scholarly journals Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Min-Gu Kang ◽  
Eun-Jeong Won ◽  
Hyun-Woo Choi ◽  
Hye-Ran Kim ◽  
Hyun-Jung Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Clinical Outcome ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Serum Pth ◽  
The Relationship ◽  
Pth Level

We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P=0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.

scholarly journals Prognostic significance of advanced lung cancer inflammation index (ALI) in multiple myeloma patients – a retrospective study

2021 ◽  
Author(s):  
Junxia Huang ◽  
Juanjuan Hu ◽  
Yan Gao ◽  
Fanjun Meng ◽  
Tianlan Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Free Survival ◽  
Factors Influencing ◽  
Independent Risk Factors ◽  
Cancer Inflammation

Abstract Background: Advanced lung cancer inflammation index (ALI) is known to predict the overall survival of patients having some solid tumors or B-cell lymphoma. The study investigates the predictive value of ALI in multiple myeloma (MM) patients and the correlation between ALI and prognosis.Methods: A database of 269 MM consecutive patients who underwent chemotherapy between December 2011 and June 2019 in the Affiliated Hospital of Qingdao University was reviewed. ALI cut-off value calculated before the initial chemotherapy and post 4 courses treatment were identified according to the receiver operating characteristic (ROC) curve, and its association with clinical characteristics, treatment response, overall survival (OS), and progression-free survival (PFS) were assessed.Results: Patients in the low ALI group (n=147) had higher risk of β2 microglobulin elevation, more advanced ISS (International Classification System stage), and TP53 gene mutation, with significantly lower median overall survival (OS; 36.29 vs. 57.92 months, P = 0.010) and progression-free survival (PFS; 30.94 vs. 35.67 months, P = 0.013). Independent risk factors influencing the OS of MM patients were ALI (P = 0.007), extramedullary infiltration (P = 0.001), TP53 (P = 0.020), Plt (P = 0.005), and bone destruction (P = 0.024). ALI (P = 0.005), extramedullary infiltration (P = 0.004), TP53 (P = <0.001), Plt (P = 0.017), and complex chromosome karyotype (P = 0.010) were independent risk factors influencing the PFS of MM patients.Conclusions: ALI is a potential independent risk factor predicting the prognosis of newly diagnosed MM patients.

Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma

2020 ◽  
pp. jclinpath-2020-206868
Author(s):  
Wei Sang ◽  
Jing Xue ◽  
Li-Ping Su ◽  
Abulajiang Gulinar ◽  
Qian Wang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Clinicopathological Parameters ◽  
Low Grade ◽  
Ki 67 ◽  
Free Survival ◽  
Tumour Location ◽  
Spearman Correlation Test ◽  
The Relationship

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.MethodsExpression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.ResultsHigh expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.ConclusionOur research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.

scholarly journals Multiple Myeloma Patients with Lenalidomide-Associated Skin Rash Have a Favorable Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4532-4532 ◽  
Author(s):  
Ayumi Kojima ◽  
Yuka Tanaka ◽  
Yuta Kimura ◽  
Daisuke Tsuchimoto ◽  
Rina Etani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
The Relationship

