Treatment delays for cancer patients in Sub-Saharan Africa: South Africa as a microcosm.

Purpose: Delays in initiating cancer treatment time to treatment initiation (TTI) can negatively impact patient outcomes. This study aimed to quantify the association between TTI and survival in breast, cervical and prostate cancer patients at Inkosi Albert Luthuli Central Hospital (IALCH) in KwaZulu-Natal, South Africa, as a microcosm of Sub-Saharan Africa (SSA).

Methods: We analyzed electronic medical records of patients diagnosed with breast, cervical or prostate cancer at IALCH between 2010 and 2020.

Long-term effects of aromatase inhibitors on body mass index among postmenopausal breast cancer survivors in Africa: observational cohort study.

Purpose: this study was conducted to assess the impact of AIs on body mass index and high sensitivity as prognostic predictors to be incorporated into point of care technology (POCT) testing in postmenopausal breast cancer women after a 24 month follow up in Africa. An observational cohort study was conducted; including 126 female BC patients with stages ranging from 0-III initially subjected to AIs and subsequently followed up for 24 months. Multiple imputation model was conducted to predict missing data.

The Role of Positron Emission Tomography and Computed Tomographic (PET/CT) Imaging for Radiation Therapy Planning: A Literature Review.

PET/CT is revolutionising radiotherapy treatment planning in many cancer sites. While its utility has been confirmed in some cancer sites, and is used in routine clinical practice, it is still at an experimental stage in many other cancer sites. This review discusses the utility of PET/CT in cancer sites where the role of PET/CT has been established in cases such as head and neck, cervix, brain, and lung cancers, as well as cancer sites where the role of PET/CT is still under investigation such as uterine, ovarian, and prostate cancers.

Feasibility of point of care testing for prevention and management of breast cancer therapy associated comorbidities in 6 African countries: short communication.

Objective: Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer (BC) survivors using aromatase inhibitors (AIs). This study was conducted to assess the impact of point of care technology (PCOT) as part of pathology supported genetic testing (PSGT) to prevent BC therapy-associated comorbidities in African settings.

Results: The study revealed that high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) are predictors of cardiovascular (CVD) related adverse events in obese postmenopausal patients subjected to AIs.

, and as potential drug targets for radiosensitizing cancer cell lines.

Background And Purpose: Activation of some signaling pathways can promote cell survival and have a negative impact on tumor response to radiotherapy. Here, the role of differences in expression levels of genes related to the poly(ADP-ribose) polymerase-1 (PARP-1), heat shock protein 90 (Hsp90), B-cell lymphoma 2 (Bcl-2), and phosphoinositide 3-kinase (PI3K) pathways in the survival or death of cells following X-ray exposure was investigated.

Methods: Eight human cell cultures (MCF-7 and MDA-MB-231: breast cancers; MCF-12A: apparently normal breast; A549: lung cancer; L132: normal lung; G28, G44 and G112: glial cancers) were irradiated with X-rays.

Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells.

Cancer continues to be a growing burden, especially in the resource limited regions of the world, and more effective and affordable therapies are highly desirable. In this study, the effect of X-ray irradiation and four inhibitors, viz. those against epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2) was evaluated in lung, breast, and cervical cancer cell lines, including normal cell lines to determine and compare the potential therapeutic benefit of these treatment modalities.

Chemotherapy for elderly colorectal cancer patients at a tertiary hospital in South Africa.

Introduction: surgical treatment of colorectal cancer (CRC) in elderly patients has improved, but data on the tolerability and benefits of adjuvant and palliative chemotherapy in this growing population remains scarce.

Methods: we conducted a retrospective study to compare chemotherapy-associated toxicities in CRC patients aged < 70 years and ≥ 70 years at Tygerberg Hospital (South Africa). We also assessed tumor-related mortality, progression free survival (PFS), and overall survival (OS) including predictive factors of OS.

The malignancy index is a robust predictor of prostate cancer.

The objective of this study was to validate the results from our published work and to test the robustness of our unique malignancy index as a (non-invasive) predictor of prostate cancer in fresh blood samples obtained from patients diagnosed with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and healthy volunteers (Controls). The malignancy index was obtained by dividing the product of three biomarker values, [urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1), and prostate-specific antigen (PSA)], by the age of the patient/healthy volunteer, using enzyme-linked immunosorbent (ELISA) assay methodology. The results confirmed earlier findings that the malignancy index discriminates prostate cancer from non-prostate cancer.

