Search results for: cancer chemotherapy

Authors: Caren Hilger, Silke Burkert, Friederike Kendel

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Men with localized prostate cancer (PCa) have to choose among different treatment options, such as active surveillance (AS) and radical prostatectomy (RP). All available treatment options may be accompanied by specific psychological or physiological side effects. Depending on the nature and extent of these side effects, patients are more or less likely to be satisfied or to struggle with their treatment decision in the long term. Therefore, the aim of this study was to assess and explain decisional regret in men with localized PCa. The role of erectile functioning as one of the main physiological side effects of invasive PCa treatment, depressive symptoms as a common psychological side effect, and the association of erectile functioning and depressive symptoms with decisional regret were investigated. Men with localized PCa initially managed with AS or RP (N=292) were matched according to length of therapy (mean 47.9±15.4 months). Subjects completed mailed questionnaires assessing decisional regret, changes in erectile functioning, depressive symptoms, and sociodemographic variables. Clinical data were obtained from case report forms. Differences among the two treatment groups (AS and RP) were calculated using t-tests and χ²-tests, relationships of decisional regret with erectile functioning and depressive symptoms were computed using multiple regression. Men were on average 70±7.2 years old. The two treatment groups differed markedly regarding decisional regret (p<.001, d=.50), changes in erectile functioning (p<.001, d=1.2), and depressive symptoms (p=.01, d=.30), with men after RP reporting higher values, respectively. Regression analyses showed that after adjustment for age, tumor risk category, and changes in erectile functioning, depressive symptoms were still significantly associated with decisional regret (B=0.52, p<.001). Additionally, when predicting decisional regret, the interaction of changes in erectile functioning and depressive symptoms reached significance for men after RP (B=0.52, p<.001), but not for men under AS (B=-0.16, p=.14). With increased changes in erectile functioning, the association of depressive symptoms with decisional regret became stronger in men after RP. Decisional regret is a phenomenon more prominent in men after RP than in men under AS. Erectile functioning and depressive symptoms interact in their prediction of decisional regret. Screening and treating depressive symptoms might constitute a starting point for interventions aiming to reduce decisional regret in this target group.

Keywords: active surveillance, decisional regret, depressive symptoms, erectile functioning, prostate cancer, radical prostatectomy

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Authors: Mehrnaz Mostafavi

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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Laila Salah Seada, Ashraf Ibrahim, Fawaz Al Rashid, Ihab Abdo, Hassan Kasim, Waleed Al Mansi, Saud Al Shabli

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Background and Objectives: Colorectal carcinoma is increasing among both men and women worldwide. It has a multifactorial etiology including genetic factors, environmental factors and inflammatory conditions of the digestive tract. A clinicopathologic assessment of colorectal carcinoma in Hail region is done, considering any changing patterns in two 5-year periods from 2005-2009 (A) and from 2012 to 2017 (B). All data had been retrieved from histopathology files of King Khalid Hospital, Hail. Results: During period (A), 75 cases were diagnosed as colorectal carcinoma. Male patients comprised 56/75 (74.7%) of the study, with a mean age of 58.4 (36-97), while females were 19/75 (25.3%) with a mean age of 50.3(30-85) and the difference was significant (p = 0.05). M:F ratio was 2.9:1. Most common histological type was adenocarcioma in 68/75 (90.7%) patients mostly well differentiated in 44/68 (64.7%). Mucinous neoplasms comprised only 7/75 (9.3%) of cases and tended to have a higher stage (p = 0.04). During period (B), 115 cases were diagnosed with an increase of 53.3% in number of cases than period (A). Male to female ratio also decreased to 1.35:1, females being 44.83% more affected. Adenocarcinoma remained the prevalent type (93.9%), while mucinous type was still rare (5.2%). No distal metastases found at time of presentation. Localization of tumors was rectosigmoid in group (A) in 41.4%, which increased to 56.6% in group (B), with an increase of 15.2%. Iliocecal location also decreased from 8% to 3.5%, being 56.25% less. Other proximal areas of the colon were decreased by 25.75%, from 53.9% in group (A) to 40% in group (B). Conclusion: Colorectal carcinoma in Hail region has increased by 53.3% in the past 5 years, with more females being diagnosed. Localization has also shifted distally by 15.2%. These findings are different from Western world patterns which experienced a decrease in incidence and proximal shift of the colon cancer localization. This might be due to better diagnostic tools, population awareness of the disease, as well as changing of life style and/or food habits in the region.

