Browsing by Subject "cancer"

Now showing 1 - 5 of 5
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    Open Access
    A 40-50kDa Glycoprotein Associated with Mucus is Identified as α-1-Acid Glycoprotein in Carcinoma of the Stomach
    (2012) Chirwa, Nthato; Govender, Dhirendra; Ndimba, Bongani; Lotz, Zoe; Tyler, Marilyn; Panieri, Eugenio; KAHN, DELAWIR; Mall, Anwar S
    Background and Aim: Secreted gastric mucins are large O-glycosylated proteins of crude mucus gels which are aberrantly expressed in malignancy. An albumin associated 55-65kDa glycoprotein was previously shown in mucus gels in gastric cancer. The aim of this study was to investigate its expression and identification in human gastric tissue. Methods: Mucins were purified from crude mucus scrapings of 16 partial and 11 total resections and a rabbit polyclonal antibody was raised to the 55-65kDa glycoprotein. The location and expression of the glycoprotein was examined in normal gastric mucosa (n=20), intestinal metaplasia (n=18) and gastric cancer (n=27) tissue by immunohistochemistry. Mucins were analyzed by isoelectric focusing (IEF) on 2-D polyacrylamide gels. Identification of the 40-50kDa glycoprotein was by MALDI-TOF MS technique. Plasma levels were examined by Western blotting. Results: Extensive SDS-PAGE analysis gave a PAS positive glycoprotein in the 40-50kDa range, in patients with gastric cancer but not normals. It was expressed in parietal and columnar cells of normal gastric tissue and intestinal metaplasia respectively, and in 22 of 27 gastric cancer specimens. In 2-D PAGE stained with Coomassie Blue there were 3 spots positively identified as alpha-1-acid glycoprotein (AGP) by MALDI-TOF MS technique. PAS staining revealed a single bright spot in the same position but could not be identified. Preliminary measurements showed slightly higher levels of AGP in plasma of patients with gastric carcinoma. Conclusion: AGP levels are increased in gastric tissue and in the plasma of those with carcinoma of the stomach.
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    Acetaldehyde Adducts in Alcoholic Liver Disease
    (2010) Setshedi, Mashiko; Wands, Jack R; de la Monte, Suzanne M
    Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD), with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC). Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15%) versus cirrhosis (15–20%) is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.
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    Design and development of a speculum-free digital cervical cancer screening device
    (2024) Hefer, Lehan; Sivarasu, Sudesh; Saidu, Rakiya
    Introduction Cervical cancer poses a significant global health challenge, particularly in low- and middle income countries (LMICs), where the disease remains a leading cause of cancer-related deaths among women. Despite the success of cytology-based screening programs in developed nations, implementing effective screening in resource-constrained environments has proven challenging. Visual Inspection with Acetic acid (VIA), a cost-effective alternative, has limitations due to subjective diagnosis, hindering large scale implementation. This research addresses the need for improved cervical cancer screening in LMICs through the design and development of a speculum-free digital screening device. Recognising the potential of digital technology to enhance VIA's diagnostic accuracy, the project aims to create a device that combines the simplicity and cost-effectiveness of VIA with digital advancements. This research aims to develop a speculum-free cervical cancer screening device that matches the diagnostic accuracy of the standard screening tool while enhancing usability. The objectives include the development of the device, verification guided by ISO 8600 standards for medical endoscopes and ISO 14971 risk assessment, and validation of the developed device's diagnostic performance and usability through a simulated clinical study. Materials and Methods The design and development of the cervical cancer screening device, the CerviScreen, used rapid prototyping and testing principles. Comprising five subsystems—housing, visualisation, liquid application, dilation, and decontamination—the subsystems were independently designed and subsequently integrated. The dilation subsystem, developed to enable speculum-free screening, simplifies the screening process and prioritises patient comfort. The device offers a less invasive screening procedure, providing real-time video images, controllable lights, and an acetic acid application system for cleaning the cervix and inducing the acetowhitening effect for diagnosis. The first verification phase tested the dilation subsystem's compliance with engineering specifications and selected the optimal dilation cup design. Subsequently, the complete device underwent verification using tests aligned with ISO 8600 standards and auxiliary tests done by predicate devices. The second verification phase assessed the risk of the device to identify and mitigate usability and functionality risks. Validation involved simulating a cervical cancer screening procedure using a female pelvic training model in a gynaecology clinic. This comparative study assessed the CerviScreen's diagnostic accuracy against the colposcope, with experienced gynaecologists conducting diagnoses, as well as the usability of the device. Ethics approval (Reference number: HREC REF 570/2023) was obtained for this validation study. Results and Analysis Five experienced gynaecologists from Groote Schuur Hospital participated in the study, averaging 14±7.01 years of experience. The CerviScreen and colposcope demonstrated a diagnostic accuracy of 80%, indicating comparable accuracy. Usability, measured by the System Usability Score (SUS), scored 83.75, indicating 'good' usability. Post-test feedback from the participants reflected positive perceptions regarding device usability and features. Conclusion The speculum-free digital cervical cancer screening device fulfilled all design requirements to complete an entire screening procedure. It was validated to have diagnostic accuracy equivalent to that of the standard device and good usability in the simulated screening environment. While the validation testing strength lay in utilising highly experienced gynaecologists, limitations arose from inaccuracies introduced by the simplified anatomy and pathology of the female pelvic model and cervices. Despite positive results and feedback, future testing on more accurate human anatomy is essential to establish the device's efficacy. Ongoing work involves refining specific design aspects based on input from the validation study.