A preliminary study on treatment of human breast cancer xenografts with a cocktail of paclitaxel, doxorubicin, and I-anti-epithelial cell adhesion molecule (9C4).

Triple-negative breast cancer often has devastating outcomes and treatment options remain limited. Therefore, different treatment combinations are worthy of testing. The efficacy of a cocktail of paclitaxel, doxorubicin, and I-anti-epithelial cell adhesion molecule (EpCAM) (9C4) to treat breast cancer was tested.

The malignancy index in plasma samples as a prostate cancer biomarker.

No unambiguous role of the involvement of uroplasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in prostate cancer has emerged, with current evidence suggesting that neither biomarker is likely of significant clinical value, save as an overall contributor. In this study, we attempt to discriminate prostate cancer from non-cancer in a cohort of plasma samples, using the Imubind ELISA assay. In this cohort, PAI-1 levels are higher in prostate cancer patients than healthy donors; uPA levels are higher in healthy donors than prostate cancer patients; and the uPA/PAI-1 ratio is higher in healthy donors than in prostate cancer patients.

Towards Establishing Capacity for Biological Dosimetry at Ghana Atomic Energy Commission.

The aim of this study was not only to obtain basic technical prerequisites for the establishment of capacity of biological dosimetry at the Ghana Atomic Energy Commission (GAEC) but also to stimulate interest in biological dosimetry research in Ghana and Sub-Saharan Africa. Peripheral blood from four healthy donors was exposed to different doses (0-6 Gy) of gamma rays from a radiotherapy machine and lymphocytes were subsequently stimulated, cultured, and processed according to standard protocols for 48-50 h. Processed cells were analyzed for the frequencies of dicentric and centric ring chromosomes.

Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells.

Targeting pro-survival cell signaling components has been promising in cancer therapy, but the benefit of targeting with single agents is limited. For malignancies such as triple-negative breast cancer, there is a paucity of targets that are amenable to existing interventions as they are devoid of the human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER). Concurrent targeting of cell signaling entities other than HER2, PR and ER with multiple agents may be more effective.

Flow cytometry-assisted quantification of γH2AX expression has potential as a rapid high-throughput biodosimetry tool.

Large-scale radiological events require immediate and accurate estimates of doses received by victims, and possibly the first responders, to assist in treatment decisions. Although there are numerous efforts worldwide to develop biodosimetric tools to adequately handle triage needs during radiological incidents, such endeavours do not seem to actively involve sub-Saharan Africa which currently has a significant level of nuclear-related activity. To initiate a similar interest in Africa, ex vivo radiation-induced γH2AX expression in peripheral blood lymphocytes from fourteen healthy donors was assessed using flow cytometry.

Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion.

Damage to the gut mucosa is a probable contributory cause of death from ingested Po. Therefore, medical products are needed that can prevent, mitigate, and/or repair gastrointestinal (GI) damage caused by high-LET radiation emitted by Po. The present studies investigated the capacity of a diet highly enriched with vitamins A, C, and E (vitamin ACE) to protect against intestinal mucosal damage indicated by functional reductions in nutrient transport caused by orally ingested Po.

The advantage of antibody cocktails for targeted alpha therapy depends on specific activity.

Unlabelled: Nonuniform dose distributions among disseminated tumor cells can be a significant limiting factor in targeted α therapy. This study examines how cocktails of radiolabeled antibodies can be formulated to overcome this limitation.

Methods: Cultured MDA-MB-231 human breast cancer cells were treated with different concentrations of a cocktail of 4 fluorochrome-conjugated monoclonal antibodies.

Further evaluation of uPA and PAI-1 as biomarkers for prostatic diseases.

Purpose: To assay for uPA and PAI-1 in prostate tissue from 40 patients with prostatic disease and to examine the robustness of the correlation of the uPA/PAI-1 ratio with benign prostatic hyperplasia (BPH) and prostate cancer (PCa), previously identified in a different cohort of 62 patients.

Methods: uPA and PAI-1 were extracted from liquid N2 frozen homogenised prostate tissue with TRIS/Triton pH 8.5 buffer and measured by ELISA (FEMTELLE).

uPA/PAI-1 ratios distinguish benign prostatic hyperplasia and prostate cancer.

