Displaying publications 41 - 60 of 85 in total

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  1. Kong YH, Syed Zanaruddin SN, Lau SH, Ramanathan A, Kallarakkal TG, Vincent-Chong VK, et al.
    PLoS One, 2015;10(7):e0134045.
    PMID: 26214683 DOI: 10.1371/journal.pone.0134045
    Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer's aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder's grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management.
    Matched MeSH terms: Disease-Free Survival
  2. Morad Z, Lim TO
    Transplant Proc, 2000 Nov;32(7):1485-6.
    PMID: 11119799
    Matched MeSH terms: Disease-Free Survival
  3. Nesaretnam K, Selvaduray KR, Abdul Razak G, Veerasenan SD, Gomez PA
    Breast Cancer Res, 2010;12(5):R81.
    PMID: 20929592 DOI: 10.1186/bcr2726
    Basic research has indicated that tocotrienols have potent antiproliferative and proapoptotic effects that would be expected to reduce the effect of breast cancer.

    Study site: Hospital Kuala Lumpur
    Matched MeSH terms: Disease-Free Survival
  4. Chan LL, Abdel-Latif ME, Ariffin WA, Ariffin H, Lin HP
    Br J Haematol, 2004 Sep;126(6):799-805.
    PMID: 15352983
    Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.
    Matched MeSH terms: Disease-Free Survival
  5. Walewski J, Hellmann A, Siritanaratkul N, Ozsan GH, Ozcan M, Chuncharunee S, et al.
    Br J Haematol, 2018 11;183(3):400-410.
    PMID: 30168134 DOI: 10.1111/bjh.15539
    Some patients with relapsed/refractory Hodgkin lymphoma (HL) are not considered suitable for stem cell transplant (SCT) and have a poor prognosis. This phase IV study (NCT01990534) evaluated brentuximab vedotin (1·8 mg/kg intravenously once every 3 weeks) in 60 patients (aged ≥18 years) with CD30-positive relapsed/refractory HL, a history of ≥1 prior systemic chemotherapy regimen, who were considered unsuitable for SCT/multi-agent chemotherapy. Primary endpoint was overall response rate (ORR) per independent review facility (IRF). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) per IRF, overall survival (OS), proportion proceeding to SCT and safety. The ORR was 50%, with 12% CR; 47% proceeded to SCT. Median DOR was 4·6 months and median duration of CR was 6·1 months. After a median follow-up of 6·9 and 16·6 months, median PFS and OS were 4·8 months (95% confidence interval, 3·0-5·3) and not reached, respectively; estimated OS rate was 86% at 12 months. Most common adverse events (≥10%) were peripheral neuropathy (35%), pyrexia (18%), diarrhoea and neutropenia (each 10%). Brentuximab vedotin showed notable activity with a safety profile consistent with known toxicities, and may act as a bridge to SCT, enabling high-risk patients who achieve suboptimal response to frontline/salvage chemotherapy/radiotherapy to receive potentially curative SCT.
    Matched MeSH terms: Disease-Free Survival
  6. Balasundram S, Salekan K, Ahmad Shariffuddin FN, Taib NA, Adnan TH
    Asian Pac J Cancer Prev, 2018 Sep 26;19(9):2409-2415.
    PMID: 30255693
    Objective: To gauge surgical outcome in breast cancer patients with particular reference to overall survival and
    recurrence free survival among breast cancer patients in Hospital Sultanah Nora Ismail Batu Pahat, Johor, Malaysia.
    Methods: Patients undergoing ablative breast cancer surgery were identified and clinical records were assessed.
    Inclusion criteria for enrolment were stage I-IV breast malignancy necessitating resection with or without radiotherapy/
    chemotherapy from 2007 to 2013. All individuals had a pre-operative assessment. The post operative assessment period
    ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves. Results: A total of
    121 patients were included in this study, with an age range of 28-78 years. Some 98% had undergone local excision/
    lumpectomy/ mastectomy with axillary clearance. While 81% of patients underwent chemotherapy, only 69% had
    radiotherapy. Tumours were oestrogen receptor positive in 58% of cases and progesterone receptor positive in 62%.
    Local recurrence was detected in 10%. The mean age at diagnosis was 51.3 + 10.4 years. The overall survival analysis
    was based on 22 deaths among the 121 patients (18.2%). Three-year and five-year survival rates were 87.6% and 78.4%,
    respectively. Analysis of recurrence-free-survival (RFS) was based on 12 events among 121 patients. The Kaplan-Meier
    RFS analysis revealed that in 90% of the patients with recurrence, it occurred within 45 months. The five year RFS
    rate was 84.5%. The median time taken from diagnosis to ablative surgery was 51 days (upper limit of 791 days).
    Only distant metastasis was a significant factor that impacted on both overall survival and recurrence-free survival
    (p<0.001). Conclusion: Overall survival among our breast cancer patients in our facility is comparable to other in
    other tertiary centres in the country. A trend for earlier detection was noted.
    Matched MeSH terms: Disease-Free Survival
  7. Chua HH, Tuan Sharif SE, Wan Ismail WFN, Zawawi MSF, Abdullah S
    Asian Pac J Cancer Prev, 2021 Mar 01;22(3):741-747.
    PMID: 33773537 DOI: 10.31557/APJCP.2021.22.3.741
    BACKGROUND: The receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key regulators of bone remodelling in bone oncology, including osteosarcoma. We assessed RANKL immunohistochemical expression in osteosarcoma, its association, and disease-free survival with the patients' clinicopathological characteristics.

