countries in Africa/South America/Asia.
Adv Otorhinolaryngol. 2019; 83:159-166 [PubMed] Related Publications
Most cancers occur in developing countries, and therefore, a discussion about cancer care would be incomplete without providing a developing world perspective. This chapter focuses on challenges and practices relating to hypopharyngeal cancer in limited-resource public healthcare systems in developing countries and specifically in Sub-Saharan Africa, India and South America and by extension, most patients in the developing world. Management of hypopharyngeal cancer must be adapted to the availability of specialised diagnostic and therapeutic services, radiotherapy and surgical expertise, and tailored to patient factors such as reliability of follow-up and social support. A particular challenge for physicians is to decide who can be denied the opportunity to be cured when the burden of cancer cases exceeds available resources. Public education campaigns about reducing risk factors for hypopharyngeal cancer are an important aspect of reducing the burden of cancer.

Heyer EE, Deveson IW, Wooi D, et al.
Diagnosis of fusion genes using targeted RNA sequencing.
Nat Commun. 2019; 10(1):1388 [PubMed] Free Access to Full Article Related Publications
Fusion genes are a major cause of cancer. Their rapid and accurate diagnosis can inform clinical action, but current molecular diagnostic assays are restricted in resolution and throughput. Here, we show that targeted RNA sequencing (RNAseq) can overcome these limitations. First, we establish that fusion gene detection with targeted RNAseq is both sensitive and quantitative by optimising laboratory and bioinformatic variables using spike-in standards and cell lines. Next, we analyse a clinical patient cohort and improve the overall fusion gene diagnostic rate from 63% with conventional approaches to 76% with targeted RNAseq while demonstrating high concordance for patient samples with previous diagnoses. Finally, we show that targeted RNAseq offers additional advantages by simultaneously measuring gene expression levels and profiling the immune-receptor repertoire. We anticipate that targeted RNAseq will improve clinical fusion gene detection, and its increasing use will provide a deeper understanding of fusion gene biology.

Gwangwa MV, Joubert AM, Visagie MH
Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines.
Biol Res. 2019; 52(1):15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tumourigenic cells modify metabolic pathways in order to facilitate increased proliferation and cell survival resulting in glucose- and glutamine addiction. Previous research indicated that glutamine deprivation resulted in potential differential activity targeting tumourigenic cells more prominently. This is ascribed to tumourigenic cells utilising increased glutamine quantities for enhanced glycolysis- and glutaminolysis. In this study, the effects exerted by glutamine deprivation on reactive oxygen species (ROS) production, mitochondrial membrane potential, cell proliferation and cell death in breast tumourigenic cell lines (MCF-7, MDA-MB-231, BT-20) and a non-tumourigenic breast cell line (MCF-10A) were investigated.
RESULTS: Spectrophotometry demonstrated that glutamine deprivation resulted in decreased cell growth in a time-dependent manner. MCF-7 cell growth was decreased to 61% after 96 h of glutamine deprivation; MDA-MB-231 cell growth was decreased to 78% cell growth after 96 h of glutamine deprivation, MCF-10A cell growth was decreased 89% after 96 h of glutamine deprivation and BT-20 cell growth decreased to 86% after 24 h of glutamine deprivation and remained unchanged until 96 h of glutamine deprivation. Glutamine deprivation resulted in oxidative stress where superoxide levels were significantly elevated after 96 h in the MCF-7- and MDA-MB-231 cell lines. Time-dependent production of hydrogen peroxide was accompanied by aberrant mitochondrial membrane potential. The effects of ROS and mitochondrial membrane potential were more prominently observed in the MCF-7 cell line when compared to the MDA-MB-231-, MCF-10A- and BT-20 cell lines. Cell cycle progression revealed that glutamine deprivation resulted in a significant increase in the S-phase after 72 h of glutamine deprivation in the MCF-7 cell line. Apoptosis induction resulted in a decrease in viable cells in all cell lines following glutamine deprivation. In the MCF-7 cells, 87.61% of viable cells were present after 24 h of glutamine deprivation.
CONCLUSION: This study demonstrates that glutamine deprivation resulted in decreased cell proliferation, time-dependent- and cell line-dependent ROS generation, aberrant mitochondrial membrane potential and disrupted cell cycle progression. In addition, the estrogen receptor positive MCF-7 cell line was more prominently affected. This study contributes to knowledge regarding the sensitivity of breast cancer cells and non-tumorigenic cells to glutamine deprivation.

