Search results for: cancer thernostics

Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Yong Seong Kim, Seongbin Hong, So Hun Kim, Moonsuk Nam

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Background: Patients who undergo thyroidectomy due to thyroid cancer often complain weight gain, although they are on suppressive thyroid hormone treatment. The aim of this study is to know whether thyroid cancer patients gain the weight after thyroidectomy and weight change is dependent on estrogen state or use of rhTSH. Material and Method: We performed a retrospective chart review of subjects receiving medical care at an academic medical center. Two hundred two patients who underwent total thyroidectomy were included. As a control group, patients with thyroid nodule and euthyroidism were matched for age, gender, menopausal status. The weight changes occurring over first one year and thyroid function were assessed. Results: Mean age was 51±12 years and patients was composed with 38% of premenopausal, 15 % perimenopausal women, 37% of postmenopausal women and 20% of men. Patients with thyroid cancer gained 2.2 kg during the first year. It’ was not significantly different with control. However, weigh change in perimenopausal and post menopausal women gained more weight than control (P <0.05). Age, baseline body weight and weight gain were not correlated. Discussion: Patient who had undergone thyroidectomy gained more weight than their control, especially in peri- and postmenopausal women. Patients in this age should be monitored for their weight carefully.

Keywords: weight gain, thyroidectomy, thyroid cancer, weight chance

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Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Shradha Parsekar, Suma Nair, Ajay Bailey, Binu V. S.

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Background: Concealing of cancer-related information is seen in many low-and-middle-income countries and may be associated with multiple factors. Comparatively, there is lack of information about, how breast cancers diagnosed women disclose cancer-related information to their social contacts and vice versa. To get more insights on the participant’s experience, opinions, expectations, and attitudes, a qualitative study is a suitable approach. Therefore, this study involving in-depth interviews was planned to lessen this gap. Methods: Interviews were conducted separately among breast cancer patients and their caregivers with semi-structured qualitative interview guide. Purposive and convenient sampling was being used to recruit patients and caregivers, respectively. Ethical clearance and permission from the tertiary hospital were obtained and participants were selected from the Udupi district, Karnataka, India. After obtaining a list of breast cancer diagnosed cases, participants were contacted in person and their willingness to take part in the study was taken. About 39 caregivers and 35 patients belonging to different breast cancer stages were recruited. Interviews were recorded with prior permission. Data was managed by Atlas.ti 8 software. The recordings were transcribed, translated and coded in two cycles. Most of the patients belonged to stage II and III cancer. Codes were grouped together into to whom breast cancer status was concealed to and underneath reason for the same. Main findings: followings are the codes and code families which emerged from the data. 1) Concealing the breast cancer status from social contacts other than close family members (such as extended family, neighbor and friends). Participants perceived the reasons as, a) to avoid questions which people probe (which doesn’t have answers), b) to avoid people paying courtesy visit (to inquire about the health as it is Indian culture to visit the sick person) making it inconvenient for patient and caregivers have to offer something and talk to them, c) to avoid people getting shocked (react as if cancer is different from other diseases) or getting emotional/sad, or getting fear of death d) to avoid getting negative suggestion or talking anything in front of patient as it may affect patient negatively, e) to avoid getting stigmatized, f) to avoid getting obstacle in child’s marriage. 2) Participant concealed the breast cancer status of young children as they perceived that it may a) affect studies, b) affect emotionally, c) children may get scared. 3) Concealing the breast cancer status from patients as the caregivers perceived that they have fear of a) worsening patient’s health, b) patient getting tensed, c) patient getting shocked, and d) patient getting scared. However, some participants stressed important in disclosing the cancer status to social contact/patient to make the people aware of the disease. Conclusion: The news of breast cancer spreads like electricity in the wire, therefore, patient or family avoid it for many reasons. Although, globally, due to physicians’ ethical obligations, there is an inclination towards more disclosure of cancer diagnosis and status of prognosis to the patient. However, it is an ongoing argument whether patient/social contacts should know the status especially in a country like India.

