Plasma Levels of Decorin Increased in Patients during the Progression of Breast Cancer

Decorin (DCN), an extracellular matrix proteoglycan found in tumor surrounding tissues, is a natural inhibitor of tumor cell proliferation and invasion. We conducted a cross-sectional observation study to evaluate the association of the pathological stage with the levels of DCN in plasma or tumor surrounding tissue. Among 118 patients who underwent breast surgery, 35 were designated as carcinoma in situ (Stage 0), 39 were Stage I, and 44 were Stage II or III. The stromal expression of DCN was quantified using a semiquantitative digital image analysis after immunohistochemical staining. The concentration of DCN was evaluated with a specific ELISA. As we have previously shown, stromal DCN expression was attenuated in the patients with Stage I, whereas stromal and plasma DCN was elevated paradoxically in those with Stage II/III. The elevated plasma DCN is an independent predictive factor of Stage II/III by the multivariate logistic regression analysis. The plasma level of DCN was negatively correlated with stromal DCN expression only in patients with advanced disease (Stage II/III). The plasma level of DCN could become a useful biomarker for patients in the advanced stages. Extensive studies and further assessments are warranted for evaluating the prognostic significance and tumor characteristics to understand the clinical significances of stromal and systemic DCN.

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Immunocytochemical markers in stage I lung cancer: relevance to prognosis.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.8.2858 ◽

1997 ◽

Vol 15 (8) ◽

pp. 2858-2865 ◽

Cited By ~ 191

Author(s):

U Pastorino ◽

S Andreola ◽

E Tagliabue ◽

F Pezzella ◽

M Incarbone ◽

...

Keyword(s):

Lung Cancer ◽

Multivariate Analysis ◽

Cox Model ◽

Statistical Significance ◽

Prognostic Significance ◽

Stage I ◽

Laminin Receptor ◽

Independent Predictive Factor ◽

Time To Recurrence ◽

Egfr Expression

PURPOSE This study investigated the frequency of the expression and prognostic significance of a panel of immunocytochemical markers in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 515 cases of pathologic stage I NSCLC were analyzed. The median follow-up time of surviving patients was 102 months. The following immunocytochemical markers were tested: blood group A and precursors of blood antigens; laminin receptor; c-erbB1/epidermal growth factor receptor (EGFR) and c-erbB2/Neu; BCl2; p53; and angiogenesis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biologic markers using the Cox model for multivariate analysis. RESULTS The pathologic tumor extension (pT) represented the most powerful prognostic factor for survival (P = .0008) and time to recurrence (P = .0007). None of the immunocytochemical markers emerged as an independent predictive factor for survival. Bcl2-positive tumors showed a better time to recurrence (P = .03), but the difference lost statistical significance in the multivariate analysis. Of interest, in the group of 137 patients classified as pT1N0, both EGFR expression and nonangiogenic type of vascular pattern were associated with a poorer survival (P = .02). However, data derived from subset analysis must be interpreted cautiously. CONCLUSION Our findings do not support a relevant prognostic role of immunocytochemical markers in NSCLC. The evidence is not sufficient to alter clinical practice or even to restrict clinical trials of adjuvant treatments to predefined biologic subsets of patients.

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Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.160 ◽

2005 ◽

Vol 43 (9) ◽

Cited By ~ 16

Author(s):

Aikaterini Sfiridaki ◽

Spiros Miyakis ◽

George Tsirakis ◽

Athanassios Alegakis ◽

Andreas M. Passam ◽

...

Keyword(s):

Multiple Myeloma ◽

Matrix Metalloproteinase ◽

Bone Turnover ◽

Interleukin 6 ◽

Turnover Rate ◽

Stage I ◽

Stage Ii ◽

Disease Stage ◽

Bone Resorption Marker ◽

Metalloproteinase 9

AbstractMultiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption.Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78±91.27 vs. 59.25±33.09 ng/mL, p<0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p<0.001, p<0.03, p<0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p<0.0001, p<0.01, respectively). MMP-9 levels were lower in patients compared with controls (p<0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p<0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p<0.03, p<0.003, p<0.002, p<0.003 and p<0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation.

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745 PB 079 SINK SIZE IN GAs-TREATED AND POLLINATED RABBITEYE BLUEBERRY FRUITS

HortScience ◽

10.21273/hortsci.29.5.539g ◽

1994 ◽

Vol 29 (5) ◽

pp. 539g-539

Author(s):

Raouel Cano-Medrano ◽

Rebecca L. Darnell

Keyword(s):

