Search results for: consolidative chemotherapy

Authors: Angel Champion

Abstract:

Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

Procedia PDF Downloads 74

Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

Abstract:

Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

Procedia PDF Downloads 66

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

Procedia PDF Downloads 129

Authors: Cassandra Springate, Alexandra Furber, Jack E. Hines

Abstract:

Objectives: To create an evidence map of the cost-utility studies available with non-small cell lung cancer patients, and identify the geographical settings and interventions used. Methods: Using the Disease, Study Type, and Model Type filters in heoro.com we identified all cost-utility studies published between 1960 and 2017 with patients with non-small cell lung cancer. These papers were then indexed according to pre-specified categories. Results: Heoro.com identified 89 independent publications, published between 1995 and 2017. Of the 89 papers, 74 were published since 2010, 28 were from the USA, and 35 were from Europe, 16 of which were from the UK. Other publications were from China and Japan (13), Canada (9), Australia and New Zealand (4), and other countries (8). Fifty-nine studies included a chemotherapy intervention, of which 23 included erlotinib or gefitinib, 21 included pemetrexed or docetaxel, others included nivolumab (3), pembrolizumab (2), crizotinib (2), denosumab (2), necitumumab (1), and bevacizumab (1). Also, 19 studies modeled screening, staging, or surveillance strategies. Conclusions: The cost-utility studies found for NSCLC most commonly looked at the effectiveness of different chemotherapy treatments, with some also evaluating the addition of screening strategies. Most were also conducted with patient data from the USA and Europe.

Keywords: cancer, cost-utility, economic model, non-small cell lung cancer

Procedia PDF Downloads 150

Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

Abstract:

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

Procedia PDF Downloads 166

Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

Abstract:

The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

Procedia PDF Downloads 103

Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

Abstract:

Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

Procedia PDF Downloads 308

Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

Abstract:

Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

Procedia PDF Downloads 88

Authors: Nehir Nebioglu

Abstract:

Chemotherapy is widely used for the treatment of cancer. Doxorubicin is an anti-cancer chemotherapy drug that is classified as an anthracycline antibiotic. Antitumor antibiotics consist of natural products produced by species of the soil fungus Streptomyces. These drugs act in multiple phases of the cell cycle and are known cell-cycle specific. Although DOX is a precious clinical antineoplastic agent, resistance is also a problem that limits its utility besides cardiotoxicity problem. The drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. The mechanism of resistance is thought to involve, in particular, ABCB1 (MDR1, Pgp) and ABCC1 (MRP1) as well as other transporters. Several studies on DOX-resistant cell lines have shown that resistance can be overcome by an inhibition of ABCB1, ABCC1, and ABCC2. This study attempts to understand the effects of different concentration levels of glucose treatment and starvation on the proliferation of Doxorubicin resistant cancer cells lines. To understand the effect of starvation, K562/Dox and K562 cell lines were treated with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM Dox concentrations in both starvation and normal medium conditions. In addition to this, to interpret the effect of glucose treatment, different concentrations (0, 1 mM, 5 mM, 25 mM) of glucose were applied to Dox-treated (with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM) K562/Dox and K652 cell lines. All results show significant decreasing in the cell count of K562/Dox, when cells were starved. However, while proliferation of K562/Dox lines decrease is associated with the increasingly applied Dox concentration, K562/Dox starved ones remain at the same proliferation level. Thus, the results imply that an amount of K562/Dox lines gain starvation resistance and remain resistant. Furthermore, for K562/Dox, there is no clear effect of glucose treatment in terms of cell proliferation. In the presence of a moderate level of glucose (5 mM), proliferation increases compared to other concentration of glucose for each different Dox application. On the other hand, a significant increase in cell proliferation in moderate level of glucose is only observed in 5 uM Dox concentration. The moderate concentration level of Dox can be examined in further studies. For the high amount of glucose (25 mM), cell proliferation levels are lower than moderate glucose application. The reason could be high amount of glucose may not be absorbable by cells. Also, in the presence of low amount of glucose, proliferation is decreasing in an orderly manner of increase in Dox concentration. This situation can be explained by the glucose depletion -Warburg effect- in the literature.