Abstract Background: Lenalidomide, one of the immunomodulatory drugs, is an important component of treatment for multiple myeloma. Lenalidomide inhibits the proliferation of tumor cells via antiangiogenesis, induces apoptosis and acts directly on the immune system and tumor microenvironment. Immunomodulatory effects of lenalidomide notably stimulate the production of cytokines and activation of T-cells and natural killer cells. Skin rash is a frequent adverse event of lenalidomide. Some studies have shown a correlation between the efficacy of anti-cancer agents such as tyrosine kinase inhibitors and the development of skin rash. However, the relationship between the development of lenalidomide-associated skin rash and its efficacy is unclear. We conducted a retrospective survey to clarify whether development of skin rash correlates with the efficacy of lenalidomide. Materials and Methods: All patients with multiple myeloma who received lenalidomide at 9 hospitals in Japan from July 2009 to December 2015 were serially registered. The chart review was performed for all identified patients to obtain the following information; age, sex, performance status at the initiation of lenalidomide, International Staging System (ISS) classification, prior chemotherapy regimen, tumor response, development of skin rash and clinical outcomes. A log-rank test was used to assess the relationship between the presence of skin rash and survival. A two-sided p < 0.05 was considered statistically significant. This study received approval from the appropriate ethics committees. Results: We identified 215 patients (92 women and 123 men), with a median age was 69 years (range, 39-86 years). Types of myeloma were as follows: 139 patients of IgG, 43 of IgA, and 29 of Bence-Jones protein. ISS was available for 204 patients, and of these, 63, 73, and 68 patients were classified as ISS stage I, II, and III, respectively. The median number of prior therapies was 2 (range, 0-6); 161 (74.9%) and 46 patients (21.4%) had previously received bortezomib and thalidomide, respectively. Fifty patients (23.3%) had undergone previous autologous stem cell transplantation. Sixty-five patients (30.2%) developed a skin rash after lenalidomide initiation, and the median time to onset of skin rash was 12 days. The patients with and without skin rash were similar with respect to age, type of myeloma, and ISS. The median follow-up of survivors was 28.9 months (range, 1.7-80.3 months). The progression-free survival and overall survival were better in patients who had skin rash than in those who did not (p = 0.009 and p = 0.033, respectively) (Figures A and B). Conclusions: In this study, the progression-free survival and overall survival among patients with skin rash during lenalidomide therapy was significantly superior to the patients without skin rash. Lenalidomide-associeated skin rash in patients with multiple myeloma may be a predictive factor of their clinical outcome. Figure Figure. Disclosures Nagai: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Mundipharma KK: Research Funding.

Serum Level Of Parathyroid Hormone Is Associated With Risk Factors and Clinical Outcomes In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5365-5365 ◽  
Author(s):  
Min-Gu Kang ◽  
Min-Joong Jang ◽  
O-jin Lee ◽  
Min-Seok Heo ◽  
Hyun-Woo Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Chromosome Abnormality ◽  
Bone Lesion ◽  
M Protein ◽  
Cell Percentage ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Serum Pth ◽  
Pth Level