Purpose: Urokinase plasminogen activator (uPA) and its inhibitor type 1 (PAI-1) are associated with tumour metabolism and are widely considered to be informative for the identification of cancer. We have analysed prostate tissue resections from patients with prostate cancer (PCa) and with benign prostatic hyperplasia (BPH) for protein levels of uPA and PAI-1, and searched for distinctions between these two clinical manifestations.

Methods: Prostate tissue was deep frozen in liquid N2 and homogenized in a stainless steel punch homogenizer.

In vitro radiosensitization by pentoxifylline does not depend on p53 status.

Purpose: The mode by which the xanthine derivative, pentoxifylline, induces a radiosensitizing effect in cell cultures is a key and controversial radiobiological issue and requires further elucidation.

Materials And Methods: Six human glioblastoma cell lines were tested for the effect of pentoxifylline treatment at maximum G2/M block on the basis of cell survival, mitotic activity, and micronucleus formation after exposure to gamma radiation. Cell survival was measured by the colony-forming assay.

A method to predict response of cell populations to cocktails of chemotherapeutics and radiopharmaceuticals: validation with daunomycin, doxorubicin, and the alpha particle emitter (210)Po.

Unlabelled: There is considerable interest in the use of α-emitting radionuclides in radioimmunotherapy. However, the high toxicity of α-emitting radionuclides often does not permit administration of high activities for fear of normal tissue toxicity. Accordingly, targeting procedures need to be optimized for improved tumor control and minimized normal tissue toxicity.

Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype.

Purpose: This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with (125)I-labeled 5-iodo-2 -deoxyuridine ((125)IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner.

Materials And Methods: In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold.

Flow cytometry-assisted Monte Carlo simulation predicts clonogenic survival of cell populations with lognormal distributions of radiopharmaceuticals and anticancer drugs.

Purpose: Although the distribution of therapeutic agents within cell populations may appear uniform at the macroscopic level, the distribution at the multicellular level is nonuniform. As such, the mean agent concentration in tissue may not be a suitable quantity for use in predicting biological effects. Failure in chemotherapy and targeted radionuclide therapy has been attributed, in part, to the ubiquity of lognormal distributions of therapeutic agents.

Changes in lognormal shape parameter guide design of patient-specific radiochemotherapy cocktails.

Unlabelled: Uptake of radiopharmaceuticals and chemotherapeutic drugs is nonuniform at the microscopic level. Their distributions are typically lognormal, suggesting that failure in chemotherapy and targeted radionuclide therapy may be attributable, in part, to the characteristics of this biologically ubiquitous distribution. The lognormal problem can be overcome by using cocktails of 2 or more agents, tailored such that at least 1 agent is strongly incorporated by every cell in the target population.

Wound healing morbidity in STS patients treated with preoperative radiotherapy in relation to in vitro skin fibroblast radiosensitivity, proliferative capacity and TGF-beta activity.

Background And Purpose: In a recent study, we demonstrated that the ability of dermal fibroblasts, obtained from soft tissue sarcoma (STS) patients, to undergo initial division in vitro following radiation exposure correlated with the development of wound healing morbidity in the patients following their treatment with preoperative radiotherapy. Transforming growth factor beta (TGF-beta) is thought to play an important role in fibroblast proliferation and radiosensitivity both of which may impact on wound healing. Thus, in this study we examined the interrelationship between TGF-beta activity, radiosensitivity and proliferation of cultured fibroblasts and the wound healing response of STS patients after preoperative radiotherapy to provide a validation cohort for our previous study and to investigate mechanisms.

Clonogenic survival and cytokinesis-blocked binucleation of skin fibroblasts and normal tissue complications in soft tissue sarcoma patients treated with preoperative radiotherapy.

Background And Purpose: To evaluate the clonogenic and cytokinesis-blocked assays in skin fibroblast cultures for their utility as tools for predicting normal tissue responses in soft tissue sarcoma (STS) patients treated with preoperative radiotherapy.

Patients And Methods: Dermal fibroblast strains were established from skin biopsies of 26 STS patients who received preoperative radiotherapy. Cultures were subjected to the colony forming and cytokinesis-blocked assays after low (approximately 0.