Keywords: breast cancer, concealing cancer status, India, qualitative study

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Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

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Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

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Authors: Martyn Queen, Diane Crone, Andrew Parker, Saul Bloxham

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Rationale: There is a growing body of evidence that supports the use of physical activity during and after cancer treatment. However, activity levels for patients remain low. As more cancer patients are treated successfully, and treatment costs continue to escalate, physical activity may be a promising adjunct to a person-centred healthcare approach to recovery. Aim: The aim was to further understand how physical activity may enhance the recovery process for a group of mixed-site cancer patients. Objectives: The research investigated longitudinal changes in physical activity and perceived the quality of life between two and six month’s post-exercise interventions. It also investigated support systems that enabled patients to sustain these perceived changes. Method: The respondent cohort comprised 14 mixed-site cancer patients aged 43-70 (11 women, 3 men), who participated in a two-phase physical activity intervention that took place at a university in the South West of England. Phase 1 consisted of an eight-week structured physical activity programme; Phase 2 consisted of four months of non-supervised physical activity. Semi-structured interviews took place three times over six months with each participant. Grounded theory informed the data collection and analysis which, in turn, facilitated theoretical development. Findings: Our findings propose three theories on the impact of physical activity for recovering cancer patients: 1) Knowledge gained through a structured exercise programme can enable recovering cancer patients to independently sustain physical activity to four-month follow-up. 2) Sustaining physical activity for six months promotes positive changes in the quality of life indicators of chronic fatigue, self-efficacy, the ability to self-manage and energy levels. 3) Peer support from patients facilitates adherence to a structured exercise programme and support from a spouse, or life partner facilitates independently sustained physical activity to four-month follow-up. Conclusions: This study demonstrates that qualitative research can provide an evidence base that could be used to support future care plans for cancer patients. Findings also demonstrate that a physical activity intervention can be effective at helping cancer patients recover from the side effects of their treatment, and recommends that physical activity should become an adjunct therapy alongside traditional cancer treatments.

Keywords: physical activity, health, cancer recovery, quality of life, support systems, qualitative, grounded theory, person-centred healthcare

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Authors: Po-Jung Huang, Chi-Ching Lee, Bertrand Chin-Ming Tan, Yuan-Ming Yeh, Julie Lichieh Chu, Tin-Wen Chen, Cheng-Yang Lee, Ruei-Chi Gan, Hsuan Liu, Petrus Tang

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Whole-exome sequencing focuses on the protein coding regions of disease/cancer associated genes based on a priori knowledge is the most cost-effective method to study the association between genetic alterations and disease. Recent advances in high throughput sequencing technologies and proteomic techniques has provided an opportunity to integrate genomics and proteomics, allowing readily detectable mutated peptides corresponding to mutated genes. Since sequence database search is the most widely used method for protein identification using Mass spectrometry (MS)-based proteomics technology, a mutant proteome database is required to better approximate the real protein pool to improve disease-associated mutated protein identification. Large-scale whole exome/genome sequencing studies were launched by National Cancer Institute (NCI), Broad Institute, and The Cancer Genome Atlas (TCGA), which provide not only a comprehensive report on the analysis of coding variants in diverse samples cell lines but a invaluable resource for extensive research community. No existing database is available for the collection of mutant protein sequences related to the identified variants in these studies. CMPD is designed to address this issue, serving as a bridge between genomic data and proteomic studies and focusing on protein sequence-altering variations originated from both germline and cancer-associated somatic variations.

Keywords: TCGA, cancer, mutant, proteome

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Authors: Sundaresan Sivapatham, B. Prabhu

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Cancer results from a multistage, multi-mechanism carcinogenesis process that involves mutagenic, cell death and epigenetic mechanisms, during the three distinguishable but closely allied stages: initiation, promotion, and progression. Chemoprevention is promising in the realm of cancer prevention and it has been shown to reduce the risk of development of carcinoma in highly susceptible individuals such as those with known genetic mutations or high level of risk factors. The present study is aimed at the need of early detection of bladder cancer in order to improve performance in the treatment of this disease. Consumption of certain natural products like DIM is associated with a reduction in cancer incidence in humans. The study showed the protective effects of Diindolylmethane in N-Butyl-N-(4-hydroxybutyl) nitrosamine treated rats. Results of the study had shown the changes in the tumor markers, biomarkers and histopathological alterations in experimental rats when compared to control rats. The protective effects of DIM were shown from the results of cell proliferation, apoptotic markers and histopathological findings when compared with experimental control animals. Hence, our results speculate that the tumor markers, apoptotic markers, histopathological changes and cell proliferation index measured as PCNA serves as an indicator suggestive of protective effects of DIM in BBN induced urinary bladder carcinogenesis.

