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  1. Tseng M, Vellayappan B, Choong R, Appalanaido GK, Soon YY
    Transl Cancer Res, 2020 Jan;9(Suppl 1):S23-S28.
    PMID: 35117945 DOI: 10.21037/tcr.2019.07.23
    Background: To determine if PMRT for elderly patients (>65 years old) with intermediate risk breast cancer (T1-2N1, T3N0) improves outcomes.

    Methods: We performed a systematic review and meta-analysis to compare the effects of PMRT to no PMRT for elderly patients with intermediate-risk breast cancer. We searched PubMed for eligible studies from Jan 2008 to Dec 2018. We assessed the methodological quality of the included studies using the ROBINS-I tool and performed the meta-analysis with random effects model. The primary outcome of interest was overall survival (OS); secondary outcomes were breast cancer specific survival (BCSS), loco-regional (LRR) and distant disease recurrence (DDR).

    Results: We found 2 retrospective cohort studies with 743 patients directly comparing PMRT to no PMRT. Both studies were judged to have serious risk of bias in their methodological quality. The pooled results suggest that PMRT was associated with a 20% relative reduction in the hazard in death, ranging from 41% relative reduction, a substantial negative association to 10% relative increase, a small positive association (HR 0.80, 95% CI: 0.59-1.1, P=0.62, I2=0%). PMRT was also associated with a 17% relative reduction in the hazard for breast cancer related death, ranging from 52% relative reduction, a substantial negative association to 41% relative increase, a substantial positive association (HR 0.83, 95% CI: 0.48-1.41, P=0.48, I2=0%). One study did not observe any significant differences in LRR and DDR between the two groups.

    Conclusions: The survival benefits from PMRT in unselected elderly patients with intermediate risk breast cancer is unclear. Further research to better select elderly patients who may benefit from PMRT is warranted. Patients with a multiple pathological risk factors suggestive of high risk of loco-regional recurrence post-mastectomy should consider PMRT.

  2. Al-Rudayni AHM, Gopinath D, Maharajan MK, Menon RK
    Transl Cancer Res, 2020 Apr;9(4):3126-3134.
    PMID: 35117676 DOI: 10.21037/tcr.2020.02.77
    Oral mucositis (OM) is one of the most prominent side effects of cancer treatment and is believed to have a significant impact on the quality of life (QoL) of the affected patients. However, measurements for the investigation of OM is plagued by heterogeneity in symptoms that varies with the type of cancer or the treatment. We aimed to carry out a qualitative assessment of the current evidence on the impact of OM on QoL in patients undergoing oncologic treatment. A systematic search for studies evaluating the impact of OM on QoL was performed in MEDLINE and Embase databases from inception to December 2018 using the MeSH terms for the keywords "Antineoplastic", "Stomatitis", and "Quality of life". Studies were initially assessed based on the selection criteria and underwent a selection process based on the title and abstract followed by a full text review. Data extraction was performed into a standardized data collection form to collect data pertaining to the author/year, study design, study characteristics, mucositis assessment, QoL assessment and results. A qualitative assessment was performed. A total of 459 articles were selected after removal of duplicates. Following the full text review, only ten articles qualified for the systematic review based on the selection criteria. Several studies have identified a correlation between the severity of mucositis and reduction in QoL. The impact of OM on QoL extend beyond the local oral complications and has been shown to affect the physical, emotional, and psychological functional domains. However, heterogeneity in the study parameters and evaluation (cancer types, treatment regimens, chosen time points (during or after therapy) and the instruments used for QoL measurements) does not permit a robust assessment of the impact of OM on QoL. A standardized approach to the measurement of oral mucositis and evaluation of QoL is required to enhance the utility of QoL data in patients afflicted with oral mucositis following cancer treatment.
  3. Li H, Zhang Y, Teh MS, Limaye S, Cavalcante FP, Shen JB
    Transl Cancer Res, 2023 Sep 30;12(9):2371-2378.
    PMID: 37859736 DOI: 10.21037/tcr-23-1175
    BACKGROUND: Male breast cancer (MBC) is a rare disease and differs from female breast cancer (FBC) in clinicopathological and immune tissue types. Given the limited research on MBC due to its rarity, an understanding of the shared and distinct features of MBC and FBC is vital for formulating efficacious treatment strategies.

    METHODS: Data of patients diagnosed with metastatic breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2012 to 2017 were analysed. Chi-square test was used to compare clinicopathological characteristics between male and female patients. Kaplan-Meier analysis was utilized to compare differences in overall survival (OS).

    RESULTS: A total of 2,858 patients with MBC were studied, 134 of whom had distant metastasis. Compared with 8,698 patients with metastatic FBC, a higher proportion of metastatic MBC patients had tumors located in the center of the breast, received surgical treatment, and had bone + lung metastasis. Survival analysis revealed no difference in OS between metastatic MBC and FBC patients (P=0.27), but there was a significant difference in OS between metastatic and nonmetastatic MBC (P=0.004). Compared with metastatic FBC, MBC patients with bone metastasis alone, lung metastasis alone, liver metastasis alone, and bone + lung metastasis also had worse prognosis (P=0.021, 0.019, 0.024, 0.011, respectively).