Keywords: colorectal cancer, Hail Region, changing pattern, distal shift

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Authors: Noha E. Hassan

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Little is known regarding the influence of lymphatic microvessel density (LMVD) on prognosis in endometrial cancer. Prospective study was done in tertiary education and research hospital (Shatby Alexandria university hospital) on sixty patients presented with endometrial carcinoma underwent complete surgical staging. Our aim was to assess the intratumoral and peritumoral Lymphatic microvessel density (LMVD) of endometrial carcinomas identified by immunohistochemical staining using an antibody against podoplanin and to investigate their association with classical clinicopathological factors and prognosis. The result shows that high LMVD was associated with endometroid type of tumors, lesser myometrial, adnexal, cervical and peritoneal infiltration, lower tumor grade and stage and lesser recurrent cases. There is lower lymph node involvement among cases with high intratumoral LMVD and cases of high peritumoral LMVD; that reach statistical significance only among cases of high intratumoral LMVD. No association was seen between LMVD and lymphovascular space invasion. On the other hand, low LMVD was associated with poor outcome. Finally, we can conclude that increased LMVD is associated with favorable prognosis in endometrial cancer patients.

Keywords: endometrial carcinoma, lymphatic microvessel, microvessel density, prognosis

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Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

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Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

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Authors: Marzieh Ebrahimi, Vahid Changizi, Mohammad Reza Kardan, Seyed Mahdi Hosseini Pooya, Parham Geramifar

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Radiation exposure to the patient's family members is one of the major concerns during thyroid cancer radionuclide therapy. The aim of this study was to measure the total effective dose of the family members by means of thermoluminescence personal dosimeter, and compare with those calculated by analytical methods. Eighty-five adult family members of fifty-one patients volunteered to participate in this research study. Considering the minimum and maximum range of dose rate from 15 µsv/h to 120 µsv/h at patients' release time, the calculated mean and median dose values of family members were 0.45 mSv and 0.28 mSv, respectively. Moreover, almost all family members’ doses were measured to be less than the dose constraint of 5 mSv recommended by Basic Safety Standards. Considering the influence parameters such as patient dose rate and administrated activity, the total effective doses of family members were calculated by TEDE and NRC formulas and compared with those of experimental results. The results indicated that, it is fruitful to use the quantitative calculations for releasing patients treated with I-131 and correct estimation of patients' family doses.

Keywords: effective dose, thermoluminescence, I-131, thyroid cancer

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Szu-Mei Hsiao

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Many nurses have concerns about the difficulties of providing spiritual care for ethnic-Chinese patients and family members within their cultural context. This is due to a lack of knowledge and training. Most family caregivers are female. There has been little research exploring the potential impact of Chinese cultural values on the spiritual distress of couple dyadic participants in Taiwan. This study explores the spiritual issues of Taiwanese women coping with their husband’s advanced cancer during palliative care to death. Qualitative multiple case studies were used. Data was collected through participant observation and in-depth face-to-face interviews. Transcribed interview data was analyzed by using qualitative content analysis. Three couples were recruited from a community-based rural hospital in Taiwan where the husbands were hospitalized in a medical ward. Four spiritual distress themes emerged from the analysis: (1) A personal conflict in trying to come to terms with love and forgiveness; the inability to forgive their husband’s mistakes; and, lack of their family’s love and support. (2) A feeling of hopelessness due to advanced cancer, such as a feeling of disappointment in their destiny and karma, including expressing doubt on survival. (3) A feeling of uncertainty in facing death peacefully, such as fear of facing the unknown world; and, (4) A feeling of doubt causing them to question the meaning and values in their lives. This research has shown that caregivers needed family support, friends, social welfare, and the help of their religion to meet their spiritual needs in coping within the final stages of life and death. The findings of this study could assist health professionals to detect the spiritual distress of ethnic-Chinese patients and caregivers in the context of their cultural or religious background as early as possible.