Keywords: drug resistance, cancer cells, chemotherapy, doxorubicin

Procedia PDF Downloads 176

Authors: Jyoti Srivastava, Sandhya S. Kaushik, Mallika Tewari, Hari S. Shukla

Abstract:

Little information is available about the development of psychological well being over time among women who have been undergoing treatment for breast cancer. The aim of this study was to identify the trajectories of depression anxiety and stress among women with early-stage breast cancer. Of the 48 Indian women with newly diagnosed early-stage breast cancer recruited from surgical oncology unit, 39 completed an interview and were assessed for depression anxiety and stress (Depression Anxiety Stress Scale-DASS 21) before their first course of chemotherapy (baseline) and follow up interviews at 3, 6 and 9 months thereafter. Growth mixture modeling was used to identify distinct trajectories of Depression Anxiety and Stress symptoms. Logistic Regression analysis was used to evaluate the characteristics of women in distinct groups. Most women showed mild to moderate level of depression and anxiety (68%) while normal to mild level of stress (71%). But one in 11 women was chronically anxious (9%) and depressed (9%). Young age, having a partner, shorter education and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong nine months after diagnosis. By looking beyond the mean, it was found that several socio-demographic and treatment factors characterized the women whose depression, anxiety and stress level remained severe even nine months after diagnosis. The results suggest that support provided to cancer patients should have a special focus on a relatively small group of patient most in need.

Keywords: psychological well being, growth mixture modeling, logistic regression analysis, socio-demographic factors

Procedia PDF Downloads 147

Authors: Haile F. Darge, Hsieh C. Tsai

Abstract:

The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

Procedia PDF Downloads 134

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

Procedia PDF Downloads 274

Authors: S. Sakhri

Abstract:

Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

Procedia PDF Downloads 209

Authors: Jie Gao

Abstract:

The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

Procedia PDF Downloads 420

Authors: Rizwan Iqbal

Abstract:

Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

Procedia PDF Downloads 62

Authors: Sara Malik, Andreea. S. Calude, Joseph Ulatowski

Abstract:

This paper explores how speakers from New Zealand and Pakistan with breast cancer use violence metaphors to communicate the intensity of their experiences during various stages of illness. With the theoretical foundation in Conceptual Metaphor Theory and the use of Metaphor Identification Procedure for metaphor analysis, this study investigates how speakers with breast cancer use violence metaphors in different cultural contexts. it collected a corpus of forty-six personal narratives from New Zealand and thirty-six from Pakistan, posted between 2011 and 2023 on YouTube by breast cancer organisations, such as ‘NZ Breast Cancer Foundation’ and ‘Pink Ribbon Pakistan’. The data was transcribed using the Whisper AI tool and then curated to include only patients’ discourse, further organised into eight narrative topics: testing phase, treatment phase, remission phase, family support, campaigns and awareness efforts, government support and funding, general information and religious discourse. In this talk, it discuss two aspects of the use of violence metaphors, a) differences in the use of violence metaphors across various narrative topics, and b) lexical variations in the choice of such metaphors. The findings suggest that violence metaphors were used differently across various stages of illness experience. For instance, during the ‘testing phase,’ violence metaphors were employed to convey a sense of punishment as reflected in statements like, ‘Feeling like it was a death sentence, an immediate death sentence’ (NZ Example) and ‘Jese hi aap ko na breast cancer ka pata chalta hai logon ko yeh hona shuru ho jata hai ke oh bas ab to moat ka parwana mil gaya hai’ (Because as soon as you find out you have breast cancer people start to feel that you have received a death warrant) (PK Example). On the other hand, violence metaphor during the ‘treatment phase’ highlighted negative experiences related to chemotherapy as seen in statements like ‘The first lot of chemo I had was disastrous’ (NZ Example) and ‘...chemotherapy ke to, it's the worst of all, it's like a healing poison’ (chemotherapy, it's the worst of all, it's like a healing poison) (PK Example). Second, lexical variations revealed how ‘sunburn’ (a common phenomenon in the NZ) was used as a metaphor to describe the effects of radiotherapy, whereas in the discourse from Pakistan, a more general term, 'burn,' was used instead. In this talk, we will explore the possible reasons behind the different word choices made by speakers from both countries to describe the same process. This study contributes to understanding the use of violence metaphors across various narrative topics of the illness experience and explains how and why speakers from two different countries use lexical variations to describe the same process.