Cell Size ◽

Fruit Set ◽

Fruit Size ◽

Cell Number ◽

Cross Sectional Area ◽

Stage I ◽

Stage Ii ◽

Sectional Area ◽

Cross Sectional ◽

Small Fruit

Exogenous applications of GA, have induced pathenocarpic fruit set in blueberry; however, size of GA,-treated fruit is smaller than pollinated fruit. The small fruit size in GA3-treated fruit may be related to either cell number and/or cell size. Thus, these parameters were examined throughout development in pollinated, non-pollinated and GA3-treated fruits. Fruit growth followed a double sigmoid pattern. During Stage I (0-25 DAA), fruit size in GA,-treated, pollinated, and non-pollinated fruits averaged 0.33, 0.39, and 0.16 g, respectively. There was little change in fruit size in Stage II (25-45 DAA). At ripening, fruit size averaged 1.7 g for GA,-treated and 2.6 g for pollinated fruits. Non-pollinated fruit abscised in Stage II. At anthesis, mesocarp cell number averaged 9910 cells per median cross sectional area and remained constant up to ripening. In Stage I, cell size in G A3-treated and pollinated fruits increased 7X and 9X respectively. Cell size in both fruit types increased 1.5X and 2.8X during Stage II and Stage 111, respectively. Fruit cell number was set at anthesis and differences in fruit size were due to differences in cell ellongation in Stage I.

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An inverse stage-shift model to estimate the excess mortality and health economic impact of delayed access to cancer services due to the COVID-19 pandemic

10.1101/2020.05.30.20117630 ◽

2020 ◽

Cited By ~ 2

Author(s):

Koen Degeling ◽

Nancy N. Baxter ◽

Jon Emery ◽

Fanny Franchini ◽

Peter Gibbs ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Time Horizon ◽

Treatment Initiation ◽

Stage I ◽

Stage Ii ◽

Disease Stage ◽

Life Years ◽

Life Years Lost ◽

Excess Deaths

AbstractBackgroundDecreased cancer incidence and reported changes to clinical management indicate that the COVID-19 pandemic will result in diagnostic and treatment delays for cancer patients. We aimed to develop a flexible model to estimate the impact of delayed diagnosis and treatment initiation on survival outcomes and healthcare costs based on a shift in the disease stage at treatment initiation.MethodsThe stage-shift model estimates population-level health economic outcomes by weighting disease stage-specific outcomes by the distribution of stages at treatment initiation, assuming delays lead to stage-progression. It allows for extrapolation of population-level survival data using parametric distributions to calculate the expected survival in life years. The model was demonstrated based on an analysis of the impact of 3 and 6-month delays for stage I breast cancer, colorectal cancer and lung cancer patients, and for T1 melanoma, based on Australian data. In the absence of patient-level data about time to stage progression, two approaches were explored to estimate the proportion of patients that would experience a stage shift following the delay: 1) based on the relation between time to treatment initiation and overall survival (breast, colorectal and lung cancer), and 2) based on the tumour growth rate (melanoma). The model is available on http://stage-shift.personex.nl/.ResultsA shift from stage I to stage II due to a 6-month delay is least likely for colorectal cancer patients, with an estimated proportion of 3% of the stage I patients diagnosed in 2020 progressing to stage II, resulting in 11 excess deaths after 5 years and a total of 96 life years lost over a 10-year time horizon. For breast and lung cancer, progression from stage I to stage II due to a 6-month delay were slightly higher at 5% (breast cancer) and 8% (lung cancer), resulting in 25 and 43 excess deaths after 5 years, and 239 and 373 life years lost over a 10-year time horizon, respectively. For melanoma, with 32% of T1 patients progressing to T2 disease following a 6-month delay, the model estimated 270 excess death after 5 years and 2584 life years lost over a 10-year time horizon.ConclusionsUsing a conservative 3-month delay in diagnosis and treatment initiation due to the COVID-19 pandemic, this study predicts nearly 90 excess deaths and $12 million excess healthcare costs in Australia over 5 years for the in 2020 diagnosed patients for 4 cancers. If the delays increase to 6 months, excess mortality and cost approach nearly 350 deaths and $46 million in Australia. More accurate data on stage of disease during and after the COVID-19 pandemic are critical to obtain more reliable estimates.

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Results of a stage-based protocol for the treatment of retinoblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.5.1532 ◽

1996 ◽

Vol 14 (5) ◽

pp. 1532-1536 ◽

Cited By ~ 91

Author(s):

E Schvartzman ◽

G Chantada ◽

A Fandiño ◽

M T de Dávila ◽

E Raslawski ◽

...

