Search results for: Breast Cancer

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Jemini Vyas, Oluwatobi Adeyoe, Jenny Branagan, Chandran Tanabalan, Aakash Pai

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Introduction: Radical prostatectomy and radiotherapy are both viable options for the treatment of localised prostate cancer. Over the years medicine has evolved towards a patient-centred approach. Patient decision-making is not motivated by clinical outcomes alone. Geographical location and ease of access to treating clinician are contributory factors. With the development of robotic surgery, prostatectomy has been centralised into tertiary centres. This has impacted on the distances that patients and their families are expected to travel. Methods: A single centre retrospective study was undertaken over a five-year period. All patients with localised prostate cancer, undergoing radical radiotherapy or prostatectomy were collected pre-centralisation. This was compared to the total number undergoing these treatments post centralisation. Results: Pre-centralisation, both radiotherapy and prostatectomy groups had to travel a median of less than five miles for treatment. Post-centralisation of pelvic surgery, prostatectomy patients had to travel a median of more than 40 miles, whilst travel distance for the radiotherapy group was unchanged. In the post centralisation cohort, there was a 63% decline in the number of patients undergoing radical prostatectomy per month from a mean of 5.1 to 1.9. The radical radiotherapy group had a concurrent 41% increase in patient numbers with a mean increase from 13.3 to 18.8 patients per month. Conclusion: Choice of radical treatment in localised prostate cancer is based on multiple factors. This study infers that local availability can influence choice of radical treatment. It is imperative that efforts are made to maintain accessibility to all viable options for prostate cancer patients, so that patient choice is not compromised.

Keywords: prostate, prostatectomy, radiotherapy, centralisation

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Authors: Desi Meriyanti, Delina Puspa Rosana Firdaus, Ristia Rinati

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Nowadays, the presence of free radicals become a big concern due to its negative impact to the body, which can triggers the formation of degenerative diseases such as cancer, heart disease cardiovascular, diabetic mellitus and others. Free radical oxidation can be prevented by the presence of antioxidants. Naturally, the human body produces its own antioxidants. Because of the free radicals exposure are so intense, especially from the environment, it is necessary to supply antioxidants needed from outside, through the consumption of functional foods with high antioxidant content. Gethuk is one of the traditional snacks in Indonesia. Gethuk is made from cassava with minimal processing such as boiling, destructing, and forming. Gethuk is classified as a familiar snack in the community, so it has a potential for developing, especially into a functional food. The low content of antioxidants in gethuk can be overcome with the development of a product called Gethuk Marillo. Gethuk Marillo is gethuk with the addition of natural antioxidants from mangosteen pericarp extract which has a high content of xanthones, these compounds are classified into flavonoids and act as antioxidants in the body. Gethuk Marillo served along with tamarillo fruit sauce which is also high in antioxidants such as anthocyanin. The combination between 300 grams gethuk Marillo and sauce contain flavonoid about 31% of human antioxidant needs per day. Gethuk Marillo called as a functional food because of high flavonoids content which can prevent degenerative diseases namely cancer, as many studies that the xanthone and anthocyanins compounds can effectively prevent the formation of cancer cells in human body.