Keywords: advanced cancer, Buddhism, Confucianism, Taoism, qualitative research, spiritual distress

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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Authors: Malak Shawky Matter Elyas

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Introduction: Early detection of breast cancer is the main tool to decrease morbidity and mortality rates. Many diagnostic tools are used, such as mammograms, ultrasound and magnetic resonance imaging, but none of them is conclusive, especially in very small sizes, less than 1 cm. So, there is a need for more accurate tools. Patients and methods: This study involved 13 patients with different breast lesions. 6 Patients had breast cancer, and one of them had metastatic axillary lymph nodes without clinically nor mammographically detected breast mass proved by biopsy and histopathology. Of the other 7 Patients, 4 of them had benign breast lesions proved by biopsy and histopathology, and 3 Patients showed Equivocal breast lesions on a mammogram. A volume of 370-444Mbq of (99m) Tc/ bombesin was injected. Dynamic 1-min images by Gamma Camera were taken for 20 minutes immediately after injection in the anterior view. Thereafter, two static images in anterior and prone lateral views by Gamma Camera were taken for 5 minutes. Finally, single-photon emission computed tomography images were taken for each patient. The definitive diagnosis was based on biopsy and histopathology. Results: 6 Patients with breast cancer proved by biopsy and histopathology showed Positive findings on Sestamibi (Scintimammography). 1 out of 4 Patients with benign breast lesions proved by biopsy and histopathology showed Positive findings on Sestamibi (Scintimammography) while the other 3 Patients showed Negative findings on Sestamibi. 3 Patients out of 3 Patients with equivocal breast findings on mammogram showed Positive Findings on Sestamibi (Scintimammography) and proved by biopsy and histopathology. Conclusions: While we agree that Scintimammography will not replace mammograms as a mass screening tool, we believe that many patients will benefit from Scintimammography, especially women with dense breast tissues and in the presence of breast implants that are difficult to diagnose by mammogram, wherein its sensitivity is low and in women with metastatic axillary lymph nodes without clinically nor mammographically findings. We can use Scintimammography in sentinel lymph node mapping as a more accurate tool, especially since it is non-invasive.

Keywords: breast., radiodiagnosis, lifestyle, surgery

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Authors: Angelis P. Barlampas

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Purpose or Learning Objective It is well known that previous examinations play a major role in futural diagnosis, thus avoiding unnecessary new exams that cost in time and money both for the patient and the health system. A case is presented in which past patient’s results, in combination with the least needed new tests, give an easy final diagnosis. Methods or Background A middle aged man visited the emergency department complaining of hard controlled, persisting fever for the last few days. Laboratory tests showed an elevated number of white blood cells with neutrophil shift and abnormal CRP. The patient was admitted to hospital a month ago for continuing lungs symptomatology after a recent covid-19 infection. Results or Findings Computed tomography scanning showed a solid mass with spiculating margins in right lower lobe. After intravenous iodine contrast administration, there was mildly peripheral enhancement and eccentric non enhancing area. A pneumonic cancer was suspected. Comparison with the patient’s latest computed tomography revealed no mass in the area of interest but only signs of recent post covid-19 lung parenchyma abnormalities. Any new mass that appears in a month’s time span can not be a cancer but a benign lesion. It was obvious that an abscess was the most suitable explanation. The patient was admitted to hospital, and antibiotic therapy was given, with very good results. After a few days, the patient was afebrile and in good condition. Conclusion In this case , a PET scan or a biopsy was avoided, thanks to the patient’s medical history and the availability of previous examinations. It is worthy encouraging the patients to keep their medical records and organizing more efficiently the health system with the current technology of archiving the medical examinations, too.

Keywords: covid-19, chest ct, cancer, abscess, fever

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Authors: M. Reza Roshandel, Tannaz Aghaei Badr, Batoul Khoundabi, Sara C. Lewis, Soroush Rais-Bahrami, John Sfakianos, Reza Mehrazin, Ash K. Tewari

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Introduction: Prostate biopsy is the most reliable diagnostic method for choosing the appropriate management of prostate cancer. However, discrepancies between Gleason grade groups (GG) of different biopsies remain a significant concern. This study aims to assess the association of the radiological factors with GG discrepancies in patients with index Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, using radical prostatectomy (RP) specimens as the most accurate and informative pathology. Methods: This single-institutional retrospective study was performed on a total of 2289 consecutive prostate cancer patients with combined targeted and systematic prostate biopsy followed by radical prostatectomy (RP). The database was explored for patients with the index PI-RADS 3 lesions version 2 and 2.1. Cancers with PI-RADS 4 or 5 scoring were excluded from the study. Patient characteristics and radiologic features were analyzed by multivariable logistic regression. Number-density of lesions was defined as the number of lesions per prostatic volume. Results: Of the 151 prostate cancer cases with PI-RADS 3 index lesions, 27% and 17% had upgrades and downgrades at RP, respectively. Analysis of grade changes showed no significant associations between discrepancies and the number or the number density of PI-RADS 3 lesions. Moreover, the study showed no significant association of the GG changes with race, age, location of the lesions, or prostate volume. Conclusions: This study demonstrated that in PI-RADS 3 cancerous nodules, the chance of the pathology changes in the final pathology of RP specimens was low. Furthermore, having multiple PI-RADS 3 nodules did not change the conclusion, as the possibility of grade changes in patients with multiple nodules was similar to those with solitary lesions.