Kaschula CH, Tuveri R, Ngarande E, et al.
The garlic compound ajoene covalently binds vimentin, disrupts the vimentin network and exerts anti-metastatic activity in cancer cells.
BMC Cancer. 2019; 19(1):248 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Garlic has been used for centuries for its flavour and health promoting properties that include protection against cancer. The vinyl disulfide-sulfoxide ajoene is one of the phytochemicals found in crushed cloves, hypothesised to act by S-thiolating reactive cysteines in target proteins.
METHODS: Using our fluorescently labelled ajoene analogue called dansyl-ajoene, ajoene's protein targets in MDA-MB-231 breast cancer cells were tagged and separated by 2D electrophoresis. A predominant band was identified by MALDI-TOF MS/MS to be vimentin. Target validation experiments were performed using pure recombinant vimentin protein. Computational modelling of vimentin bound to ajoene was performed using Schrödinger and pK
RESULTS: The dominant protein tagged by dansyl-ajoene was identified to be the 57 kDa protein vimentin. The vimentin target was validated to reveal that ajoene and dansyl-ajoene covalently bind to recombinant vimentin via a disulfide linkage at Cys-328. Computational modelling showed Cys-328 to be exposed at the termini of the vimentin tetramer. Treatment of MDA-MB-231 or HeLa cells with a non-cytotoxic concentration of ajoene caused the vimentin filament network to condense; and to increase vimentin protein expression. Ajoene inhibited the invasion and migration of both cancer cell lines which was found to be dependent on the presence of vimentin. Vimentin overexpression caused cells to become more migratory, an effect that was completely rescued by ajoene.
CONCLUSIONS: The garlic-derived phytochemical ajoene targets and covalently modifies vimentin in cancer cells by S-thiolating Cys-328. This interaction results in the disruption of the vimentin filament network and contributes to the anti-metastatic activity of ajoene in cancer cells.

Zhang C, Mao M, Guo X, et al.
Nomogram based on homogeneous and heterogeneous associated factors for predicting bone metastases in patients with different histological types of lung cancer.
BMC Cancer. 2019; 19(1):238 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer.
PATIENTS AND METHODS: This study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan-Meier method and the survival differences were tested by the log-rank test.
RESULTS: A total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89-4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001).
CONCLUSION: Different lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.

Rapoport BL, Anderson R
Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy.
Int J Mol Sci. 2019; 20(4) [PubMed] Free Access to Full Article Related Publications
Immunogenic cell death (ICD), which is triggered by exposure of tumor cells to a limited range of anticancer drugs, radiotherapy, and photodynamic therapy, represents a recent innovation in the revitalized and burgeoning field of oncoimmunnotherapy. ICD results in the cellular redistribution and extracellular release of damage-associated molecular patterns (DAMPs), which have the potential to activate and restore tumor-targeted immune responses. Although a convincing body of evidence exists with respect to the antitumor efficacy of ICD in various experimental systems, especially murine models of experimental anticancer immunotherapy, evidence for the existence of ICD in the clinical setting is less compelling. Following overviews of hallmark developments, which have sparked the revival of interest in the field of oncoimmunotherapy, types of tumor cell death and the various DAMPs most prominently involved in the activation of antitumor immune responses, the remainder of this review is focused on strategies which may potentiate ICD in the clinical setting. These include identification of tumor- and host-related factors predictive of the efficacy of ICD, the clinical utility of combinatorial immunotherapeutic strategies, novel small molecule inducers of ICD, novel and repurposed small molecule immunostimulants, as well as the critical requirement for validated biomarkers in predicting the efficacy of ICD.