Keywords: Gethuk marillo, xanthones, anthocyanin, high antioxidants, anti-cancer

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Authors: Syue-Wen Lin

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Objective: This article explores the nursing experience of a 64-year-old female lung cancer patient who underwent a thoracoscopic left lower lobectomy and treatment. The patient has a history of diabetes. The nursing process included cancer treatment, postoperative pain management, wound care and healing, and family grief counseling. Methods: The nursing period is from March 11 to March 15, 2024. During this time, strict aseptic wound dressing procedures and advanced wound care techniques are employed to promote wound healing and prevent infection. Postoperatively, due to the development of aspiration pneumonia and worsening symptoms, re-intubation was necessary. Given the patient's advanced cancer and deteriorating condition, the nursing team provided comprehensive grief counseling and care tailored to both the patient's physical and psychological needs, as well as the emotional needs of the family. Considering the complexity of the patient's condition, including advanced cancer, palliative care was also integrated into the overall nursing process to alleviate discomfort and provide psychological support. Results: Using Gordon's Functional Health Patterns for assessment, including evaluating the patient's medical history, physical assessment, and interviews, to provide individualized nursing care, it is important to collect data that will help understand the patient's physical, psychological, social, and spiritual dimensions. The interprofessional critical care team collaborates with the hospice team to help understand the psychological state of the patient's family and develop a comprehensive approach to care. Family meetings should be convened, and support should be provided to patients during the final stages of their lives. Additionally, the combination of cancer care, pain management, wound care, and palliative care ensures comprehensive support for the patient throughout her recovery, thereby improving her quality of life. Conclusion: Lung cancer and aspiration pneumonia present significant challenges to patients, and the nursing team not only provides critical care but also addresses individual patient needs through cancer care, pain management, wound care, and palliative care interventions. These measures have effectively improved the quality of life of patients, provided compassionate palliative care to terminally ill patients, and allowed them to spend the last mile of their lives with their families. Nursing staff work closely with families to develop comprehensive care plans to ensure patients receive high-quality medical care as well as psychological support and a comfortable recovery environment.

Keywords: grief counseling, lung cancer, palliative care, nursing experience

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Authors: Andrew Anis Fakhrey Mosaad

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The goal of this study is to compare the efficacy of polarised light therapy with low-intensity laser therapy in treating oral mucositis brought on by chemotherapy in cancer patients. Evaluation procedures are the measurement of the WHO oral mucositis scale and the Common toxicity criteria scale. Techniques: Cancer patients (men and women) who had oral mucositis, ulceration, and discomfort and whose ages varied from 30 to 55 years were separated into two groups and received 40 chemotherapy treatments. Twenty patients in Group (A) received low-level laser therapy (LLLT) along with their regular oral mucositis medication treatment, while twenty patients in Group (B) received Bioptron light therapy (BLT) along with their regular oral mucositis medication treatment. Both treatments were applied for 10 minutes each day for 30 days. Conclusion and results: This study showed that the use of both BLT and LLLT on oral mucositis in cancer patients following chemotherapy greatly improved, as seen by the sharp falls in both the WHO oral mucositis scale (OMS) and the common toxicity criteria scale (CTCS). However, low-intensity laser therapy (LLLT) was superior to Bioptron light therapy in terms of benefits (BLT).

Keywords: Bioptron light therapy, low level laser therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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Authors: Maksim Barsakov

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Introduction. In modern plastic surgery, there are a large number of breast lift techniques.Due to the spreading information about the "side effects" of silicone implants, interest in implant-free mastopexy is increasing year after year. However, despite the variety of techniques, patients sometimes do not get full satisfaction from the results of mastopexy because of the unexpressed filling of the upper pole, extended anchoring postoperative scars and sometimes because of obtaining an aesthetically unattractive breast shape. The stability of the result after mastopexy depends on many factors, including postoperative rehabilitation. Stability of weight and hormonal background, stretchability of tissues. The high recurrence rate of ptosis and short-term aesthetic effect of mastopexy indicate the urgency of improving surgical techniques and increasing the stabilization of breast tissue. Purpose of the study. To develop and introduce into practice a technique of mastopexy based on the use of a modified Ribeiro flap, as well as elements of tissue movement and fixation designed to increase the stability of postoperative mastopexy. In addition, to give indications for the application of this surgical technique. Materials and Methods. it operated on 103 patients aged 18 to 53 years from 2019 to 2023 according to the reported method. These were patients with primary mastopexy, secondary mastopexy, and also patient with implant removal and one-stage mastopexy. The patients were followed up for 12 months to assess the stability of the result. Results and their discussion. Observing the patients, we noted greater stability of the breast shape and upper pole filling compared to the conventional classical methods. We did not have to resort to anchoring scars. In 90 percent of cases, a inverted T-shape scar was used. In 10 percent, the J-scar was used. The quantitative distribution of complications identified among the operated patients is as follows: worsened healing of the junction of vertical and horizontal sutures at the period of 1-1.5 months after surgery - 15 patients; at treatment with ointment method healing was observed in 7-30 days; permanent loss of NAC sensitivity - 0 patients; vascular disorders in the area of NAC/areola necrosis - 0 patients; marginal necrosis of the areola-2 patients. independent healing within 3-4 weeks without aesthetic defects. Aesthetically unacceptable mature scars-3 patients; partial liponecrosis of the autoflap unilaterally - 1 patient. recurrence of ptosis - 1 patient (after weight loss of 12 kg). In the late postoperative period, 2 patients became pregnant, gave birth, and no lactation problems were observed. Conclusion. Thus, in the world of plastic surgery methods of breast lift continue to improve, which is especially relevant in modern times, due to the increased attention to this operation. The author's proposed method of mastopexy with glandular autoflap allows obtaining in most cases a stable result, a fuller breast shape, avoiding the presence of extended anchoring scars, and also preserves the possibility of lactation. The author of this article has obtained a patent for invention for this method of mastopexy.