Keywords: metaphors, breast cancer discourse, cognitive linguistics, lexical variations, New zealand english, pakistani urdu

Procedia PDF Downloads 31

Authors: Sayed Ali Garossi, Azar Heidarizadi, Shahla Mohammad Ganji

Abstract:

Context: Colorectal cancer is the second type of cancer-related mortality globally. Expression of cas8 (caspase 8) is closely connected to growth and metastasis of colorectal cancer.Cas8/Rip1 plays a vital role in the apoptosis pathway and resistance to chemotherapy. The aim of the present study is to investigate the pattern of gene expression in colorectal cancer and compare the differences using Real-Time PCR to find a potential biomarker candidate for colorectal cancer. Methodology: This study conducted real-time PCR to evaluate gene expression of Cas8 in colorectal cancer patients. The gene-specific primer sequences exon–exon junction was designed by OLIGO7 software for the expression of the gene under investigation. Forty-six patient samples without any chemotherapy were selected, including tumoral tissue and adjacent normal tissue samples. The age of the patients was 50 and the size of the tumors was 5.5 cm. The categories were before and after age 50. Findings: Here, we found that Caspase 8 was overexpressed in CRC tissues compared to corresponding adjacent colon tissues (Cas8: 5.2 vs. 1 ratio); high expression of Cas8 was associated with poor overall survival and independent risk factors for the prognosis of CRC patients. Conclusion: In conclusion, our study pioneered the reporting of high Casp8 expression as a predictor of poor prognosis and chemical resistance in CRC patients.Cas8 overexpression suppressed Cas 8 / Rip1-dependent apoptosis and activated the proliferation of tumor cells by activating necroptosis. The necroptosis pathway has also emerged as a new approach to anti-tumor in cancer treatment.

Keywords: Cas8, necroptosis, apoptosis, Real-Time PCR

Procedia PDF Downloads 55

Authors: P. Hooshangitabrizi, I. Contreras, N. Bhuiyan

Abstract:

This work presents an online scheduling problem which accommodates multiple requests of patients for chemotherapy treatments in a cancer center of a major metropolitan hospital in Canada. To solve the problem, an adaptive flexible approach is proposed which systematically combines two optimization models. The first model is intended to dynamically schedule arriving requests in the form of waiting lists whereas the second model is used to reschedule the already booked patients with the goal of finding better resource allocations when new information becomes available. Both models are created as mixed integer programming formulations. Various controllable and flexible parameters such as deviating the prescribed target dates by a pre-determined threshold, changing the start time of already booked appointments and the maximum number of appointments to move in the schedule are included in the proposed approach to have sufficient degrees of flexibility in handling arrival requests and unexpected changes. Several computational experiments are conducted to evaluate the performance of the proposed approach using historical data provided by the oncology clinic. Our approach achieves outstandingly better results as compared to those of the scheduling system being used in practice. Moreover, several analyses are conducted to evaluate the effect of considering different levels of flexibility on the obtained results and to assess the performance of the proposed approach in dealing with last-minute changes. We strongly believe that the proposed flexible adaptive approach is very well-suited for implementation at the clinic to provide better patient-care services and to utilize available resource more efficiently.

Keywords: chemotherapy scheduling, multi-appointment modeling, optimization of resources, satisfaction of patients, mixed integer programming

Procedia PDF Downloads 167

Authors: Chamilani Nikapitiya, Mahanama De Zoysa, Jehee Lee

Abstract:

Most of the bacterial diseases are associated with high mortalities in aquaculture species and causing huge economic losses. Different approaches have been taken to prevent or control of bacterial diseases including use of vaccines, probiotics, chemotherapy, water quality management, etc. Antibiotics are widely applying as chemotherapy to control bacterial diseases, however, it has been shown that frequent use of antibiotics is favored to develop multi-drug resistance bacteria. Therefore, phages and phage encoded lytic proteins are known to be one of the most promising alternatives for antibiotics to avoid the emergence of antibiotic-resistant bacteria. We isolated and characterized the two lytic phages, namely pAh-1 and pAs-1 against pathogenic Aeromonas hydrophila and Aeromonas salmonicida, respectively. Morphological characteristics were analyzed by Transmission electron microscopy (TEM) and host strain specificities were tested with Aeromonas and other closely related bacterial strains. TEM analysis revealed that both pAh-1 and pAsm-1 are composed of an icosahedral head and a segmented tail, and we suggest that, they are new members of Myoviridae family. Genome sizes of isolated phages were estimated by restriction enzyme digestion of genomic DNA using selected endonucleases followed by agarose gel electrophoresis. Estimated genome size of pAh-1 and pAs-1 were approximately 64 Kbp and 120 Kbp, respectively. Both pAh-1 and pAs-1 have shown narrow host specificity. Moreover, protective effects of phage therapy against fish pathogenic A. hydrophila were investigated in zebrafish model. The survival rate was 40% higher when zebrafish received intra-peritoneal injection (i.p.) of pAh-1 were simultaneously challenge A. hydrophila (2 x 106 CFU/fish) compared to that without phage treatment. Overall results suggest that both pAh-1 and pAs-1 can be used as a potential phage therapy to control Aeromonas infections in aquaculture.