Keywords: bladder cancer, N-Butyl-N-(4-hydroxybutyl) nitrosamine, diindolylmethane, histopathology

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Authors: Prathama Guha Chaudhuri, Arunima Datta, Ashis Mukhopadhyay

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Background: Visualization (guided imagery) is a set of techniques which induce relaxation and help people create positive mental images in order to reduce stress.It is relatively inexpensive and can even be practised by bed bound people. Studies have shown visualization to be an effective tool to improve cancer patients’ anxiety, depression and quality of life. The common images used with cancer patients in the developed world are those involving the individual’s body and its strengths. Since breast cancer patients in India are more family oriented and often their main concerns are the stigma of having cancer and subsequent isolation of their families, including their children, we figured that positive images involving acceptance and integration within family and society would be more effective for them. Method: Data was collected from 119 breast cancer patients on chemotherapy willing to undergo psychotherapy, with no history of past psychiatric illness. Their baseline stress, anxiety, depression and quality of life were assessed using validated tools. The participants were then randomly divided into three groups: a) those who received visualization therapy with standard imageries involving the body and its strengths (sVT), b) those who received visualization therapy using indigenous family oriented imageries (mVT) and c) a control group who received supportive therapy. There were six sessions spread over two months for each group. The psychological outcome variables were measured post intervention. Appropriate statistical analyses were done. Results:Both forms of visualization therapy were more effective than supportive therapy alone in reducing patients’ depression, anxiety and quality of life.Modified VT proved to be significantly more effective in improving patients’ anxiety and quality of life. Conclusion: Visualization is a valuable therapeutic option for reduction of psychological distress and improving quality of life of breast cancer patients.In order to be more effective, the images used need to be modified according to the sociocultural background and individual needs of the patients.

Keywords: breast cancer, visualization therapy, quality of life, anxiety, depression

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Authors: Levent Dumenci, Laura A. Siminoff

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Health literacy has been shown to predict a variety of health outcomes. Reliable identification of persons with limited cancer health literacy (LCHL) has been proved questionable with existing instruments using an arbitrary cut point along a continuum. The CHLT-6, however, uses a latent mixture modeling approach to identify persons with LCHL. The purpose of this study was to estimate two-week and six-month stability of identifying persons with LCHL using the CHLT-6 with a discrete latent variable approach as the underlying measurement structure. Using a test-retest design, the CHLT-6 was administered to cancer patients with two-week (N=98) and six-month (N=51) intervals. The two-week and six-month latent test-retest agreements were 89% and 88%, respectively. The chance-corrected latent agreements estimated from Dumenci’s latent kappa were 0.62 (95% CI: 0.41 – 0.82) and .47 (95% CI: 0.14 – 0.80) for the two-week and six-month intervals, respectively. High levels of latent test-retest agreement between limited and adequate categories of cancer health literacy construct, coupled with moderate to good levels of change-corrected latent agreements indicated that the CHLT-6 classification of limited versus adequate cancer health literacy is relatively stable over time. In conclusion, the measurement structure underlying the instrument allows for estimating classification errors circumventing limitations due to arbitrary approaches adopted by all other instruments. The CHLT-6 can be used to identify persons with LCHL in oncology clinics and intervention studies to accurately estimate treatment effectiveness.

Keywords: limited cancer health literacy, the CHLT-6, discrete latent variable modeling, latent agreement

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Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob

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Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.

Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus

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Authors: Ines Zemni, Maher Slimane, Jamel Ben Hassouna, Khaled Rahal

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Background: Neurofibromatosis type 1 (NF1) is a genetic disease, which is associated with an increased risk of developing different malignancies including breast cancer. The association between NF1 band breast sarcoma is a rare entity. Herein we present a 25-year-old woman with NF1 who had fibrosarcoma of the left breast. Case presentation: The patient has multiple thoraco-abdominal 'café au lait' spots. Clinical examination showed a lump of the left breast measuring 9 cm of diameter, which was noticed for 6 months. There was a left inguinal mass of 6 cm of diameter. The patient underwent first a left lumpectomy. Histopathological exam revealed a high-grade fibrosarcoma of the left breast measuring 7.5 cm. Three months later, the patient underwent a left mastectomy and excision of the inguinal mass, which was a neurofibroma. An adjuvant chemotherapy and radiation therapy were indicated, but not applied because of the timeout. The patient is now alive after a follow up of 6 years, with no loco-regional recurrence or metastasis. Conclusion: The relationship between NF1 and breast cancer need to be more clarified by further studies. Establishing a specific screening program of these patients may help to make an earlier diagnosis of breast cancer.

Keywords: neurofibromatosis, breast, sarcoma, cancer

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Authors: Meral Huri, Sedef Şahin

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Post-traumatic stress disorder (PTSD) is characterized by psychiatric symptoms and triggered by a terrifying experience which may immediately effect cognitive, affective, behavioral and social skills of the individual. One of the most common noncutaneous cancer among men is prostate cancer. The incidence of psychological stress is quite common in men with prostate cancer. The aim of the study was to explore the PTSD frequency among prostate cancer and define the relationship between occupational participation, coping skills and level of perceived social support among patients with prostate cancer. Forty patients diagnosed with prostate cancer were included in the study. After dividing the patients into two groups ( study/ control) according to type of tumor, we recorded their characteristics and evaluations differences. We evaluated the demographic information form, Structured Clinical Interview for DSM-IV (SCID- I)- Clinical Version for PTSD, Multidimensional Scale of Perceived Social Support, Styles of Coping Inventory and Canadian Occupational Performance Measure (COPM) before and after 1 month from surgery. The mean age of the study group (n:18) was 65.85.6 years (range: 61-79 years). The mean age of the control group (n: 22) was a little bit higher than the study group with mean age 71.3±6.9 years (range: 60-85 years). There was no statistically significant difference between the groups for age and the other characteristics. According to the results of the study, statistically significant difference was found between the level of PTSD of study and the control group. 22% of study group showed PTSD while 13% of the control group showed PTSD (r: 0.02, p<0.001). The scores of study group and control group showed statistically significant difference in five sub-categories of Styles of Coping Inventory. Patients with prostate cancer showed decreased scores in optimistic, seeking social supports and self-confident approach, while increased scores in helpless and submissive sub-categories than the control group (p<0.001). The scores of Multidimensional Scale of Perceived Social Supports of study group and control group showed statistically significant difference. The total perceived social supports score of the study group was 71.34 ± 0.75 while it was 75.34 ± 0.64 for the control group. Total and the sub-category scores of study group were statistically significant lower than the control group. According to COPM, mean scores of occupational participation of study group for occupational performance were 4.32±2.24 and 7.01±1.52 for the control group, respectively). Mean Satisfaction scores were 3,22±2.31 and 7.45±1.74 for the study and control group, respectively. The patients with prostate cancer and benign prostate hyperplasia (BPH) did not show any statistically difference in activity performance (r:0.87) while patients with prostate cancer showed statistically lower scores than the patients with BPH in activity satisfaction (r:0.02, p<0.001).Psycho-social occupational therapy interventions might help to decrease the prevalence of PTSD by increasing associated factors such as the social support perception, using coping skills and activity participation of patients with prostate cancer.