Keywords: mastopexy, mammoplasty, autoflap, personal technique

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Authors: Magdalena Twaruzek, Karolina Ropejko

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Mycotoxins are secondary metabolites of molds. Ochratoxin A (OTA) is the most common in the Polish climate. It is produced by fungi of the genera Aspergillus and Penicillium. It is produced as a result of improper food storage. It is present in many products that are consumed both by humans and animals: cereals, wheat gluten, coffee, dried fruit, wine, grape juice, spices, beer, and products based on them. OTA is nephrotoxic, hepatotoxic, potentially carcinogenic, and teratogenic. OTA mainly enters an organism by oral intake. The aim of the study was to detect the presence of OTA in milk, urine, and serum of lactating women. A survey was also conducted regarding the daily diet of women. The research group consisted of 32 lactating women (11 were the donors from the Milk Bank in Toruń, the other 21 were recruited for this study). Results of the analysis showed the occurrence of OTA only in 3 milk samples (9.38%). The minimum level was 0.01 ng/ml, while the maximum 0.018 ng/ml and the mean 0.0013 ng/ml. Twenty-six urine samples (81.25%) were OTA positive, with minimum level 0.013 ng/ml, maximum level 0.117 ng/ml and mean 0.0192 ng/ml. Also, all 32 serum samples (100%) were contaminated by OTA, with a minimum level of 0.099 ng/ml, a maximum level of 2.38 ng/ml, and a mean of 0.4649 ng/ml. In the case of 3 women, OTA was present in all tested body fluids. Based on the results, the following conclusions can be drawn: the breast-milk of women in the study group is slightly contaminated with ochratoxin A. Ten samples of urine contained ochratoxin A above its average content in tested samples. Moreover, serum of 8 women contains ochratoxin A at a level above the average content of this mycotoxin in tested samples. The average ochratoxin A level in serum in the presented studies was 0.4649 ng/ml, which is much lower than the average serum ochratoxin A level established in several countries in the world, i.e., 0.7 ng/ml. Acknowledgment: This study was supported by the Polish Minister of Science and Higher Education under the program 'Regional Initiative of Excellence' in 2019 - 2022 (Grant No. 008/RID/2018/19).

Keywords: breast-milk, urine, serum, contamination, ochratoxin A

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Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

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Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: biological molecular networks, essential genes, graph theory, network subgraphs

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Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

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The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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Authors: Mutaz Dwairy

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Solid tumors have high interstitial fluid pressure (IFP), high mechanical stress, and low oxygen levels. Solid stresses may induce apoptosis, stimulate the invasiveness and metastasis of cancer cells, and lower their proliferation rate, while oxygen concentration may affect the response of cancer cells to treatment. Although tumors grow in a nonhomogeneous environment, many existing theoretical models assume homogeneous growth and tissue has uniform mechanical properties. For example, the brain consists of three primary materials: white matter, gray matter, and cerebrospinal fluid (CSF). Therefore, tissue inhomogeneity should be considered in the analysis. This study established a physical model based on convection-diffusion equations and continuum mechanics principles. The model considers the geometrical inhomogeneity of the brain by including the three different matters in the analysis: white matter, gray matter, and CSF. The model also considers fluid-solid interaction and explicitly describes the effect of mechanical factors, e.g., solid stresses and IFP, chemical factors, e.g., oxygen concentration, and biological factors, e.g., cancer cell concentration, on growing tumors. In this article, we applied the model on a brain tumor positioned within the white matter, considering the brain inhomogeneity to estimate solid stresses, IFP, the cancer cell concentration, oxygen concentration, and the deformation of the tissues within the neoplasm and the surrounding. Tumor size was estimated at different time points. This model might be clinically crucial for cancer detection and treatment planning by measuring mechanical stresses, IFP, and oxygen levels in the tissue.