Keywords: prostate, adenocarcinoma, multiparametric MRI, Gleason score, robot-assisted surgery

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Authors: Sunil Kumar

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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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Authors: Sandra Adarve, Jhon Osorio

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Uncertainty has been studied in patients with different types of cancer, except in patients with hematologic cancer and undergoing transplantation. The purpose of this study was to identify factors associated with uncertainty in adults patients with malignant hemato-oncology diseases who are scheduled to undergo hematopoietic stem cell transplantation based on Merle Mishel´s Uncertainty theory. This was a cross-sectional study with an analytical purpose. The study sample included 50 patients with leukemia, myeloma, and lymphoma selected by non-probability sampling by convenience and intention. Sociodemographic and clinical variables were measured. Mishel´s Scale of Uncertainty in Illness was used for the measurement of uncertainty. A bivariate and multivariate analyses were performed to explore the relationships and associations between the different variables and uncertainty level. For this analysis, the distribution of the uncertainty scale values was evaluated through the Shapiro-Wilk normality test to identify statistical tests to be used. A multivariate analysis was conducted through a logistic regression using step-by-step technique. Patients were 18-74 years old, with a mean age of 44.8. Over time, the disease course had a median of 9.5 months, an opportunity was found in the performance of the transplantation of < 20 days for 50% of the patients. Regarding the uncertainty scale, a mean score of 95.46 was identified. When the dimensions of the scale were analyzed, the mean score of the framework of stimuli was 25.6, of cognitive ability was 47.4 and structure providers was 22.8. Age was identified to correlate with the total uncertainty score (p=0.012). Additionally, a statistically significant difference was evidenced between different religious creeds and uncertainty score (p=0.023), education level (p=0.012), family history of cancer (p=0.001), the presence of comorbidities (p=0.023) and previous radiotherapy treatment (p=0.022). After performing logistic regression, previous radiotherapy treatment (OR=0.04 IC95% (0.004-0.48)) and family history of cancer (OR=30.7 IC95% (2.7-349)) were found to be factors associated with the high level of uncertainty. Uncertainty is present in high levels in patients who are going to be subjected to bone marrow transplantation, and it is the responsibility of the nurse to assess the levels of uncertainty and the presence of factors that may contribute to their presence. Once it has been valued, the uncertainty must be intervened from the identified associated factors, especially all those that have to do with the cognitive capacity. This implies the implementation and design of intervention strategies to improve the knowledge related to the disease and the therapeutic procedures to which the patients will be subjected. All interventions should favor the adaptation of these patients to their current experience and contribute to seeing uncertainty as an opportunity for growth and transcendence.

Keywords: hematopoietic stem cell transplantation, hematologic diseases, nursing, uncertainty

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Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

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BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

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Authors: Ademola Azeez

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Background: This study is a two year review of requests pattern for Prostate Specific Antigen (PSA), in a Nigerian tertiary health care institution. Prostate specific antigen was first described about 44 years ago but is still in use today for, diagnosis, monitoring, screening and prognosis of prostatic carcinoma though not-very specific as was widely believed. Prostate cancer is an increasingly important public health problem among adult men worldwide. Nigeria, which was formerly regarded as a low-incidence area by several authors is now witnessing a steep rise in the occurrence of this disease. This has been suggested to be due to increasing availability of screening tests and diagnostic facilities and not necessarily because of increased incidence of the diseases. Many notable Nigerians have died due to this dreaded disease. Methods: All plasma samples for PSA from January 2021-December 2022 were analyzed weekly by abbot autoanalyser, chemiluminescence assay method. Bio-data from request form were collated and analyzed. A total of 385 requests were received for the period under review. Result: There was an increase of request from inception to the last year of review. Smoked food, consumption of local herb and alcohol in order of importance, respectively, appears to be prominent factor in patient requested for PSA. The mean age was 67.years; the youngest was 29, while the oldest was 93years. Age 70 has the highest frequency of 8.5% .Mean PSA was 12.9ng/ml. There was a positive correlation between age and PSA (R=0.255, P < 0.05).Significant increase in PSA with age were reported. Men who retired from active jobs constitute the highest request for PSA test. Conclusion: There was an increasing trend in the proportion of requests with values outside the reference interval especially in patients diagnosed of benign prostatic hyperplasia, prostate cancer, while some routine test for PSA were elevated for the first time .This is in line with earlier report of increasing incidence of prostate cancer in Nigeria despite the increasing knowledge of healthy lifestyle.