    METHODS:   One hundred osteosarcoma cases from 2003 to 2018 in Hospital Universiti Sains Malaysia were retrieved. The tissue samples were stained for RANKL, and the association with the clinicopathological characteristics was evaluated. Staining was interpreted in a semiquantitative scoring system and classified into negative and positive expressions.  Results: Eighty-two cases had a positive expression of RANKL in which 56 and 26 patients were classified as low expression and high expression, respectively. The positive expression of RANKL did not show a significant association with clinicopathological characteristics. However, Kaplan Meier survival analysis showed a significant improvement in the disease-free survival patients who underwent limb salvage surgery (LSS) than amputated patients (p-value 0.002), whereas poorer survival was observed among conventional osteosarcomas compared to non-conventional osteosarcoma (p-value 0.01).

    CONCLUSION: Limb salvage surgery had proven to improve osteosarcoma patients' survival compared to amputation, which could improve overall quality of life in osteosarcoma patients. However, our data did not show a significant association between positive RANKL immunohistochemistry with any of the clinicopathological characteristics and patients' final survival. Further studies may be acquired to understand the suitability of using RANKL immunohistochemistry as prognostication in the management of osteosarcoma patients.

    Matched MeSH terms: Disease-Free Survival
  8. Bee PC, Gan GG, Tai YT, Haris AR, Chin E, Veera SN
    Singapore Med J, 2012 Jan;53(1):57-61.
    PMID: 22252185
    The introduction of imatinib mesylate in 1998 has changed the management of chronic myeloid leukaemia. It is now the first-line therapy for newly diagnosed chronic myeloid leukaemia patients worldwide. However, its long-term survival benefit still needs to be established in clinical setting among Asian patients.
    Matched MeSH terms: Disease-Free Survival
  9. Khan FA, Shukla AN, Joshi SC
    Singapore Med J, 2008 Oct;49(10):759-64.
    PMID: 18946607
    Anaemia is the most common haematological abnormality in cancer patients, and unfortunately, it is often under-recognised and undertreated. The aetiopathology of anaemia in cancer patients is complex and is usually multifactorial. There is enough evidence suggesting that tumour hypoxia in anaemic patients has a negative impact on the treatment outcomes in cancer patients. The use of recombinant human erythropoietin is becoming a new standard of care in cancer patients. Various well-controlled studies have shown that the use of erythropoietin (EPO) increases the haemoglobin level, thereby decreasing the need for frequent transfusions and improving the tumour responses, cancer-free survival and quality-of-life parameters in cancer patients. However, a few recent clinical trials failed to replicate the survival benefit. Hence, a free unrestricted use of EPO is to be avoided. The past belief that anaemia does not matter in cancer patients is now considered invalid and is being seriously challenged. This article aims to present some recent findings on the impact of anaemia on outcomes, with discussion on the possible causes and effects. The benefits of the use of EPO analogues in cancer-related anaemia are also presented.
    Matched MeSH terms: Disease-Free Survival
  10. Azrif M, Leong YK, Aslan NM, Fong KV, Ismail F
    Asian Pac J Cancer Prev, 2012;13(6):2467-71.
    PMID: 22938405
    INTRODUCTION: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes.