Abstract Background Parathyroid hormone (PTH) is synthesized and secreted by the chief cells of the parathyroid gland. PTH has a positive impact on hematopoietic stem cells by indirectly decreasing hematopoietic cell apoptosis, and is currently being investigated as a potential therapeutic to stimulate hematopoiesis and enhance bone marrow engraftment. According to previous study, it was hypothesized that elevated PTH may mediate the induction of multiple myeloma (MM) through the biologic effects of IL-6. However, there was no comprehensive study regarding clinicopathological implications of PTH in MM. This study investigated the pathological and clinical implications of serum PTH in MM patients and relationship with other risk factors of MM. Patients and Methods A total of 115 patients who were newly diagnosed with MM were enrolled between 2006 and 2012. Serum PTH level was measured by automated 2-site chemiluminescent sandwich assay (Abbott Diagnostics). The medical parameters were reviewed for age, sex, PTH, plasma cell percentage in bone marrow, serum M protein, immunoglobulin level, free light chain (FLC) - kappa and lambda, FLC ratio, calcium, creatinine, hemoglobin, albumin, beta-2 microglobulin, lactate dehydrogenase (LDH), international staging system (ISS) stage, international myeloma working group (IMWG) response, chromosome abnormality, bone lesion, treatment outcome, and so on. The collected data was analyzed by PASW 18.0. We performed Spearman’s correlation analysis, Mann Whitney U-test, Kruskall Wallis test, time dependent Cox regression analysis, survival analysis by Kaplan-Meier method, etc. Results Serum PTH level of 115 myeloma patients was 24.7±34.9 (ranged 0.0-284.1) pg/mL. Serum level of IgG, IgM, FLC-lambda, albumin, and LDH was in positive correlation with serum PTH. Age, plasma cell percentage, M protein, IgA, FLC-kappa, FLC ratio, calcium, creatinine, hemoglobin, and beta-2 microglobulin showed negative correlation with PTH. Among those above, IgM (rho=0.190, p=0.045) and calcium (rho=-0.220, p=0.043) revealed statistically significant correlation with serum PTH. Serum PTH level in MM patients was not significantly different according to the group of IMWG response (p=0.450) and ISS stage (p=0.414). Meanwhile, there was no significant difference of PTH according to chromosomal abnormality (p=0.353), bone lesion (p=0.207), and disease progression (p=0.322). Besides, only calcium level was meaningfully different (p=0.016) by the comparison of clinical parameters between MM patient’s group with high PTH level and non-high PTH group (cut-off PTH level=68.3 pg/mL, Mann Whitney U-test). Relative to non-high PTH (<68.3 pg/mL) group, the hazard ratio was higher for group with high PTH level (≥68.3 pg/ml) ([HR] 3.037; p=0.524; 95% CI, 0.100∼92.586; Table 1). With regard to the prognostic implication of serum PTH value, the patient group with above 68.3 pg/mL showed moderate, inferior progression free survival (PFS) than non-high PTH group (median, 5 months vs. 13 months, p=0.056, Fig.1B). However, no overall survival (OS) differences were found between high PTH group and non-high PTH group (Fig. 1A). Interestingly, subgroup analysis showed that patients with high PTH level significantly had an inferior PFS than those with non-high PTH level. In detail, the subgroup were as follows; patients who reached the complete remission (CR) state (N=25) defined by IMWG response criteria at the end of follow up period (median, 3 months vs. 41 months, p=0.001, Fig.1C), patients (N=41) who belonged to ISS stage II (median, 1 months vs. 15 months, p=0.006, Fig.1D), patients (N=97) with no chromosome abnormality (median, 4 months vs. 15 months, p=0.034, Fig.1E), patients (N=28) who have undergone transplantation (median, 3 months vs. 18 months, p=0.009, Fig.1F). Conclusion This study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 169 ◽  
Author(s):  
Cigdem Usul Afsar ◽  
Mehmet Karabulut ◽  
Senem Karabulut ◽  
Safiye Tokgoz Ozal ◽  
Murat Cikot ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Samples ◽  
Baseline Serum ◽  
Free Survival ◽  
The Relationship

Introduction: Pancreatic cancer (PC) is a lethal malignancy. Various diagnostic, predictive, and prognostic biomarkers have been evaluated. This study was conducted to investigate the serum levels of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) in patients with PC and the relationship between tumor progression and known prognostic parameters. Materials and Methods: Serum samples were obtained on first admission before any treatment. Serum NEDD9 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched healthy controls were included in the analysis. Results: In a three year period, 32 patients with a pathologically-confirmed diagnosis of PC were enrolled in this study. The median age at diagnosis was 61 years, range 38 to 84 years; the majority of the patients in the group were men (n = 20, 62.5%). The tumor was located in the head of pancreas in 21 (65.6%) patients. Forty-one percent of 17 metastatic patients who received palliative CTx (chemotherapy) were CTx-responsive. The baseline serum NEDD9 levels were significantly higher in patients with PA than in the control group (p = 0.03). Median OS of the whole group were 27 ± 7.3 weeks. Alcohol intake, performance status, and LDH levels were found to be significant prognostic factors (p = 0.006, p < 0.001, and p < 0.001, respectively). However, serum NEDD9 levels had no significantly effect on progression free survival (PFS) and overall survival (OS) (p = 0.71 and p = 0.58, respectively). Conclusions: NEDD9 is identified as a secretory biomarker for PC but it has no prognostic role.

scholarly journals Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2787-2793 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
C Anasetti ◽  
R Clift ◽  
R Storb ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Treatment Regimens ◽  
Allogeneic Marrow Transplantation ◽  
Total Body ◽  
Beta 2 Microglobulin