Keywords: pattern, PSA, tertiary institution, Nigeria

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Authors: Hailemeleak Regassa

Abstract:

Traditional medicines use medicinal plants as a source of ingredients, and many modern medications are indirectly derived from plants. Consumers in affluent nations are growing disenchanted with contemporary healthcare and looking for alternatives. Oxidative stress is the primary cause of multiple diseases, and exogenous antioxidant supplementation or strengthening the body's endogenous antioxidant defenses are potential ways to counteract the negative effects of oxidative damage. Plants can biosynthesize non-enzymatic antioxidants that can reduce ROS-induced oxidative damage. Aging often aids the propagation and development of carcinogenesis, and older animals and older people exhibit increased vulnerability to tumor promoters. Cancer is a major public health issue, with several anti-cancer medications in clinical use. Potential drugs such as flavopiridol, roscovitine, combretastatin A-4, betulinic acid, and silvestrol are in the clinical or preclinical stages of research. Methodology: Microbial Growth media, Dimethyl sulfoxide (DMSO), methanol, ethyl acetate, and n-hexane were obtained from Himedia Labs, Mumbai, India. plant were collected from the Herbal Garden of Shoolini University campus, Solan, India (Latitude - 30.8644° N and longitude - 77.1184° E). The identity was confirmed by Dr. Y.S. Parmar University of Horticulture and Forestry, Nauni, Solan (H.P.), India, and documented in Voucher specimens - UHF- Herbarium no. 13784; vide book no. 3818 Receipt No. 086. The plant materials were washed with tap water, and 0.1% mercury chloride for 2 minutes, rinsed with distilled water, air dried, and kept in a hot air oven at 40ºc on blotting paper until all the water evaporated and became well dried for grinding. After drying, the plant materials were grounded using a mixer grinder into fine powder transferred into airtight containers with proper labeling, and stored at 4ºc for future use (Horablaga et al., 2023). The extraction process was done according to Altemimi et al., 2017. The 5g powder was mixed with 15 ml of the respective solvents (n-hexane, ethyl acetate, and methanol), and kept for 4-5 days on the platform shaker. The solvents used are based on their increasing polarity index. Then the extract was centrifuged at 10,000rpm for 5 minutes and filtered using No.1 Whatman filter paper.

Keywords: cancer, phytomedicine, medicinal plants, oncology

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Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

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Authors: Chien Y. Lin, Jung Y. Huang, Leu-Wei Lo

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A growing body of data reveals that the membrane cholesterol molecules can alter the signaling pathways of living cells. However, the understanding about how membrane cholesterol modulates receptor proteins is still lacking. Single-molecule tracking can effectively probe into the microscopic environments and thermal fluctuations of receptor proteins in a living cell. In this study we applies single-molecule optical tracking on ligand-induced dimerization process of EGFRs in the plasma membranes of two cancer cell lines (HeLa and A431) and one normal endothelial cell line (MCF12A). We tracked individual EGFR and dual receptors, diffusing in a correlated manner in the plasma membranes of live cells. We developed an energetic model by integrating the generalized Langevin equation with the Cahn-Hilliard equation to help extracting important information from single-molecule trajectories. From the study, we discovered that ligand-bound EGFRs move from non-raft areas into lipid raft domains. This ligand-induced motion is a common behavior in both cancer and normal cells. By manipulating the total amount of membrane cholesterol with methyl-β-cyclodextrin and the local concentration of membrane cholesterol with nystatin, we further found that the amount of cholesterol can affect the stability of EGFR dimers. The EGFR dimers in the plasma membrane of normal cells are more sensitive to the local concentration changes of cholesterol than EGFR dimers in the cancer cells. Our method successfully captures dynamic interactions of receptors at the single-molecule level and provides insight into the functional architecture of both the diffusing EGFR molecules and their local cellular environment.