Keywords: Aeromonas infections, antibiotic resistance, bacteriophage, bio-control, lytic phage

Procedia PDF Downloads 193

Authors: Adrian Hang Yue Siu, Matthew Holyland, Sharon Carey, Daniel Steffens, Nabila Ansari, Cherry E. Koh

Abstract:

Introduction: Peritoneal malignancies are challenging cancers to manage. While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) may offer a cure, it’s considered radical and morbid. Pre-emptive identification of deconditioned patients for optimization may mitigate the risks of surgery. However, the difficulty lies in the scarcity of validated predictive tools to identify high-risk patients. In recent times, there has been growing interest in sarcopenia, which can occur as a result of malnutrition and malignancies. Therefore, the purpose of this study was to assess the utility of sarcopenia in predicting post-operative outcomes. Methods: A single quaternary-center retrospective study of CRS and HIPEC patients between 2017-2020 was conducted to determine the association between pre-operative sarcopenia and post-operative outcomes. Lumbar CT images were analyzed using Slice-o-matic® to measure sarcopenia. Results : Cohort (n=94) analysis found that 40% had sarcopenia, with a majority being female (53.2%) and a mean age of 55 years. Sarcopenia was statistically associated with decreased weight compared to non-sarcopenia patients, 72.7kg vs. 82.2kg (p=0.014) and shorter overall survival, 1.4 years vs. 2.1 years (p=0.032). Post-operatively, patients with sarcopenia experienced more post-operative complications (p=0.001). Conclusion: Complex procedures often require optimization to prevent complications and improve survival. While patient biomarkers – BMI and weight – are used for optimization, this research advocates for the identification of sarcopenia status for pre-operative planning. Sarcopenia may be an indicator of advanced disease requiring further treatment and is an emerging area of research. Larger studies are required to confirm these findings and to assess the reversibility of sarcopenia after surgery.

Keywords: sarcopaenia, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, surgical oncology

Procedia PDF Downloads 85

Authors: Shivayogi Charantimath

Abstract:

Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1^st and 2^nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1^st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1^st and 2^nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1^st week and 53.6% for 2^nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1^st week and 33.3% in 2^nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1^st week follow up and 0.000 for 2^nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

Procedia PDF Downloads 351

Authors: J. F. Pollo Gaspary, F. Peron Gaspary, E. M. Simão, R. Concatto Beltrame, G. Orengo de Oliveira, M. S. Ristow Ferreira, F. Sartori Thies, I. F. Minello, F. dos Santos de Oliveira

Abstract:

Background: The immune system has evolved several mechanisms to protect the host against cancer, and it has now been suggested that the expansion of its functions may prevent tumor growth and control the symptoms of cancer patients. Two techniques, ozone therapy and pulsed electromagnetic fields (PEMF), are independently associated with an increase in the immune system functions and they maybe help palliative care of patients in these conditions. Case Report: A patient with rectal adenocarcinoma with metastases decides to interrupt the clinical chemotherapy protocol due to refractoriness and side effects. As a palliative care alternative treatment it is suggested to the patient the use of ozone therapy associated with PEMF techniques. Results: The patient reports an improvement in well-being, in autonomy and in pain control. Imaging tests confirm a pause in tumor growth despite more than 60 days without using classic treatment. These results associated with palliative care alternative treatment stimulate the return to the chemotherapy protocol. Discussion: This case illustrates that these two techniques can contribute to the control of tumor growth and refractory symptoms, such as pain, probably by enhancing the immune system. Conclusions: The potential use of the combination of these two therapies, ozone therapy and PEMF therapy, can contribute to palliation of cancer patients, alone or in combination with pharmacological therapies. The conduct of future investigations on this paradigm can elucidate how much these techniques contribute to the survival and well-being of these patients.