Keywords: activity performance, occupational therapy, posttraumatic stress disorder, prostate cancer

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Authors: Amdy Moustapha Drame, Ilya V. Germashev, E. A. Markushevskaya

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Among the main problems of medicine is breast cancer, from which a significant number of women around the world are constantly dying. Therefore, the detection of malignant breast tumors is an urgent task. For many years, various technologies for detecting these tumors have been used, in particular, in thermal imaging in order to determine different levels of breast cancer development. These periodic screening methods are a diagnostic tool for women and may have become an alternative to older methods such as mammography. This article proposes a model for the identification of malignant neoplasms of the mammary glands by the asymmetry of internal and external thermal imaging fields.

Keywords: asymmetry, breast cancer, tumors, deep learning, thermogram, convolutional transformation, classification

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Authors: David Jurado, Carlos Ávila

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Detection of early signs of breast cancer development is crucial to quickly diagnose the disease and to define adequate treatment to increase the survival probability of the patient. Computer Aided Detection systems (CADs), along with modern data techniques such as Machine Learning (ML) and Neural Networks (NN), have shown an overall improvement in digital mammography cancer diagnosis, reducing the false positive and false negative rates becoming important tools for the diagnostic evaluations performed by specialized radiologists. However, ML and NN-based algorithms rely on datasets that might bring issues to the segmentation tasks. In the present work, an automatic segmentation and detection algorithm is described. This algorithm uses image processing techniques along with the Hough transform to automatically identify microcalcifications that are highly correlated with breast cancer development in the early stages. Along with image processing, automatic segmentation of high-contrast objects is done using edge extraction and circle Hough transform. This provides the geometrical features needed for an automatic mask design which extracts statistical features of the regions of interest. The results shown in this study prove the potential of this tool for further diagnostics and classification of mammographic images due to the low sensitivity to noisy images and low contrast mammographies.

Keywords: breast cancer, segmentation, X-ray imaging, hough transform, image analysis

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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Authors: Hossein Rassi, Alaheh Gholami Roud-Majany, Zahra Razavi, Massoud Hoshmand

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Cervical cancer is multi step disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN)and cervical cancer. In other hand, some of hTERT and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of hTERT genotypes and miR-146a genotypes in cervical cancer. Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of hTERT and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, hTERT ( rs 2736098) GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical cancer in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of hTERT rs 2736098 genotypes and miR-146a rs2910164 genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: polymorphism of hTERT gene, miR-146a rs2910164 polymorphism, cervical cancer, virus

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Authors: Dalia Rimawi, Walid Salameh, Amal Al-Omari, Hadeel AbdelKhaleq

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Predication of Survival time of patients with cancer, is a core factor that influences oncologist decisions in different aspects; such as offered treatment plans, patients’ quality of life and medications development. For a long time proportional hazards Cox regression (ph. Cox) was and still the most well-known statistical method to predict survival outcome. But due to the revolution of data sciences; new predication models were employed and proved to be more flexible and provided higher accuracy in that type of studies. Artificial neural network is one of those models that is suitable to handle time to event predication. In this study we aim to compare ph Cox regression with artificial neural network method according to data handling and Accuracy of each model.

Keywords: Cox regression, neural networks, survival, cancer.

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Authors: Ali A. A. Alqarni, Gamal A. Mohamed, Hossam M. Abdallah, Sabrin R. M. Ibrahim

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Phytochemical investigation of the methanolic extract of aerial parts of Tagetes minuta L. (Family: Asteraceae) using different chromatographic techniques led to the isolation of five compounds; ecliptal (1), scopoletin (2), P-hydroxy benzoic acid (3), patuletin (4), and patuletin-7-O-β-D-glucopyranoside (5) (Figure 1). Their structures were established based on physical, chemical, and spectral data [Ultraviolet (UV), Proton ¹H, Carbon thirteen ¹³C, and Heteronuclear Multiple Bond Correlation (HMBC) NMR], as well as Electrospray Ionization Mass Spectroscopy (ESIMS) and comparison with literature data. Their cytotoxic activity was assessed towards human liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and human colon cancer (HCT116) cancer cell lines using sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards HepG2, MCF7, and HCT116 cells with IC₅₀s ranging from 2.74 to 7.01 μM, compared to doxorubicin (IC₅₀ 0.18, 0.60, and 0.20 μM, respectively), whereas compounds 2, 4, and 5 showed moderate cytotoxic potential with IC50s ranging from 11.71 to 35.64 μM. However, 3 was inactive up to a concentration of 100 μM towards the three tested cancer cell lines.