Keywords: biomechanical model, interstitial fluid pressure, solid stress, tumor microenvironment

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Authors: Aditya Manna, L. K. Khanra, S. K. Sarkar

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Aim: Due to financial incapability and the absence of manpower-poor families often fail to carry their advanced cancer patients to the nodal centers. This pilot study will explore whether communication by mobile phone can lessen this burden. Method: Initially a plan was generated regarding management of an advanced cancer patient in a nodal center at District Head Quarter. Subsequently every two week a trained social worker attached to the nodal center will follow up and give necessary advice and emotional support to the patients and their families through their registered mobile phone number. Patient’s family were also encouraged to communicate with the team by phone in case of fresh complain and urgency in between. Results: Since initiation in January 2013, 193 cancer patients were contacted by mobile phone every two weeks to enquire about their difficulties. In 76% of the situation trained social workers could give necessary advice by phone regarding management of their physical symptoms. Moreover, patient’s family was really overwhelmed by the emotional support offered by the team over the phone. Only 24% of cancer patients have to attend the nodal center for expert advice from Palliative Care specialists. Conclusion: This novel approach helped: (a) In providing regular physical and emotional support to the patients and their families. (b) In significantly reducing the financial and manpower problems of carrying patients to the nodal units. (c) In improving the quality of life of patients by continuous guidance. More and more team members can take help of this new strategy for better communication and uninterrupted care.

Keywords: palliative care, terminal care, home based palliative care, rural india

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Authors: Kevser Cakmak, Adrián Montesano, Lourdes Artigas, Marta Salla, Clara Mateu

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The main objective of this research is to explore the relational letter writing technique as an intervention in couple therapy for reconnecting couples with their values and ethical preferences. This is a recently developed therapeutic tool within the framework of Narrative Therapy that consists of two interviews and a letter writing task, in which a meta-conversation between the relationship itself, the couple members, and the therapists is fostered. Although this specific therapeutic technique can be used within the therapy process, in this case study, it is used as a brief stand-alone narrative intervention for a middle age heterosexual couple breast cancer survivor. Couple’s relational and personal wellbeing was monitored before, during, and after the intervention by means of the dyadic adjustment and the clinical outcomes in routine evaluation-outcome measure, respectively. The couple showed a significant improvement after the intervention in both levels. The content of the letter writing exercises was qualitatively analysed to explore the reconstruction of their ethical values. Results from both methods are integrated in order to get an in-depth perspective of the newly developed tool. The potential of the letter writing technique as stand-alone and as adjunct brief intervention is discussed.

Keywords: couple therapy, narrative therapy, psychotherapy tool, relational letter writing

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Authors: Paula Buldres, Jorge Toledo

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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

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Authors: Fatimah Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: DNA-CK20, PCNA, P53, colon cancer

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Authors: Bibiana Matilde Bernal Gómez, Manuel Salvador Rodríguez Susa, Mildred Fernanda Lemus Perez