Feng Y, Ramnarine VR, Bell R, et al.
Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer.
BMC Genomics. 2019; 20(1):146 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since most precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing a causal relationship between microbial inflammation and PCa requires a comprehensive analysis of the prostate microbiome. The aim of this study was to characterize the microbiome in prostate tissue of PCa patients and investigate its association with tumour clinical characteristics as well as host expression profiles.
RESULTS: The metagenome and metatranscriptome of tumour and the adjacent benign tissues were assessed in 65 Chinese radical prostatectomy specimens. Escherichia, Propionibacterium, Acinetobacter and Pseudomonas were abundant in both metagenome and metatranscriptome, thus constituting the core of the prostate microbiome. The biodiversity of the microbiomes could not be differentiated between the matched tumour/benign specimens or between the tumour specimens of low and high Gleason Scores. The expression profile of ten Pseudomonas genes was strongly correlated with that of eight host small RNA genes; three of the RNA genes may negatively associate with metastasis. Few viruses could be identified from the prostate microbiomes.
CONCLUSIONS: This is the first study of the human prostate microbiome employing an integrated metagenomics and metatranscriptomics approach. In this Chinese cohort, both metagenome and metatranscriptome analyses showed a non-sterile microenvironment in the prostate of PCa patients, but we did not find links between the microbiome and local progression of PCa. However, the correlated expression of Pseudomonas genes and human small RNA genes may provide tantalizing preliminary evidence that Pseudomonas infection may impede metastasis.

Einstein MH, Ndlovu N, Lee J, et al.
Cisplatin and radiation therapy in HIV-positive women with locally advanced cervical cancer in sub-Saharan Africa: A phase II study of the AIDS malignancy consortium.
Gynecol Oncol. 2019; 153(1):20-25 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
PURPOSE: To determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART).
PATIENTS AND METHODS: Eligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.4-45 Gy external beam radiation therapy followed by high dose rate brachytherapy concomitant with up to six weekly doses of cisplatin 40 mg/m2 and were followed for 12 months.
RESULTS: Sixty-four women were screened at two sites in sub-Saharan Africa, of whom 40 eligible participants were enrolled, for a screening ratio of 1.60. Of the 38 eligible participants who initiated study treatment, 31 (82%) completed treatment. By the 12-month follow-up visit, 7 women had died of disease and 29 of 31 (94%) returned for follow-up. One-year progression-free survival was 76.3% (95% CI, 59.4-86.9%), and did not significantly differ according to stage at entry (p = 0.581). Participant-reported adherence to ART was high; by 12 months, 93% of participants had an undetectable viral load. The most common grade 3 or 4 adverse event was decreased lymphocyte count that affected all treated participants. Non-hematologic serious adverse events were similar to those observed in women with LACC without HIV infection.
CONCLUSIONS: The majority of HIV-infected women with LACC can complete concomitant chemoradiotherapy with the same cisplatin dose used in HIV-uninfected women with comparable tolerability and high ART adherence while on treatment.

Scott AJ, McGuire JK, Manning K, et al.
Quality of life after total laryngectomy: evaluating the effect of socioeconomic status.
J Laryngol Otol. 2019; 133(2):129-134 [PubMed] Related Publications
OBJECTIVE: Total laryngectomy is considered the primary treatment modality for advanced laryngeal carcinoma. This study assessed the quality of life in patients after total laryngectomy, and ascertained whether quality of life is affected by socioeconomic status.
METHOD: Forty-seven patients (20 state- and 27 private-sector) who underwent total laryngectomy between 1998 and 2014 responded to the University of Washington Quality of Life Questionnaire, the Voice-Related Quality of Life Questionnaire and the Brief Illness Perception Questionnaire.
RESULTS: Significant differences were found in socioeconomic status between state- and private-sector patients (p < 0.001). There was no significant difference in overall quality of life between groups (p = 0.210). State-sector patients scored significantly higher Voice-Related Quality of Life Questionnaire scores (p = 0.043). Perception of illness did not differ significantly between groups.
CONCLUSION: Overall quality of life after total laryngectomy appears to be similar in patients from different socioeconomic backgrounds. However, patients from lower socioeconomic circumstances have better voice-related quality of life. The results illustrate the importance of including socioeconomic status when reporting voice outcomes in total laryngectomy patients.