    METHODS AND MATERIALS: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 and D15 and either etoposide 100mg/m2 IV D1- D5 and cisplatin 20mg/m2 IV D1- D5 (5 day BEP regimen) or etoposide 165 mg/m2 D1- D3 and cisplatin 50mg/m2 D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed.

    RESULTS: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites.

    CONCLUSION: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.

    Matched MeSH terms: Disease-Free Survival
  11. Yeoh AE, Ariffin H, Chai EL, Kwok CS, Chan YH, Ponnudurai K, et al.
    J Clin Oncol, 2012 Jul 1;30(19):2384-92.
    PMID: 22614971 DOI: 10.1200/JCO.2011.40.5936
    PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.
    PATIENTS AND METHODS: Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.
    RESULTS: Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).
    CONCLUSION: Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.
    Matched MeSH terms: Disease-Free Survival
  12. Liam CK, Ruthranesan M, Lee CH, Pang YK, Chua KT, Lim BK
    Asia Pac J Clin Oncol, 2012 Sep;8(3):267-74.
    PMID: 22897510 DOI: 10.1111/j.1743-7563.2011.01509.x
    To evaluate the response and progression-free survival (PFS) of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor (EGFR) mutation status treated with gefitinib.
    Matched MeSH terms: Disease-Free Survival
  13. El-Sherbieny E, Rashwan H, Lubis SH, Choi VJ
    Asian Pac J Cancer Prev, 2011;12(7):1739-43.
    PMID: 22126556
    BACKGROUND: Nasopharyngeal carcinoma is the third most common cancer among men in Peninsular Malaysia. However, no information is available about the prognostic factors. The objective of this study was to identify factors with an influence on outcome in patients treated in Hospital Kuala Lumpur.

    METHODS: A total of 159 patients with non-metastatic nasopharyngeal carcinoma treated during 2002-2003 in Hospital Kuala Lumpur were included in this study. All received radiotherapy. Fifty three patients were treated with radiotherapy alone, while 106 patients received combination chemotherapy. Overall survival and local recurrence-free survival were analyzed using the Kaplan-Meier method and univariate analysis was performed using the log-rank test.

    RESULTS: This study found out that 5-year overall survival and 5-year local recurrence-free survival rates were 58.6% and 54.2% respectively. The stage specific 5-year overall survival rates were: Stage I, 100%; Stage II; 93.3%, Stage III, 62.7%; Stage IVA, 42.2%; and Stage IVB, 40.6%. On univariate analysis, gender (p<0.05), T-classification (p<0.001), N-classification (p<0.05), stage (p<0.05) and cranial nerve involvement (p<0.001) were found to be significant prognostic factors for 5-year overall survival, while gender (p<0.05) and N-classification (p<0.05) were significant prognostic factors for 5-year local recurrence-free survival.

    CONCLUSION: The overall survival rate of patients for this study was low. The patient factor that significantly affected 5-year overall survival was gender, while disease factors were stage, T-classification, N-classification and cranial nerve involvement.