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In chlorinated drinking water, Haloacetic acids have been identified and are classified as disinfection byproducts originating from reaction between natural organic matter and/or bromide ions in water sources. These byproducts can be generated through a variety of chemical and pharmaceutical processes. The term ‘Total Haloacetic Acids’ (THAAs) is used to describe the cumulative concentration of dichloroacetic acid, trichloroacetic acid, monochloroacetic acid, monobromoacetic acid, and dibromoacetic acid in water samples, which are usually measured to evaluate water quality. Chronic presence of these acids in drinking water has a risk of cancer in humans. The detection of THAAs for the first time in 15 municipalities of Boyacá was accomplished in 2023. Aim is to describe the correlation between the levels of THAAs and digestive cancer in Tunja, a city in Colombia with higher rates of digestive cancer and to compare the risk across 15 towns, taking into account factors such as water quality. A research project was conducted with the aim of comparing water sources based on the geographical features of the town, describing the disinfection process in 15 municipalities, and exploring physical properties such as water temperature and pH level. The project also involved a study of contact time based on habits documented through a survey, and a comparison of socioeconomic factors and lifestyle, in order to assess the personal risk of exposure. Data on the levels of THAAs were obtained after characterizing the water quality in urban sectors in eight months of 2022. This, based on the protocol described in the Stage 2 DBP of the United States Environmental Protection Agency (USEPA) from 2006, which takes into account the size of the population being supplied. A cancer risk assessment was conducted to evaluate the likelihood of an individual developing cancer due to exposure to pollutants THAAs. The assessment considered exposure methods like oral ingestion, skin absorption, and inhalation. The chronic daily intake (CDI) for these exposure routes was calculated using specific equations. The lifetime cancer risk (LCR) was then determined by adding the cancer risks from the three exposure routes for each HAA. The risk assessment process involved four phases: exposure assessment, toxicity evaluation, data gathering and analysis, and risk definition and management. The results conclude that there is a cumulative higher risk of digestive cancer due to THAAs exposure in drinking water.

Keywords: haloacetic acids, drinking water, water quality, cancer risk assessment

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Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton

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The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Keywords: biodegradable, nanoparticle, polymer, thermoresponsive

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Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

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A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Ching-Yi Huang, Pi-Fen Cheng, Hui-Zhu Chen, Shi Ting Huang, Heng-Hua Wang

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This is a case of oral cancer after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap. The nursing period lasted From September 25 to October 3, 2017, through observation, interview, physical assessment, and medical record review, the author identified the following nursing problems: acute pain, impaired oral mucous membrane, and body image change. During the nursing period, the author provided individual and overall nursing care and established mutual trust through the use of empathy. Author listened and eased the patient's physical indisposition, such as wound pain, we use medications and acupuncture massage to relieve pain. However, for oral mucosa change caused by surgery, provide continuous and complete oral care and oral exercise training to improve oral mucosal healing and restore swallowing function. In the body-image changes, guided him to express his feeling after the body-image change, and enhanced support and from the family, and encouraged him to attend head and neck cancer survivor alliance which allowed the patient to accept the altered body image and reaffirm self-worth. Hopefully, through sharing this nursing experience will help to the nursing care quality of nursing care for oral cancer patients after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap.

Keywords: oral cancer, acute pain, impaired oral mucous membrane, body image change

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Authors: Suveen Kumar

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Oral cancer (OC) is the sixth most death causing cancer in world which includes tumour of lips, floor of the mouth, tongue, palate, cheeks, sinuses, throat, etc. Conventionally, the techniques used for OC detection are toluidine blue staining, biopsy, liquid-based cytology, visual attachments, etc., however these are limited by their highly invasive nature, low sensitivity, time consumption, sophisticated instrument handling, sample processing and high cost. Therefore, we developed biosensing chips for non-invasive detection of OC via CYFRA-21-1 biomarker. CYFRA-21-1 (molecular weight: 40 kDa) is secreted in saliva of OC patients which is a non-invasive biological fluid with a cut-off value of 3.8 ng mL-1, above which the subjects will be suffering from oral cancer. Therefore, in first work, 3-aminopropyl triethoxy silane (APTES) functionalized zirconia (ZrO2) nanoparticles (APTES/nZrO2) were used to successfully detect CYFRA-21-1 in a linear detection range (LDR) of 2-16 ng mL-1 with sensitivity of 2.2 µA mL ng-1. Successively, APTES/nZrO2-RGO was employed to prevent agglomeration of ZrO2 by providing high surface area reduced graphene oxide (RGO) support and much wider LDR (2-22 ng mL-1) was obtained with remarkable limit of detection (LOD) as 0.12 ng mL-1. Further, APTES/nY2O3/ITO platform was used for oral cancer bioseneor development. The developed biosensor (BSA/anti-CYFRA-21-1/APTES/nY2O3/ITO) have wider LDR (0.01-50 ng mL-1) with remarkable limit of detection (LOD) as 0.01 ng mL-1. To improve the sensitivity of the biosensing platform, nanocomposite of yattria stabilized nanostructured zirconia-reduced graphene oxide (nYZR) based biosensor has been developed. The developed biosensing chip having ability to detect CYFRA-21-1 biomolecules in the range of 0.01-50 ng mL-1, LOD of 7.2 pg mL-1 with sensitivity of 200 µA mL ng-1. Further, the applicability of the fabricated biosensing chips were also checked through real sample (saliva) analysis of OC patients and the obtained results showed good correlation with the standard protein detection enzyme linked immunosorbent assay (ELISA) technique.

