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Prescription of cancer treatment Modalities in Developing Countries:Results from a Multi-centre Observational Study

Journal of cancer Therapy 2014年第11期5卷 989-999页

作者： Rolando Camacho Diogo Neves Marion Pineros Eduardo Rosenblatt Robert Burton Yaima Galán Feras Hawari Saadettin Kilickap Cláudia Naylor Florian Nicula Jesus Reno Bhawna Sirohi Tatiana Vidaurre Kazem Zendehdel International Atomic Energy Agency ViennaAustria Monash University MelbourneAustralia Ministry of Health La HabanaCuba King Hussein cancer centre AmmanJordan Hacettepe University Oncology centre AnkaraTurkey National cancer Institute Jose Alencar Gomes da Silva Rio de JaneiroBrazil Institute of Oncology Prof.Dr.Ion Chiricuta Cluj-NapocaRomania National Institute of Oncology and Radiobiology La HabanaCuba Tata Memorial Hospital MumbaiIndia National Institute of Neoplastic Diseases LimaPeru cancer Research Center Cancer Institute of IranTehran University of Medical SciencesTehranIslamic Republic of Iran

Background: treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure, equipment, human and financial resources available. Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings. Methods: The intended cancer spe-cific treatment planned and written in the patients’ medical record (treatment prescription) of untreated adult cancer cases (≥18 years of age), excluding non-melanoma skin cancer, was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment (surgery, medical oncology and radiotherapy). Results: A total of 17,713 medical records were reviewed, of which 7106 (54.2%) met the eligibility criteria. Prescription of main cancer treatment modalities were distributed as follows: 57.6% for chemotherapy (n = 4093), 56.8% for surgery (n = 4038), and 46.8% for radiotherapy (n = 3327). There was a predominance of plans consisting of combined treatment modalities over monotherapy (55.2% versus 44.8%). At the time of diagnosis 54.3% of the cancer cases had disease that had spread beyond the primary site, 41.2% were considered as having local disease and in 4.5% of the cases the information on disease extension was unknown. Conclusions: The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries, particularly in middle income countries.

关键词： cancer treatment Developing Countries Health Services Needs and Demand Resource Allocation Observational Study

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Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National cancer centre Singapore experience

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World Journal of Clinical Oncology 2020年第3期11卷 143-151页

作者： Sylwan Rahardja Ryan Ying Cong Tan Rehena Sultana Fun Loon Leong Elaine Hsuen Lim Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore National cancer centre Singapore Singapore 169610Singapore Duke-NUS Medical School Singapore 169857Singapore

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast *** are currently few reports on the pattern of use and value of Pertuzumab in real world *** study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian *** To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in *** A retrospective study of 304 HER2-positive MBC patients seen at National cancer centre Singapore between 2011-2017 was *** and clinical data were extracted from electronic medical *** characteristics and billing data of patients who received Pertuzumab were compared with those who did *** Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline *** a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)*** median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab *** median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardio

关键词： Pertuzumab Chemotherapy Metastatic breast cancer treatment cost

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Molecular signaling in cancer stem cells of tongue squamous cell carcinoma:Therapeutic implications and challenges

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World Journal of Stem Cells 2023年第5期15卷 438-452页

作者： Priyanka Joshi Sanjeev Waghmare Stem Cell Biology Group Cancer Research InstituteAdvanced Centre for Treatment Research and Education in CancerTata Memorial CentreNavi Mumbai 410210India

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality *** oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity *** the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the *** presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival *** agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient *** signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved *** this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

关键词： Head and neck squamous cell carcinoma cancer stem cells Signaling Tongue squamous cell carcinoma

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An active RUNX1-ID1/ID3 axis governs differentiation and chemoresistance of cancer stem cell population in epithelial ovarian cancer cells

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BIOCELL 2022年第1期46卷 75-86页

作者： AJIT CDHADVE PRITHA RAY Imaging Cell Signaling&Therapeutics Laboratory Advanced Centre for TreatmentResearch and Education in CancerTata Memorial CentreNavi Mumbai410210India Homi Bhabha National Institute Mumbai400094India