Matlou GG, Managa M, Nyokong T
Effect of symmetry and metal nanoparticles on the photophysicochemical and photodynamic therapy properties of cinnamic acid zinc phthalocyanine.
Spectrochim Acta A Mol Biomol Spectrosc. 2019; 214:49-57 [PubMed] Related Publications
In this study, a novel asymmetric cinnamic acid zinc phthalocyanine (ZnPc, 1) containing three tert-butyl substituents is reported. The asymmetric ZnPc (1) is further linked to amino functionalized magnetic nanoparticles (AMNPs) (1-AMNPs) and to cysteine functionalized silver nanoparticles (cys-AgNPs) (1-cys-AgNPs) through an amide bond. 1-AMNPs and 1-cys-AgNPs improved the triplet and singlet oxygen quantum yields of complex 1, this was also observed with the previously reported 2-AMNPs when compared to 2 while 3-AMNPs yielded an unexpected decrease in triplet quantum yield as compared to 3. The silver nanoparticles (1-cys-AgNPs) had a better effect on improving the singlet oxygen quantum yield of complex 1 than the magnetic nanoparticles (1-AMNPs). The Pcs and conjugates recorded low cell cytotoxicity in the dark and high photocytotoxicity against MCF-7 cells in-vitro. MCF-7 cell viabilities of less than 50% were recorded at 80 μg/mL making the Pcs and conjugates under study potential candidates for use as photosensitizers in cancer therapy.

Guo X, Xu Y, Wang X, et al.
Advanced Hepatocellular Carcinoma with Bone Metastases: Prevalence, Associated Factors, and Survival Estimation.
Med Sci Monit. 2019; 25:1105-1112 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
BACKGROUND The objective of the present research was to explore the prevalence, risk, and prognostic factors associated with bone metastases (BM) in newly diagnosed hepatocellular carcinoma (HCC) patients. MATERIAL AND METHODS From 36 507 HCC patients who were registered in Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 1263 with BM at the initial diagnosis of HCC from 2010 to 2014. Kaplan-Meier curves and log-rank tests were used to estimate overall survival for different subgroups. Univariate and multivariate logistic and Cox regression analyses were performed to identify risk factors and independent prognostic factors for BM. RESULTS A total of 1567 (4.29%) HCC patients were detected with BM at initial diagnosis. Male sex, unmarried status, higher T stage, lymph node involvement, intrahepatic metastases, and extrahepatic metastases (lung or brain) were positively associated with BM. The median survival of the patients was 3.00 months (95% CI: 2.77-3.24 months). Marital status and primary tumor surgery were independently associated with the better survival. CONCLUSIONS A list of factors associated with BM occurrence and the prognosis of the advanced HCC patients with BM were found. These associated factors may provide a reference for BM screening in HCC and guide prophylactic treatment in clinical settings.

Gabriel IO, Mayers PM
Effects of a psychosocial intervention on the quality of life of primary caregivers of women with breast cancer.
Eur J Oncol Nurs. 2019; 38:85-91 [PubMed] Related Publications
PURPOSE: Breast cancer is the leading form of cancer among women in Nigeria. The care of such patients has shifted from hospital-based care to home and community care, with the resultant increase in responsibility and burden on caregivers. The study aimed to implement and evaluate the effectiveness of a psychosocial intervention programme on the quality of life (QOL) and caregiver burden of the primary caregivers of women with breast cancer.
METHOD: This was a quasi-experimental study with 108 primary caregivers (54 in both intervention and control groups). The intervention comprised six 90-min educational sessions, held weekly. Topics included information about breast cancer, the emotional aspect of caring, adjustment to the role of caregiver and communication strategies. The intervention group received the psychosocial intervention programme in addition to routine care, and the control group received routine care. Primary outcome (caregiver burden) and caregiver QOL were measured using the Zarit Burden Interview (ZBI) and Caregiver Quality of Life Index-Cancer (CQOLC) at baseline, week six and week 12.
RESULTS: The psychosocial intervention reduced caregiver burden at both T1 and T2 (p = 0.000, p = 0.018 respectively) and improved the caregiver QOL (p = 0.000, p = 0.020 respectively) in the intervention group compared to the control group.
CONCLUSION: The psychosocial intervention programme had a positive effect on caregiver burden and QOL. Issues such as sustainability of such programmes and advocacy relating to caregiver burden need further research.