    CONCLUSIONS: Metastatic MBC has unique clinicopathological disease features and patterns of metastasis. No significant difference between the survival of metastatic MBC and FBC patients was observed. Distant metastasis was an independent risk factor impacting the prognosis of MBC patients.

  4. Sivakumar S, Gupta AA, Nik Mohd Rosdy NMM, Venkiteswaran A, Raj AT, Awan KH
    Transl Cancer Res, 2020 Apr;9(4):3092-3100.
    PMID: 35117672 DOI: 10.21037/tcr.2020.01.09
    BACKGROUND: This study aims to qualitatively and quantitatively review the association between Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC).

    METHODS: PubMed, Scopus, and Web of Science databases were searched using the keywords "EBV or Epstein Barr virus and Oral cancer or Oral squamous cell carcinoma" for published case-control studies in the English language upto August 2019.

    RESULTS: The search yielded 985 articles out of which 966 articles were excluded by screening their titles and abstracts as they were irrelevant or duplicates. Based on the full-text assessment of the remaining 19 articles, only 7 satisfied the inclusion criteria and were included in the qualitative analysis, out of which only 4 were compatible to be included in the meta-analysis. The diagnostic modalities used included immunohistochemistry, in situ hybridization and polymerase chain reaction. The diagnostic targets included latent membrane protein (LMP)-1, EBV determined nuclear antigen-1, EBV-encoded small non-polyadenylated RNA-2. The meta-analysis showed that there is an association between the EBV and OSCC.

    CONCLUSIONS: Determining the association of EBV with OSCC is highly tedious due to the contrasting data obtained from individuals' studies which in turn is due to the wide variations in the sensitivity and specificity of the diagnostic modalities used and diagnostic targets selected. Although the meta-analysis revealed an association between EBV and OSCC, the number and the quality of the studies included in the meta-analysis are limited, thus the association requires further validation for any conclusive inference.

  5. Luo Y, Chen Y, Ai C, Huang X, Perna F, Kale BJ, et al.
    Transl Cancer Res, 2024 Nov 30;13(11):6273-6281.
    PMID: 39697751 DOI: 10.21037/tcr-24-1543
    BACKGROUND: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM. However, in lenalidomide-resistant MM, it is not yet known whether the abnormally high expression of PARP1 is involved in the occurrence of drug resistance, and whether the inhibition of PARP1 can reverse lenalidomide resistance. The aim of this study was to investigate the mechanism of PARP1 promoting lenalidomide-resistant in MM patients.

    METHODS: Samples of bone marrow from patients with MM who were sensitive or resistant to lenalidomide were collected. The expression levels of PARP1 at the messenger RNA and protein levels were detected through polymerase chain reaction and western blot. MM cell lines were cultivated in vitro, cell lines resistant to lenalidomide were screened out, and the expression levels of PARP1 in the resistant cell lines were detected. The apoptosis level was also detected in the lenalidomide-resistant MM cell lines treated with a PARP1 inhibitor. The proliferation rates of the two groups of cells at different time points were evaluated by mono-methyl terephthalate (MMT) experiments. Finally, the effect of PARP1 on the proliferation of lenalidomide-resistant MM through the microRNA-192-5p-AKT signaling pathway was analyzed.

    RESULTS: In the lenalidomide-resistant cell lines, the expression level of PARP1 was higher, the proliferation more rapid, and the apoptosis rate was lower than lenalidomide-sensitive cell lines. Additionally, the activated AKT pathway was suppressed by downregulating the expression of microRNA-192-5p. MM resistance can be inhibited to some extent by impacting PARP1.

    CONCLUSIONS: PARP1 is involved in the production of lenalidomide resistance in MM, and could serve as a potential target for the treatment of MM in the future.

  6. Ma Y, Noh CIC, Pare R
    Transl Cancer Res, 2025 Feb 28;14(2):1157-1170.
    PMID: 40104731 DOI: 10.21037/tcr-24-1315
    BACKGROUND: The cell death pathway, including apoptosis, autophagy, and necroptosis, plays an essential role in hepatocellular carcinoma (HCC) progression and outcome. However, the integration of the three cell death pathways into a prognostic signature has not yet been reported in HCC. This study aimed to investigate the association among cell death-related genes (CDRGs), prognosis, immune microenvironment, and immune checkpoint.

    METHODS: The RNA expression profiles and corresponding clinical data of HCC were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC). Univariate Cox regression analysis was performed to identify the relevant prognostic genes, and Lasso Cox regression analysis was employed to calculate the risk score. The relationship between the risk score and clinicopathological characteristics, immune cell infiltration, and immune checkpoint expression was analyzed.

    RESULTS: A prognostic risk model for HCC was constructed from the identified CDRGs and patients were subgrouped based on risk score. High-risk patients for HCC exhibited a significantly lower overall survival (OS) rate than the low-risk patients. In addition, the receiver operating characteristic (ROC) curve demonstrated the predictive ability of the risk score. Patients in the high-risk group exhibited lower immune cell infiltration and higher expression levels of immune checkpoint molecules.

    CONCLUSIONS: The cell death-related signature established herein provides a valuable predictive tool for survival and holds promise as a potential therapeutic biomarker for HCC.

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