Keywords: cancer, complementary and alternative medicine , ozone therapy, palliative care, PEMF therapy

Procedia PDF Downloads 155

Authors: Himanshu Rohela

Abstract:

BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

Procedia PDF Downloads 70

Authors: Mohammad Mohammadi, Mohammad Pashmchi

Abstract:

Background: Malnutrition commonly develops and worsens following gastric cancer surgery, particularly after discharge, which is associated with adverse outcomes. Former studies have primarily focused on patients during their hospital stay period, and there is limited evidence regarding the recommendation of nutritional interventions for patients after discharge from the hospital following gastric cancer surgery. This review is aimed to evaluate the efficiency of post-discharge dietary counseling with oral nutritional supplements (ONS), and dietary counseling alone on post-surgical nutritional outcomes in patients undergoing gastric cancer surgery. Methods: The four databases of Embase, PubMed, web of science, and google scholar were searched up to November 2022 for relevant randomized controlled trials. The Cochrane Collaboration’s assessment tool for randomized trials was used to evaluate the quality of studies. Results: Compared to patients who only received dietary counseling, patients who received both dietary counseling and ONS had considerably higher SMI, BMI, and less weight loss and sarcopenia occurrence rate. The patients who had received dietary counseling and ONS had significantly lower risk of chemotherapy intolerance. No differences in the readmission rate between the two groups was found. In terms of the quality of life, concomitant dietary advice and ONS significantly was associated with lower appetite loss and fatigue rate, but there was no difference in the other outcomes between the two groups. Conclusions: Post-discharge dietary advice with ONS following gastric cancer surgery may improve skeletal muscle maintenance, nutritional outcomes, quality of life variables, and chemotherapy tolerance. This evidence supports the recommendation of post-discharge dietary advice with ONS for patients who underwent gastric cancer surgery.

Keywords: gastric cancer surgery, oral nutritional supplements, malnutrition, gastric cancer

Procedia PDF Downloads 73

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

Procedia PDF Downloads 435

Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

Abstract:

Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

Procedia PDF Downloads 241

Authors: Omar Nouri, Wafa Mnejja, Fatma Dhouib, Syrine Zouari, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Leila Farhat, Nejla Fourati, Jamel Daoud

Abstract:

Purpose and Objective: Intensity modulated radiation (IMRT) technique, associated with induction chemotherapy (IC) and/or concomitant chemotherapy (CC), is actually the recommended treatment modality for nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the therapeutic results and the patterns of relapse with this treatment protocol. Material and methods: A retrospective monocentric study of 145 patients with NPC treated between June 2016 and July 2021. All patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. The high-risk volume dose was 66.5 Gy in children. Survival analysis was performed according to the Kaplan-Meier method, and the Log-rank test was used to compare factors that may influence survival. Results: Median age was 48 years (11-80) with a sex ratio of 2.9. One hundred-twenty tumors (82.7%) were classified as stages III-IV according to the 2017 UICC TNM classification. Ten patients (6.9%) were metastatic at diagnosis. One hundred-thirty-five patient (93.1%) received IC, 104 of which (77%) were TPF-based (taxanes, cisplatin and 5 fluoro-uracil). One hundred-thirty-eight patient (95.2%) received CC, mostly cisplatin in 134 cases (97%). After a median follow-up of 50 months [22-82], 46 patients (31.7%) had a relapse: 12 (8.2%) experienced local and/or regional relapse after a median of 18 months [6-43], 29 (20%) experienced distant relapse after a median of 9 months [2-24] and 5 patients (3.4%) had both. Thirty-five patients (24.1%) died, including 5 (3.4%) from a cause other than their cancer. Three-year overall survival (OS), cancer specific survival, disease free survival, metastasis free survival and loco-regional free survival were respectively 78.1%, 81.3%, 67.8%, 74.5% and 88.1%. Anatomo-clinic factors predicting OS were age > 50 years (88.7 vs. 70.5%; p=0.004), diabetes history (81.2 vs. 66.7%; p=0.027), UICC N classification (100 vs. 95 vs. 77.5 vs. 68.8% respectively for N0, N1, N2 and N3; p=0.008), the practice of a lymph node biopsy (84.2 vs. 57%; p=0.05), and UICC TNM stages III-IV (93.8 vs. 73.6% respectively for stage I-II vs. III-IV; p=0.044). Therapeutic factors predicting OS were a number of CC courses (less than 4 courses: 65.8 vs. 86%; p=0.03, less than 5 courses: 71.5 vs. 89%; p=0.041), a weight loss > 10% during treatment (84.1 vs. 60.9%; p=0.021) and a total cumulative cisplatin dose, including IC and CC, < 380 mg/m² (64.4 vs. 87.6%; p=0.003). Radiotherapy delay and total duration did not significantly affect OS. No grade 3-4 late side effects were noted in the evaluable 127 patients (87.6%). The most common toxicity was dry mouth which was grade 2 in 47 cases (37%) and grade 1 in 55 cases (43.3%).Conclusion: IMRT for nasopharyngeal carcinoma granted a high loco-regional control rate for patients during the last five years. However, distant relapses remain frequent and conditionate the prognosis. We identified many anatomo-clinic and therapeutic prognosis factors. Therefore, high-risk patients require a more aggressive therapeutic approach, such as radiotherapy dose escalation or adding adjuvant chemotherapy.