Cassiem W, de Kock M
The anti-proliferative effect of apricot and peach kernel extracts on human colon cancer cells in vitro.
BMC Complement Altern Med. 2019; 19(1):32 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
BACKGROUND: Colorectal malignant neoplasms is one of the leading causes of death in both men and women in the developed world and the incidence has recently increased markedly in South Africa. Studies have highlighted the beneficial effects of Amygdalin, a cyanogenic compound found in both peach and apricot kernels, in its ability to suppress the development of colon cancer. The focus of this study was to investigate the potential anti-proliferative properties of various apricot and peach kernels extractions from South Africa and China and to monitor alterations in cell cycle kinetics in colon cancer cells.
METHODS: Studies were conducted on HT-29 colon cancer cells. The interactive role of three different kernel extractions on the modulation of cell proliferation, apoptosis and cell cycle progression was monitored over 24, 48 and 72 h periods.
RESULTS: After 24 h, all extracts of the South African apricot kernels had a dose related bi-phasic proliferative effect on the HT-29 cells. It stimulated cell proliferation at the lowest and highest concentrations while at 500 μg/mL it inhibited cell proliferation. In contrast, after 72 h, the low concentration inhibited cell proliferation while the 500 μg/mL extracts stimulated cell proliferation. Morphological changes were observed in cells incubated with Chinese kernel extracts after 24 h and South African kernel treatment (1000 μg/mL) after 72 h. A possible intra-S-phase block after 24 and 48 h exposure to South African hydrophilic kernel extracts was observed. This transient block that is more concerned with tolerating and accommodating damage during replication rather than repairing it, could explain the initial anti-proliferative effects observed after 24 h exposure to the various Chinese kernel extract concentrations.
CONCLUSION: Abrogation of the block by exhaustion of the cyanide production, most likely allowed the cells to resume the cell cycle and continue into mitosis, whereas low ATP levels caused by the presence of amygdalin in the kernels, can also cause the induction of pycnosis or necrosis. These results highlight the possible mechanisms of growth inhibition by amygdalin containing extracts and may contribute towards the development of dietary anti-cancer therapies.

Alcolea V, Karelia DN, Pandey MK, et al.
Identification of a Novel Quinoxaline-Isoselenourea Targeting the STAT3 Pathway as a Potential Melanoma Therapeutic.
Int J Mol Sci. 2019; 20(3) [PubMed] Article available free on PMC after 01/04/2020 Related Publications
The prognosis for patients with metastatic melanoma remains very poor. Constitutive signal transducer and activator of transcription 3 (STAT3) activation has been correlated to metastasis, poor patient survival, larger tumor size, and acquired resistance against vemurafenib (PLX-4032), suggesting its potential as a molecular target. We recently designed a series of isoseleno- and isothio-urea derivatives of several biologically active heterocyclic scaffolds. The cytotoxic effects of lead isoseleno- and isothio-urea derivatives (compounds 1 and 3) were studied in a panel of five melanoma cell lines, including B-RAF

Jiang X, Finucane HK, Schumacher FR, et al.
Shared heritability and functional enrichment across six solid cancers.
Nat Commun. 2019; 10(1):431 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r

Elansary HO, Szopa A, Kubica P, et al.
Phenolic Compounds of
Molecules. 2019; 24(3) [PubMed] Article available free on PMC after 01/04/2020 Related Publications
Tree bark represents an important source of medicinal compounds that may be useful for cancer therapy. In the current study, high-performance liquid chromatography with diode-array detection (HPLC-DAD) was used to determine the profile of the phenolic compounds of