Keywords: Asteraceae, cytotoxicity, metabolites, Tagetes minuta

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Authors: M. Mohammed Raoof, A. Enkhtaivan, H. Aljuaid

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This study follows the design science research methodology to design and implement a smartphone application artifact. The developed artifact was evaluated through three phases. The System Usability Scale (SUS) metric was used for the evaluation. The designed artifact aims to spread awareness about reducing air pollution, decreasing lung cancer development, and checking the air quality status in Southern California Counties. Participants have been drawn for a pilot study to facilitate awareness of air pollution. The study found that smartphone applications have a beneficial effect on the study’s aims.

Keywords: air pollution, design science research, indoor air pollution, lung cancer, outdoor air pollution, smartphone application

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Authors: Rebecca Dunne, Cormac Small, Geraldine O'Boyle, Nazir Ibrahim, Anisha

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Prostate cancer is the most common cancer among men, excluding non-melanoma skin cancers. It is estimated that approximately 12% of men will develop prostate cancer during their lifetime. Patients with intermediate, high risk, and very-high risk prostate cancer often undergo a combination of radiation treatments. These treatments include external beam radiotherapy with a low-dose rate or high-dose rate brachytherapy boost, often with concomitant androgen deprivation therapy. The literature on follow-up of patients that receive brachytherapy is scarce, particularly follow-up of patients that undergo high-dose rate brachytherapy. This retrospective study aims to investigate the biochemical failure and toxicities associated with triple therapy and external beam radiotherapy given in combination with brachytherapy. Reported toxicities and prostate specific antigen (PSA) were retrospectively evaluated in eighty patients that previously underwent external beam radiotherapy with a low-dose rate or high dose-rate brachytherapy boost. The severity of toxicities were correlated with intra-operative dosing during brachytherapy on ultrasound and CT scan. The results of this study will provide further information for clinicians and patients when considering treatment options.

Keywords: toxicities, combination, brachytherapy, intra-operative dosing, biochemical failure

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Authors: Jamboor K. Vishwanatha

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Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.

Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin

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Authors: Hiroko Komatsu, Kaori Yagasaki

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Background: Cancer-related cognitive impairment is a common problem seen in cancer patients undergoing chemotherapy. Physical activity may show beneficial effects on the cognitive function in such patients. Therefore, we have developed a self-directed home yoga program for cancer patients with cognitive symptoms during chemotherapy. This program involves a DVD presenting a combination of yoga courses based on patient preferences to be practiced at home. This study was performed to examine the feasibility of this program. In addition, we also examined changes in cognitive function and quality of life (QOL) in these patients participating in the program. Methods: This prospective feasibility study was conducted in a 500-bed general hospital in Tokyo, Japan. The study population consisted of breast cancer patients undergoing chemotherapy as the initial therapy. This feasibility study used a convenience sample with estimation of recruitment rate in a single facility with the availability of trained nurses and physicians to ensure safe yoga intervention. The aim of the intervention program was to improve cognitive function by means of both physical and mental activation via yoga, consisting of physical practice, breathing exercises, and meditation. Information on the yoga program was provided as a booklet, with an instructor-guided group yoga class during the orientation, and a self-directed home yoga program on DVD with yoga logs. Results: The recruitment rate was 44.7%, and the study population consisted of 18 women with a mean age of 43.9 years. This study showed high rates of retention, adherence, and acceptability of the yoga program. Improvements were only observed in the cognitive aspects of fatigue, and there were serious adverse events during the program. Conclusion: The self-directed home yoga program discussed here was both feasible and safe for breast cancer patients showing cognitive symptoms during chemotherapy. The patients also rated the program as useful, interesting, and satisfactory. Participation in the program was associated with improvements in cognitive fatigue but not cognitive function.

Keywords: yoga, cognition, breast cancer, chemotherapy, quality of life

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Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala

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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.

Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab

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