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    Medicine and the Arts Week 2 - My song for the living
    (2015-01-21) Hendricks, Marc
    In this video, paediatric oncologist Mark Hendricks discusses the intersections between music and healing in the context of caring for children with cancer in middle-income settings. He discusses the importance of listening to and understanding the individual needs of children, and he emphasizes the importance of family-centered care, with the need to consider the social and cultural context when caring for children with cancer. This is the second video in Week 2 of the Medicine and the Arts Massive Open Online Course.
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    The role of the tumour microenvironment components in cancer cell behaviour and drug response
    (2022) Senthebane, Dimakatso Alice; Parker, Mohamed Iqbal; Dzobo, Kevin
    Cancer is a public health burden which continues to cause many deaths and an economic burden worldwide. New and improved ways of thinking about anti-cancer drug design and development are needed now and in future. Recent reports demonstrate the key role played by the tumour microenvironment (TME) in tumour progression and the development of drug resistance. This study investigated the interactions between cancer cells and the stroma within the TME, specifically fibroblasts, mesenchymal stem cells (MSC), cancer stem cells (CSCs) as well as the extracellular matrix (ECM), with the goal to develop an in vitro model that mimics solid tumours in terms of cellular characteristics and drug response. Mesenchymal stem cells were investigated as potential sources of cancer-associated fibroblasts (CAFs) in solid tumours. The expression of CAFs markers, α-SMA and vimentin, increased significantly in MSCs co-cultured with oesophageal and breast cancer cells indicating conversion of MSCs into cell-like CAFs. WHCO1 (oesophageal) and MDA MB 231 (breast) cancer cells co-cultured with MSCs survived paclitaxel and cisplatin treatments better than cancer cells alone. To assess the prognostic value of CSCs, the expression and malignant behaviour of CSC markers were also examined in clinicopathologically-confirmed oesophageal cancer biopsies and in vitro. Oesophageal cancer biopsies stained strongly for the cancer stem cell markers, CD44 and ALDH1A1, demonstrating the presence of CSCs in these tumours. FACS-isolated side population cells exhibited high levels of cancer stem cell markers, self-renewal markers and drug resistance proteins and were associated with increased drug resistance versus cancer cells. In order to measure how ECM proteins affect oesophageal cancer cell response to chemotherapeutic drugs, 3D cell-derived ECMs was used as a model. The analysis of ECM proteins using qRT-PCR in oesophageal cancer biopsies showed that collagens, fibronectin, and laminins were overexpressed in tumour tissue compared with adjacent normal tissues. The culture of cancer cells on decellularised ECMs reduced the effect of drugs on cancer cells compared to those plated on plastic (control). The reduction of the effects of drugs was associated with significant activation of survival signalling pathways. Knockdown of collagen and fibronectin with siRNA combined with drugs resulted in increased sensitivity of cancer cells to drugs and lower colony formation and cancer cell migration. Lastly, this study utilized multi-cell tumour spheroids (MCTS) from WHCO1 and MDA MB 231 cells co-cultured with WI38 and CT1 fibroblasts to mimic tumour cell-stromal cell interactions as observed within the in vivo tumour microenvironment. The data show that spheroids were more resistant to drugs than monolayer cultures of the same cells. MCTS displayed characteristics similar to in vivo tumours in terms of response to drugs. Associated with these findings were increased levels of CSCs in MCTS compared to monolayer. This study demonstrated that MSCs are a possible source of ‘CAFs' in vivo and can support cancer cell growth. This study also demonstrated the presence of CSCs in tumours and that the targeting of these cells can shrink tumours and prevent potential metastasis and relapse of tumours. This study revealed that ECM proteins play major roles in the response of cancer cells to chemotherapy and suggest that targeting ECM proteins, especially type I collagen and fibronectin, can be an effective therapeutic strategy against chemoresistant tumours. MCTS, as shown in this study, is a valuable tool for the evaluation of the therapeutic effect of drugs. Overall, this study demonstrates the critical role played by the tumour microenvironment in tumour growth and metastasis and provides new insights into cancer treatment.