Sibiya MA, Raphoko L, Mangokoana D, et al.
Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol.
Molecules. 2019; 24(3) [PubMed] Article available free on PMC after 01/04/2020 Related Publications
Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising targeted and selective anticancer drug activity. Hence, this study was aimed at determining in vitro anticancer activity effects of a newly synthesized class of 3-(quinoxaline-3-yl) prop-2-ynyl quinoxaline derivatives on A549 lung cancer cells. An assessment of the quinoxaline derivatives ferric reducing power, free radical scavenging activity, cytotoxic activity, and ability to induce reactive oxygen species (ROS) production was performed using the Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluorescein diacetate (H₂DCFDA) assays, respectively. The ability of the quinoxaline derivatives to induce apoptosis in A549 cells was assessed using the Acridine Orange/Ethidium Bromide (AO/EB) and Annexin V-FITC/Dead Cell Assay. Of the four quinoxaline derivatives tested, 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate (LA-39B) and 3-(quinoxaline-3-yl) prop-2-yn-1-ol (LA-55) displayed a dose-dependent reducing power, free-radical scavenging activity, inhibition of cell viability, and stimulation of ROS production which was accompanied by induction of apoptosis in A549 lung cancer cells. None of the quinoxaline derivatives induced cell death or ROS production in non-cancerous Raw 267.4 macrophage cells. Cytotoxicity was observed in A549 lung cancer, HeLa cervical cancer, and MCF-7 breast cancer cells albeit inhibition was more pronounced in A549 cells. The results of the study suggest that 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate and 3-(quinoxaline-3-yl) prop-2-yn-1-ol induce apoptotic cell death in A549 lung cancer cells.

Bhatla N, Berek JS, Cuello Fredes M, et al.
Revised FIGO staging for carcinoma of the cervix uteri.
Int J Gynaecol Obstet. 2019; 145(1):129-135 [PubMed] Related Publications
OBJECTIVE: To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent.
METHODS: Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations.
RESULTS: In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2-4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care.
CONCLUSION: The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions.

Cohen PA, Jhingran A, Oaknin A, Denny L
Cervical cancer.
Lancet. 2019; 393(10167):169-182 [PubMed] Related Publications
Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300 000 deaths worldwide. High-risk subtypes of the human papilloma virus (HPV) are the cause of the disease in most cases. The disease is largely preventable. Approximately 90% of cervical cancers occur in low-income and middle-income countries that lack organised screening and HPV vaccination programmes. In high-income countries, cervical cancer incidence and mortality have more than halved over the past 30 years since the introduction of formal screening programmes. Treatment depends on disease extent at diagnosis and locally available resources, and might involve radical hysterectomy or chemoradiation, or a combination of both. Conservative, fertility-preserving surgical procedures have become standard of care for women with low-risk, early-stage disease. Advances in radiotherapy technology, such as intensity-modulated radiotherapy, have resulted in less treatment-related toxicity for women with locally-advanced disease. For women with metastatic or recurrent disease, the overall prognosis remains poor; nevertheless, the incorporation of the anti-VEGF agent bevacizumab has been able to extend overall survival beyond 12 months. Preliminary results of novel immunotherapeutic approaches, similarly to other solid tumours, have shown promising results so far.

Feller L, Khammissa RAG, Bouckaert M, et al.
Pain: Persistent postsurgery and bone cancer-related pain.
J Int Med Res. 2019; 47(2):528-543 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
The generation of neuropathic pain is a complex dynamic process. Factors involved include one or more dysregulated sensory neural pathways; dysregulated activity of specific neurotransmitters, synapses, receptors and cognitive and emotional neural circuits; and the balance between degenerative and regenerative neural events. Risk factors include age, sex, cognition, emotions, genetic polymorphism, previous or ongoing chronic pain conditions and the use of certain drugs. Intense pain experienced before, during and after surgery is a risk factor for the development of central sensitization with consequent persistent postsurgery neuropathic pain. Blockade of N-methyl-D-aspartate receptors with appropriate drugs during and immediately after surgery may prevent persistent postsurgical pain. Most cancers, but particularly malignant metastases in bone, can induce persistent pain. Local factors including direct damage to sensory nerve fibres, infiltration of nerve roots by cancer cells and algogenic biological agents within the microenvironment of the tumour bring about central sensitization of dorsal horn neurons, characterized by neurochemical reorganization with persistent cancer pain. In this article, the clinical features, pathogenesis and principles of management of persistent postsurgery pain and cancer pain are briefly discussed.

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