Progression,relapse,and therapy resistance are the most challenging features of cancer therapy that have been postulated to be driven by cancer Stem Cell(CSC)*** enigmatic subpopulation of cancer cells has therefore emerged as promising therapeutic *** earlier reported enrichment of CSC-like side population(SP)with increasing resistance towards Cisplatin and Paclitaxel either alone or in combination in epithelial ovarian cancer(EOC)*** SP population is a small proportion of the total population of cancer cells characterised with high expression of drug transporters,a unique feature of stem cells and thereby can be isolated through their efflux properties of DNA binding *** the bulk non-SP(NSP)population of the cancer cells lack overexpression of the drug transporters and thus can be identified as the dye containing *** this study,we show that increased expression of Runt related transcription factor 1(RUNX1)maintains undifferentiated state of CSC-like SP cells through upregulation of inhibitors of DNA binding/differentiation genes(ID1 and ID3)in late cisplatinpaclitaxel resistant *** RUNX1 expression was found to correlate with decreased median overall survival and disease-free survival in The cancer Genome Atlas(TCGA)data set of high grade serous ovarian cancer(HGSOC)*** protein-protein interaction network analysis of 397 upregulated genes in RUNX1-high samples of TCGA data show significant enrichment of pathways known to negatively regulate CSC *** RUNX1 inhibition not only induces CSC differentiation but also downregulates anti-apoptotic protein BCL2 in both SP and NSP cells and potentiates cytotoxic effects of Cisplatin-Paclitaxel in chemoresistant EOC *** of BCL2 through Venetoclax treatment,a small molecule BH3 mimic,sensitized these cells to platinum taxol ***,our data reveal new regulatory roles by RUNX1 to modulate CSC differentiation via ID

关键词： cancer stem cells Differentiation RUNX1 ID1 ID2 BCL2 Chemoresistance Ovarian cancer

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RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF treatment RESPONSE IN CERVICAL cancerS

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Journal of Innovative Optical Health Sciences 2013年第2期6卷 63-70页

作者： S.RUBINA M.S.VIDYASAGAR C.MURALI KRISHNA Chilakapati Laboratory Advanced Centre for TreatmentResearch and Education in CancerTata Memorial Centre Kharghar 410210India Department of Radiotherapy and Oncology Shirdi Sai Baba cancer Hospital Kasturba Medical College Manipal UniversityManipal 576104India

Concurrent chemoradiotherapy(CCRT)is the choice of treatment for locally adv anced cervical cancers;however,tumors exhibit diverse response to *** prediction of tumor response leads to individualizing treatment *** evaluation criteria in solid tumors(RECIST),the current modality of tumor response assessment,is often subject ive and carried out at the first visit after treatment,which is about four ***,there is a need for better predictive tool for *** spectroscopic techniques,sensitive to molecular alteration,are being pursued as potential diagnostic *** pilot study ains to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT,before taking up extensive in vivo *** vivo Raman spectra were acquired from biopsies collected from 11 normal(148 spectra),16 tumor(201 spectra)and 13 complete response(151 CR spectra),one partial response(8 PR spectra)and one nonresponder(8 NR spectra)*** was analyzed using principal component linear discriminant analysis(PC-LDA)followed by leave-one-out cross-validation(LOO-CV).Findings suggest that normal tissues can be efficiently classified from both pre-and post-treated tumor biopsies,while there is an overlap between pre-and post-CCRT tumor *** of CR,PR and NR tissues were subjected to principal component analysis(PCA)and a tendency of classification was observed,corroborating previous ***,this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

关键词： Concurrent chemoradiotherapy tumor response principal component linear discriminant analysis principal component analysis response evaluation criteria in solid tumors

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Gastric peritoneal carcinomatosis-a retrospective review

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World Journal of Gastrointestinal Oncology 2017年第3期9卷 121-128页

作者： Hwee Leong Tan Claramae Shulyn Chia Grace Hwei Ching Tan Su Pin Choo David Wai-Meng Tai Clarinda Wei Ling Chua Matthew Chau Hsien Ng Khee Chee Soo Melissa Ching Ching Teo Division of Surgical Oncology National Cancer Centre Singapore Dvision of Medical Oncology National Cancer Centre Singapore

AIM To characterize patients with gastric peritoneal carcinomatosis(PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of *** We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral *** We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority(n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175(64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive cancer Network Guidelines for Gastric cancer treatment. Thesepatients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114(66.7%), while cessation of chemotherapy occurred in 157(91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not(10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not(8.7 mo vs 14.6 mo, P < 0.001).CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their