Keywords: non-invasive, oral cancer, nanomaterials, biosensor, biochip

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Authors: Roni Ramon-Gonen, Amir Dori, Shahar Shelly

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Background and objectives: Healthcare professionals produce abundant textual information in their daily clinical practice. The extraction of insights from all the gathered information, mainly unstructured and lacking in normalization, is one of the major challenges in computational medicine. In this respect, text mining assembles different techniques to derive valuable insights from unstructured textual data, so it has led to being especially relevant in Medicine. Neurological patient’s history allows the clinician to define the patient’s symptoms and along with the result of the nerve conduction study (NCS) and electromyography (EMG) test, assists in formulating a differential diagnosis. Past medical history (PMH) helps to direct the latter. In this study, we aimed to identify relevant PMH, understand which PMHs are common among patients in the referral cohort and documented by the medical staff, and examine the differences by sex and age in a large cohort based on textual format notes. Methods: We retrospectively identified all patients with abnormal NCS between May 2016 to February 2022. Age, gender, and all NCS attributes reports were recorded, including the summary text. All patients’ histories were extracted from the text report by a query. Basic text cleansing and data preparation were performed, as well as lemmatization. Very popular words (like ‘left’ and ‘right’) were deleted. Several words were replaced with their abbreviations. A bag of words approach was used to perform the analyses. Different visualizations which are common in text analysis, were created to easily grasp the results. Results: We identified 5282 unique patients. Three thousand and five (57%) patients had documented PMH. Of which 60.4% (n=1817) were males. The total median age was 62 years (range 0.12 – 97.2 years), and the majority of patients (83%) presented after the age of forty years. The top two documented medical histories were diabetes mellitus (DM) and surgery. DM was observed in 16.3% of the patients, and surgery at 15.4%. Other frequent patient histories (among the top 20) were fracture, cancer (ca), motor vehicle accident (MVA), leg, lumbar, discopathy, back and carpal tunnel release (CTR). When separating the data by sex, we can see that DM and MVA are more frequent among males, while cancer and CTR are less frequent. On the other hand, the top medical history in females was surgery and, after that, DM. Other frequent histories among females are breast cancer, fractures, and CTR. In the younger population (ages 18 to 26), the frequent PMH were surgery, fractures, trauma, and MVA. Discussion: By applying text mining approaches to unstructured data, we were able to better understand which medical histories are more relevant in these circumstances and, in addition, gain additional insights regarding sex and age differences. These insights might help to collect epidemiological demographical data as well as raise new hypotheses. One limitation of this work is that each clinician might use different words or abbreviations to describe the same condition, and therefore using a coding system can be beneficial.

Keywords: abnormal studies, healthcare analytics, medical history, nerve conduction studies, text mining, textual analysis

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Authors: Maryam Haghi, Ivan Contreras, Nadia Bhuiyan

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Chemotherapy is one of the most popular and effective cancer treatments offered to patients in outpatient oncology centers. In such clinics, patients first consult with an oncologist and the oncologist may prescribe a chemotherapy treatment plan for the patient based on the blood test results and the examination of the health status. Then, when the plan is determined, a set of chemotherapy and consultation appointments should be scheduled for the patient. In this work, a comprehensive mathematical formulation for planning and scheduling different types of chemotherapy patients over a planning horizon considering blood test, consultation, pharmacy and treatment stages has been proposed. To be more realistic and to provide an applicable model, this study is focused on a case study related to a major outpatient cancer treatment clinic in Montreal, Canada. Comparing the results of the proposed model with the current practice of the clinic under study shows significant improvements regarding different performance measures. These major improvements in the patients’ schedules reveal that using optimization techniques in planning and scheduling of patients in such highly demanded cancer treatment clinics is an essential step to provide a good coordination between different involved stages which ultimately increases the efficiency of the entire system and promotes the staff and patients' satisfaction.