Keywords: membrane proteins, single-molecule tracking, Cahn-Hilliard equation, EGFR dimers

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Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah

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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: Saba Ebrahimi, Saeed Ahmadian, Hedie Ashrafi

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Selecting appropriate patients for surgery is one of the main issues in thoracic surgery (TS). Both short-term and long-term risks and benefits of surgery must be considered in the patient selection criteria. There are some limitations in the existing datasets of TS patients because of missing values of attributes and imbalanced distribution of survival classes. In this study, a novel ensemble architecture of deep learning networks is proposed based on stacking different linear and non-linear layers to deal with imbalance datasets. The categorical and numerical features are split using different layers with ability to shrink the unnecessary features. Then, after extracting the insight from the raw features, a novel biased-kernel layer is applied to reinforce the gradient of the minority class and cause the network to be trained better comparing the current methods. Finally, the performance and advantages of our proposed model over the existing models are examined for predicting patient survival after thoracic surgery using a real-life clinical data for lung cancer patients.

Keywords: deep learning, ensemble models, imbalanced classification, lung cancer, TS patient selection

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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Authors: Chen Wang, Chun Liang

Abstract:

Microsatellite instability (MSI) is characterized by high degree of polymorphism in microsatellite (MS) length due to a deficiency in mismatch repair (MMR) system. MSI is associated with several tumor types and its status can be considered as an important indicator for tumor prognostic. Conventional clinical diagnosis of MSI examines PCR products of a panel of MS markers using electrophoresis (MSI-PCR) which is laborious, time consuming, and less reliable. MSIpred, a python 2 package for automatic classification of MSI was released by this study. It computes important somatic mutation features from files in mutation annotation format (MAF) generated from paired tumor-normal exome sequencing data, subsequently using these to predict tumor MSI status with a support vector machine (SVM) classifier trained by MAF files of 1074 tumors belonging to four types. Evaluation of MSIpred on an independent 358-tumor test set achieved overall accuracy of over 98% and area under receiver operating characteristic (ROC) curve of 0.967. These results indicated that MSIpred is a robust pan-cancer MSI classification tool and can serve as a complementary diagnostic to MSI-PCR in MSI diagnosis.

Keywords: microsatellite instability, pan-cancer classification, somatic mutation, support vector machine

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Authors: Ting-I Lin

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Objective: This article explores the nursing care experience of a 51-year-old terminal lung cancer patient admitted to the intensive care unit (ICU) following an upper right lobectomy. The patient initially sought emergency treatment due to worsening cough and dyspnea, which led to the placement of an endotracheal tube following sudden deterioration. Subsequent CT scans and chest X-rays revealed a tumor in the upper right lung with metastases to the lungs, liver, bones, and adrenal glands. The patient underwent a right upper lobectomy and a wedge resection of the right middle lobe. Pathology staging: T4N3M1c and the patient was diagnosed with advanced cancer postoperatively. Method: During the care period, nursing staff continuously monitored the patient’s physiological data through observations, direct care, interviews, physical assessments, and review of the patient’s medical records. The nursing team collaborated with the critical care team and the palliative care team, using Gordon's Eleven Functional Health Patterns to conduct a comprehensive assessment. The key health problems identified included pain related to postoperative cancer resection and invasive devices, fear of death due to rapid disease progression, and altered tissue perfusion associated with hemodynamic instability. Results: Postoperatively, the patient experienced pain from the surgical wound and dyspnea due to extensive metastasis, often leading to confusion. Through the adjustment of pain medication, the patient’s discomfort was alleviated, using Morphine 8 mg in 0.9% normal saline 60 ml IV drip q6h prn, and Ultracet 37.5 mg/325 mg 1# PO q6h. Additionally, lavender essential oil inhalation and limb massage were provided for 15 minutes four times a day. The patient’s FLACC pain score decreased from 7 to below 3. After respiratory training, the endotracheal tube was successfully removed, and the patient was weaned off the ventilator. Triflow exercises were used to promote alveolar expansion, with the goal of achieving 2 balls for 10 seconds, 5 repetitions per session, 6-8 times a day. The patient’s breathing stabilized at 16-18 breaths per minute, body temperature remained between 35.8°C and 36.1°C, and the mean arterial pressure was maintained between 60-80 mmHg. Conclusion: The critical care team and the palliative care team held a family meeting to discuss not only the patient’s care but also the emotional well-being of the family. Visiting hours were increased to two times per day, one hour each time, allowing the patient and family to express love and gratitude, which strengthened their emotional connection and reduced the patient’s anxiety from severe to mild. The family expressed that they had no regrets. After the patient was transferred to the general ward, the nursing team continued to provide end-of-life care with genuine empathy, compassion, and religious support, helping both the patient and family through the final stage of life.

Keywords: multiple metastases, lung cancer, palliative care, nursing experience

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