关键词： Peritoneal carcinomatosis Gastric cancer

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Hereditary diffuse gastric cancer: What the clinician should know

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World Journal of Gastrointestinal Oncology 2015年第9期7卷 153-160页

作者： Ryan Ying Cong Tan Joanne Ngeow cancer Genetics Service Division of Medical Oncology National Cancer Centre

Hereditary diffuse gastric cancer(HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E-cadherin gene(CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy. As HDGCs have a prolonged indolent phase, this provides a window of opportunity for surveillance and treatment. Recent findings of other gene defects in CTNNA1 and MAP3K6, as well as further characterization of CDH1 mutations and their pathogenicity will change the way HDGC patients are counselled for screening, surveillance and treatment. This review will bring the reader up to date with these changes and discuss future directions for research; namely more accurate risk stratification and surveillance methods to improve clinical care of HDGC patients.

关键词： Hereditary diffuse gastric cancer CDH1 CTNNA1 MAP3

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Management of asymptomatic primary tumours in stage Ⅳ colorectal cancer: Review of outcomes

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 513-523页

作者： Kate Jessica Wilkinson Wei Chua Weng Ng Aflah Roohullah Liverpool cancer Therapy centre Liverpool Hospital

AIM: To compare outcomes for patients presenting withstage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection(PTR) plus palliative chemotherapy vs primary chemotherapy ***: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primarytumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1 b stage and non-use of modern chemotherapy ***: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated.

关键词： Colorectal cancer Resection Primary tumour Asympto

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Characteristics, management, and outcome of squamous carcinoma of the conjunctiva in a single tertiary cancer center in Jordan

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International Journal of Ophthalmology(English edition) 2018年第7期11卷 1132-1138页

作者： Ata Rajeh Fareed Barakat Samer Khurma Khaleel Al Rawashdeh Osama H.Ababneh Ibrahim AlNawaiseh Mustafa Mehyar Ghadeer Abdeen Imad Jaradat Mona Mohammad Yacoub A.Yousef Department of Surgery (Ophthalmology) King Hussein Cancer Centre (KHCC) Department of Pathology King Hussein Cancer Centre (KHCC) Department of Ophthalmology The University of Jordan and Jordan University Hospital Department of Medical Oncology King Hussein Cancer Centre (KHCC) Department of Radiation Oncology King Hussein Cancer Centre (KHCC)

AIM： To evaluate the features and outcome of management of malignant conjunctival squamous tumors in King Hussein cancer Center（a referral tertiary cancer center in the Middle East）. METHODS： Retrospective case series of 31 eyes for 31 patients with conjunctival squamous neoplasia. Main outcome measures included： age, gender, laterality, tumor location, pathological features, tumor stage, treatment modality, and outcome. RESULTS： Twenty（65%） patients were males and median age was 58 y. Twenty-two（71%） eyes had the tumor in the nasal quadrant. Tumor invasion to nearby structures was seen in 19（61%） eyes, including the cornea, fornix, eyelid, and orbit in 17（55%）, 1（3%）, 2（6%）, and 3（10%） eyes, respectively. Eye salvage was achieved by surgical excision with cryotherapy followed by topical chemotherapy in 28（90%） eyes, and orbital exenteration was necessary in 3（10%） eyes due to orbital tumor invasion. Tumor recurrence was seen in 7（23%） eyes, and the significant predictive factors for recurrence were tumor extension onto the nearby structures（P=0.04）, tumor invasiveness（P=0.038）, and tumor TNM stage（P=0.031）. No significant change in visual acuity was seen, and disease related mortality was 6%（2 patients, both had orbital invasion by invasive squamous carcinoma）. CONCLUSION： Conjunctival squamous carcinoma is more common in males. Advanced American Joint Committee on cancer（AJCC） T-stage, tumor local invasion, more pathologically aggressive tumors, and surgical treatment alone（without adjuvant therapy） are associated with higher risk for recurrence, and orbital invasion is the most important poor prognostic factor for metastasis and death. treatment strategies should be affected by tumor characteristics at presentation.

关键词： conjunctiva squamous cell carcinoma metastasis

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