    Matched MeSH terms: Disease-Free Survival
  14. Peh SC, Gan GG, Lee LK, Eow GI
    Pathol. Int., 2008 Sep;58(9):572-9.
    PMID: 18801072 DOI: 10.1111/j.1440-1827.2008.02273.x
    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is recognized to constitute a heterogenous group of neoplasms. It can be divided into germinal center B-cell-like (GCB) and non-GCB subgroups. The aim of the present study was to evaluate the utility of immunophenotype subgrouping of DLBCL in a cohort of multi-ethnic Asian patients. A total of 84 reconfirmed de novo DLBCL were immunostained for the expression of CD10, BCL-2, BCL-6 and multiple myeloma-1. Thirty-three (39.3%) had the GCB phenotype, and the remainder (60.7%), the non-GCB phenotype. The results concur with most reports using a similar method of stratification. Forty-five patients had complete demographic and phenotype studies and 42 patients did not have rituximab treatment and had sufficient data for survival rate analysis. Similar to other studies, patients with combined low and low-intermediate International Prognostic Index score had better overall survival (P = 0.006). But patients with GCB phenotype did not have better prognosis, and BCL-2 expression was not associated with better prognosis. The expression of BCL-6 was associated with lower overall survival rate (P = 0.038). No apparent difference in overall and disease-free survival was noted between patients with GCB and non-GCB disease. BCL-6 expression by tumor cells appears to be associated with poorer prognosis.
    Matched MeSH terms: Disease-Free Survival
  15. Velaiutham S, Taib NA, Ng KL, Yoong BK, Yip CH
    Asian Pac J Cancer Prev, 2008 Jul-Sep;9(3):445-8.
    PMID: 18990019
    INTRODUCTION: CA15-3 is a well-known tumour marker for breast cancer. Currently it is not recommended for screening or diagnosis of breast cancer and its main application is in monitoring response to treatment in women with metastatic breast cancer. The aim of this study was to correlate serum CA15-3 at presentation with the stage of disease and overall survival in women with breast cancer in the University Malaya Medical Centre.

    METHODS: This is a retrospective study of 437 women who had CA15-3 levels determined at initial presentation of breast cancer to UMMC between Jan 1999 and Oct 2003.

    RESULTS: Of those patients who were adequately staged, CA15-3 was found to be elevated (defined as >51 U/ml) in 0% of Stage 1, 7.9% of Stage 2, 36.7% of Stage 3 and 68.6% of Stage 4 cases. In a subset of 331 patients with survival data, patients with normal CA15-3 had a 85% five year overall survival rate compared to 38% in their counterparts with elevation of the tumor marker. The level of elevation was also significantly related to survival; patients with values more than 200 U/ml exhibited only a 28% five year survival. The association of elevated CA15-3 at initial presentation with poor outcome was maintained over univariate and multivariate analyses.