Keywords: therapeutic results, prognostic factors, intensity-modulated radiotherapy, nasopharyngeal carcinoma

Procedia PDF Downloads 64

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

Abstract:

Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

Procedia PDF Downloads 84

Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze

Abstract:

Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.

Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants

Procedia PDF Downloads 270

Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

Abstract:

Background and Significance: Breast cancer is the most frequently diagnosed and leading cause of cancer death among women. This study aims to determine factors potentially predicting recurrence and long-term survival after the first recurrence in surgically treated patients between postmenopausal and younger women. Methods and Analysis: A retrospective cohort study was performed on 498 Thai women with invasive breast cancer, who had undergone mastectomy and been followed-up at Ubon Ratchathani Cancer Hospital, Thailand. We collected based on a systematic chart audit from medical records and pathology reports between January 1, 2002, and December 31, 2011. The last follow-up time point for surviving patients was December 31, 2016. A Cox regression model was used to calculate hazard ratios of recurrence and death. Findings: The median age was 49 (SD ± 9.66) at the time of diagnosis, 47% was post-menopausal women ( ≥ 51years and not experienced any menstrual flow for a minimum of 12 months), and 53 % was younger women ( ˂ 51 years and have menstrual period). Median time from the diagnosis to the last follow-up or death was 10.81 [95% CI = 9.53-12.07] years in younger cases and 8.20 [95% CI = 6.57-9.82] years in postmenopausal cases. The recurrence-free survival (RFS) for younger estimates at 1, 5 and 10 years of 95.0 %, 64.0% and 58.93% respectively, appeared slightly better than the 92.7%, 58.1% and 53.1% for postmenopausal women [HRadj = 1.25, 95% CI = 0.95-1.64]. Regarding overall survival (OS) for younger at 1, 5 and 10 years were 97.7%, 72.7 % and 52.7% respectively, for postmenopausal patients, OS at 1, 5 and 10 years were 95.7%, 70.0% and 44.5 respectively, there were no significant differences in survival [HRadj = 1.23, 95% CI = 0.94 -1.64]. Multivariate analysis identified five risk factors for negatively impacting on survival were triple negative [HR= 2.76, 95% CI = 1.47-5.19], Her2-enriched [HR = 2.59, 95% CI = 1.37-4.91], luminal B [HR = 2.29, 95 % CI=1.35-3.89], not free margin [HR = 1.98, 95%CI=1.00-3.96] and patients who received only adjuvant chemotherapy [HR= 3.75, 95% CI = 2.00-7.04]. Statistically significant risks of overall cancer recurrence were Her2-enriched [HR = 5.20, 95% CI = 2.75-9.80], triple negative [HR = 3.87, 95% CI = 1.98-7.59], luminal B [HR= 2.59, 95% CI = 1.48-4.54,] and patients who received only adjuvant chemotherapy [HR= 2.59, 95% CI = 1.48-5.66]. Discussion and Implications: Outcomes from this studies have shown that postmenopausal women have been associated with increased risk of recurrence and mortality. As the results, it provides useful information for planning the screening and treatment of early-stage breast cancer in the future.

Keywords: breast cancer, menopause status, recurrence-free survival, overall survival

Procedia PDF Downloads 163