Keywords: chemotherapy patients scheduling, integer programming, integrated scheduling, staff balancing

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Authors: Germans Natuhwera, Peter Ellis, Acuda Wilson, Anne Merriman, Martha Rabwoni

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Objective: The aim of the study was to diagnose the socio-economic burden and impact of a diagnosis of cervical cancer (CC) in rural women in the context of low-resourced country Uganda, using a phenomenological enquiry. Methods: This was a multi-site phenomenological inquiry, conducted at three hospice settings; Mobile Hospice Mbarara in southwestern, Little Hospice Hoima in Western, and Hospice Africa Uganda Kampala in central Uganda. A purposive sample of women with a histologically confirmed diagnosis of CC was recruited. Data was collected using open-ended audio-recorded interviews conducted in the native languages of participants. Interviews were transcribed verbatim in English, and Braun and Clarke’s (2019) framework of thematic analysis was used. Results: 13 women with a mean age of 49.2 and age range 29-71 participated in the study. All participants were of low socioeconomic status. The majority (84.6%) had advanced disease at diagnosis. A fuller reading of transcripts produced four major themes clustered under; (1) socioeconomic characteristics of women, (2) impact of CC on women’s relationships, (3) disrupted and impaired activities of daily living (ADLs), and (4) economic disruptions. Conclusions: A diagnosis of CC introduces significant socio-economic disruptions in a woman’s and her family’s life. CC causes disability, impairs the woman and her family’s productivity hence exacerbating levels of poverty in the home. High and expensive out-of-pocket expenditure on treatment, investigations, and transport costs further compound the socio-economic burden. Decentralizing cancer care services to regional centers, scaling up screening services, subsidizing costs of cancer care services, or making cervical cancer care treatment free of charge, strengthening monitoring mechanisms in public facilities to curb the vice of healthcare workers soliciting bribes from patients, increased mass awareness campaigns about cancer, training more healthcare professionals in cancer investigation and management, and palliative care, and introducing an introductory course on gynecologic cancers into all health training institutions are recommended.

Keywords: activities of daily living, cervical cancer, out-of-pocket, expenditure, phenomenology, socioeconomic

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Authors: Rubai M. Ochieng

Abstract:

Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

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Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

Abstract:

Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: Benhouda Afaf, Yahia Massinissa, Paolo Grieco

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Hyoscyamus albus L. is a small genus from Solanaceae family known by its use in old traditional medicine in the east of Algeria. Aim: This study aimed to characterize bioactive molecules from H. albus, evaluate their anticancer activity in several cancer cells and investigate their possible molecular mechanism. Materials and Methods: Different compounds (Peak h of fraction F), (Peak 3 of Fraction F), (Peak 1 of fraction C) were isolated from H.albus L by using high-performance chromatography (HPLC), mass spectrometry (MS) and proton NMR (NMR H1). All isolated compounds were subjected to cytotoxicity and antiproliferative assays against a panel of the four cell lines: DU-145, U-2 OS, U-87 MG and LN-229 cell lines and were determined using MTT assay, Annexin V and propodium iodide were used to evaluate apoptosis. Results: The phytochemical study of H. albus Fractions led to the isolation of quercetin-3-O-β-dglucopyranosyl-( 1 → 6)-β-d-glucopyranosid, N-trans-feruloyltyramine, Hydrocaffeoyl-N8- caffeoylspermidine.The biological results indicated that all cell lines were consistently sensitive to P1 FC in a dose-dependent manner. This difference in cytotoxic sensitivity was more pronounced in osteosarcoma cell line, U-2 OS, when compared to prostate cancer and U-87 MG. Cell viability data also demonstrated that only U-87 MG cells were responsive to treatment with Ph FF. compounds P1 FC and Ph FF have induced necrosis and apoptosis in a large part of LN-229 cells. Conclusion: The overall results of the present study provided evidence that isolated compounds are potential therapeutic entities against cancer.

Keywords: hyoscyamus albus, cancer cells, coumpounds, HPLC

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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