Between September 1987 and December 1994, 80 patients with multiple myeloma (MM) received high-dose busulfan and cyclophosphamide without (n = 57) or with modified total body irradiation (n = 23) followed by marrow from allogeneic donors. At transplant, 71% of the patients had disease that was refractory to chemotherapy. Thirty-five patients died of transplant-related causes within 100 days and 11 deaths occurred later. The actuarial probabilities of survival and progression-free survival were .24 +/- 0.17 and .20 +/- 0.10 at 4.5 years. Complete remissions were obtained in 36% of patients who had actuarial probabilities of survival and event-free survival of .50 +/- 0.21 and .43 +/- 0.17 at 4.5 years. In a multivariate analysis, adverse risk factors for outcome endpoints included: transplantation greater than 1 year from diagnosis; beta-2 microglobulin &gt; 2.5 at transplant; female patients transplanted from male donors; patients who had received greater than eight cycles of chemotherapy before transplant and Durie stage 3 disease at the time of transplant. These results indicate that allografting for patients with MM can result in long-term disease-free survival for a minority of patients. Efforts to reduce transplant-related mortality should focus on earlier transplantation, less toxic treatment regimens, better supportive care, and improved prevention and treatment of graft-versus-host disease (GVHD).

scholarly journals Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaoning Gan ◽  
Xiaomiao Lin ◽  
Rongquan He ◽  
Xinggu Lin ◽  
Hanlin Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Subgroup Analysis ◽  
Early Stage ◽  
Progression Free Survival ◽  
Clinical Staging ◽  
Clinicopathological Parameters ◽  
Warning Sign ◽  
Free Survival ◽  
The Relationship ◽  
P16 Expression

p16, encoded by theCDKN2Agene, is a tumor suppressor that has been widely studied in cancer research. However, the relationship of p16 with prognostic and clinicopathological parameters in patients with bladder cancer remains unclear. Data inclusion criteria were articles reporting on the relationship between p16 expression and the prognosis or clinicopathology in patients with bladder cancer. Meta-analyses were performed with Stata software. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the relative risks. The source of heterogeneity was analyzed by subgroup analysis. A total of 37 studies with 2246 cases were included and analyzed. The results identified an important link between downregulated p16 expression and poor prognosis in patients with bladder cancer in terms of recurrence-free survival (RFS), overall survival (OS), progression-free survival (PFS), and some clinicopathological parameters including clinical staging, pathological degree, and lymph node metastasis. Subgroup analysis also showed that low p16 expression could function as a warning sign for RFS and PFS in patients with early-stage (Ta–T1) bladder cancer. In conclusion, p16 might play an essential role in the deterioration of bladder cancer and could serve as a biomarker for the prediction for patients’ progression and prognosis.

scholarly journals Genetic program activity delineates risk, relapse, and therapy responsiveness in multiple myeloma

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Matthew A. Wall ◽  
Serdar Turkarslan ◽  
Wei-Ju Wu ◽  
Samuel A. Danziger ◽  
David J. Reiss ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chromosomal Abnormalities ◽  
Transcriptional Regulatory Network ◽  
Progression Free Survival ◽  
Cross Sectional ◽  
Free Survival ◽  
Extreme Risk ◽  
Transcriptional Regulatory ◽  
Transcription Regulators ◽  
Immunosuppressive Microenvironment

AbstractDespite recent advancements in the treatment of multiple myeloma (MM), nearly all patients ultimately relapse and many become refractory to multiple lines of therapies. Therefore, we not only need the ability to predict which patients are at high risk for disease progression but also a means to understand the mechanisms underlying their risk. Here, we report a transcriptional regulatory network (TRN) for MM inferred from cross-sectional multi-omics data from 881 patients that predicts how 124 chromosomal abnormalities and somatic mutations causally perturb 392 transcription regulators of 8549 genes to manifest in distinct clinical phenotypes and outcomes. We identified 141 genetic programs whose activity profiles stratify patients into 25 distinct transcriptional states and proved to be more predictive of outcomes than did mutations. The coherence of these programs and accuracy of our network-based risk prediction was validated in two independent datasets. We observed subtype-specific vulnerabilities to interventions with existing drugs and revealed plausible mechanisms for relapse, including the establishment of an immunosuppressive microenvironment. Investigation of the t(4;14) clinical subtype using the TRN revealed that 16% of these patients exhibit an extreme-risk combination of genetic programs (median progression-free survival of 5 months) that create a distinct phenotype with targetable genes and pathways.

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