    CONCLUSION: Estimation of CA15-3 at presentation of breast cancer is important as it is an independent prognostic indicator and may prompt the physician to investigate for metastases if elevated.
    Matched MeSH terms: Disease-Free Survival
  16. Ahmad R, Vaali-Mohammed MA, Elwatidy M, Al-Obeed O, Al-Khayal K, Eldehna WM, et al.
    Int J Mol Med, 2019 Jul 23.
    PMID: 31364730 DOI: 10.3892/ijmm.2019.4284
    The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl‑2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP‑ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase‑3 and caspase‑7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N‑acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.
    Matched MeSH terms: Disease-Free Survival
  17. Abd Hamid IJ, Slatter MA, McKendrick F, Pearce MS, Gennery AR
    Blood, 2017 04 13;129(15):2198-2201.
    PMID: 28209722 DOI: 10.1182/blood-2016-11-748616
    Hematopoietic stem cell transplantation (HSCT) cures the T-lymphocyte, B-lymphocyte, and natural killer (NK)-cell differentiation defect in interleukin-2 γ-chain receptor (IL2RG)/JAK3 severe combined immunodeficiency (SCID). We evaluated long-term clinical features, longitudinal immunoreconstitution, donor chimerism, and quality of life (QoL) of IL2RG/JAK3 SCID patients >2 years post-HSCT at our center. Clinical data were collated and patients/families answered PedsQL Generic Core Scale v4.0 questionnaires. We performed longitudinal analyses of CD3+, CD4+ naive T-lymphocyte, CD19+, and NK-cell numbers from pretransplant until 15 years posttransplant. Thirty-one of 43 patients (72%) survived. Median age at last follow-up was 10 years (range, 2-25 years). Twenty-one (68%) had persistent medical issues, mainly ongoing immunoglobulin replacement (14; 45%), cutaneous viral warts (7; 24%), short stature (4; 14%), limb lymphoedema (3; 10%), and bronchiectasis (2; 7%). Lung function was available and normal for 6 patients. Longitudinal analysis demonstrated sustained CD3+, CD19+, and NK-cell output 15 years post-HSCT. CD4+ naive lymphocyte numbers were better in conditioned vs unconditioned recipients (P, .06). B-lymphocyte and myeloid chimerism were highly correlated (ρ, 0.98; P < .001). Low-toxicity myeloablative conditioning recipients have better B-lymphocyte/myeloid chimerism and are free from immunoglobulin replacement therapy. IL2RG/JAK3 SCID survivors free from immunoglobulin replacement have normal QoL.
    Matched MeSH terms: Disease-Free Survival
  18. Pare R, Soon PS, Shah A, Lee CS
    PLoS One, 2019;14(4):e0214604.
    PMID: 30998679 DOI: 10.1371/journal.pone.0214604
    Breast cancer is a heterogeneous disease displaying different histopathological characteristics, molecular profiling and clinical behavior. This study describes the expression patterns of senescence markers P53, DEC1 and DCR2 and assesses their significance on patient survival as a single or combined marker with P16 or P14 using breast cancer progression series. One thousand and eighty (1080) patients with primary invasive ductal carcinoma, no special type, were recruited through an 11-year retrospective study period. We constructed tissue microarrays of normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient and performed immunohistochemical staining to study the protein expression. Statistical analysis includes Pearson chi-square, Kaplan-Meier log ran test and Cox proportional hazard regression were undertaken to determine the associations and predict the survival outcomes. P53, DEC1 and DCR2 expression correlated significantly with normal, benign, premalignant and malignant tissues with (p<0.05). The expression profile of these genes increases from normal to benign to premalignant and plateaued from premalignant to malignant phenotype. There is a significant association between P53 protein expression and age, grade, staging, lymphovascular invasion, estrogen receptor, progesterone receptor and HER2 whereas DCR2 protein expression significantly correlated with tumour grade, hormone receptors status and HER2 (p<0.05 respectively). P53 overexpression correlated with increased risk of relapse (p = 0.002) specifically in patients who did not receive hormone therapy (p = 0.005) or chemotherapy (p<0.0001). The combination of P53+/P16+ is significantly correlated with poor overall and disease-free survival, whereas a combination of P53+/P14+ is associated with worse outcome in disease-free survival (p<0.05 respectively). P53 overexpression appears to be a univariate predictor of poor disease-free survival. The expression profiles of DEC1 and DCR2 do not appear to correlate with patient survival outcomes. The combination of P53 with P16, rather P53 expression alone, appears to provide more useful clinical information on patient survival outcomes in breast cancer.
    Matched MeSH terms: Disease-Free Survival
  19. Loo SK, Ch'ng ES, Lawrie CH, Muruzabal MA, Gaafar A, Pomposo MP, et al.
    Pathology, 2017 Dec;49(7):731-739.
    PMID: 29074044 DOI: 10.1016/j.pathol.2017.08.009
    DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.
    Matched MeSH terms: Disease-Free Survival
  20. Chatterjee J, Dai W, Aziz NHA, Teo PY, Wahba J, Phelps DL, et al.
    Clin Cancer Res, 2017 07 01;23(13):3453-3460.
    PMID: 27986748 DOI: 10.1158/1078-0432.CCR-16-2366
    Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer.Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses.Results: Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)-confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1+ expression on lymphocytes was associated with improved survival.Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453-60. ©2016 AACR.
    Matched MeSH terms: Disease-Free Survival
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