Keyword(s):

Overall Survival ◽

Optic Nerve ◽

Stage Iv ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Disease Stage ◽

Hematogenous Metastasis ◽

Intrathecal Therapy ◽

Orbital Mass

PURPOSE To describe the treatment of retinoblastoma at a single institution using a prospective protocol based on histopathologic staging. PATIENTS AND METHODS We included 116 consecutive patients (101 eligible, 46 bilateral) from August 1987 to December 1993. Treatment was enucleation or conservative therapy for intraocular disease (stage I patients). Stage II patients (orbital or postlaminar invasion) received vincristine, cyclophosphamide, and doxorubicin for 57 weeks. Patients with orbital mass and extension beyond the cut end of the optic nerve also received orbital radiotherapy (45 Gy). The latter received intrathecal therapy. In those with CNS (stage III) or hematogenous metastasis (stage IV), cisplatin and etoposide were added along with cranial (in patients with a CNS mass and prophylactically in stage IV) or craniospinal (in patients with positive CSF) radiotherapy. RESULTS The median follow-up time was 39 months (range, 12 to 84). The overall survival rate was 0.84. Survival rates according to stage were as follows: stage I probability of overall survival [pOS] = 0.97) (alive/total), 59 of 60; stage II (pOS = 0.85) including patients with scattered episcleral cells, three of three; orbital mass, one of one; postlaminar invasion up to and beyond the cut end of optic nerve, 10 of 11 and 11 of 14, respectively; of stage III (pOS = 0), zero of six; and stage IV (pOS = 0.50), three of six. Only those patients with preauricular adenopathy as the only metastatic site survived in the latter group. Acute toxicity was mild. CONCLUSION Chemotherapy is not warranted to prevent systemic metastasis for intraocular disease. Patients with extraocular orbital disease and had a good outcome with this therapy. Patients with metastatic disease fared poorly, except for those with isolated malignant preauricular adenopathy.

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Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.668 ◽

1999 ◽

Vol 17 (2) ◽

pp. 668-668 ◽

Cited By ~ 135

Author(s):

Stephen L. Graziano ◽

Gary P. Gamble ◽

Nancy B. Newman ◽

Lynn Z. Abbott ◽

Michelle Rooney ◽

...

Keyword(s):

Median Survival ◽

Squamous Cell ◽

Early Stage ◽

Prognostic Significance ◽

Stage I ◽

Stage Ii ◽

Small Cell Lung ◽

Ras Mutations ◽

Significant Difference ◽

Resected Stage

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

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Real-world evidence of glycemic control among patients with type 2 diabetes mellitus in India: the TIGHT study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000654 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000654 ◽

Cited By ~ 7

Author(s):

Surendra S Borgharkar ◽

Soma S Das

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Microvascular Complications ◽

Stage I ◽

Stage Ii ◽

Hypoglycemic Agents ◽

Oral Hypoglycemic Agents ◽

Cross Sectional ◽

Antidiabetic Therapy

ObjectiveTo determine glycemic control in adult patients with type 2 diabetes receiving antidiabetic therapy as part of routine healthcare in India.Research design and methodsThis was a retrospective analysis of cross-sectional data of patients with type 2 diabetes receiving oral hypoglycemic agents (OHAs) with or without insulin between 2015 and 2017. We assessed proportion of patients with uncontrolled glycemia and performed logistic regression to evaluate its association with various risk factors and microvascular complications.ResultsA total of 55 639 eligible records were identified; mean age of patients was 54.31 (±11.11) years. One-third of the study population had microvascular complications, predominantly neuropathy. Nearly 76.6% of patients had uncontrolled glycated hemoglobin (HbA1c) ≥7% (53 mmol/mol); 62% of these patients had HbA1c between 7% and 8% (53–64 mmol/mol). Glycemic control from combination of OHAs with or without insulin varied between 14.2% and 24.8%. In multivariate analysis, factors statistically associated with uncontrolled glycemia were obesity (OR: 1.15), hypertension (stage I OR: 1.65 and stage II OR: 2.73) and diabetes duration >5 years (OR: 1.19) (p<0.001). Similarly, the odds of having any microvascular complication increased with duration of diabetes (past 1–2 years, OR: 1.67; 2–5 years, OR: 2.53; >5 years, OR: 4.01; p<0.0001), hypertension (stage I, OR: 1.18 and stage II, OR: 1.34; p<0.05) and uncontrolled HbA1c (OR: 1.28; p<0.0001).ConclusionsIndian population with type 2 diabetes has a high burden (76.6%) of poor glycemic control. This study highlights the need for early implementation of optimum diabetes pharmacotherapy to maintain recommended glycemic control, thereby reducing burden of microvascular complications.

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Plasma L-dopa in the diagnosis of malignant melanoma.

Clinical Chemistry ◽

10.1093/clinchem/32.1.159 ◽

1986 ◽

Vol 32 (1) ◽

pp. 159-161 ◽

Cited By ~ 12

Author(s):

B A Faraj ◽

V M Camp ◽

D R Murray ◽

M Kutner ◽

J Hearn ◽

...

Keyword(s):

Malignant Melanoma ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Disease Stage ◽

Tyrosine Metabolism ◽

The Mean ◽

Mean Concentration ◽

Normal Controls ◽

Active Disease

Abstract We determined the concentration of L-dopa in the plasma of 98 patients with biopsy-proven melanoma, a dermatological neoplasm that is characterized biochemically by abnormal tyrosine metabolism. For 21 patients previously diagnosed as having melanoma but who were clinically free of disease (stage I), the mean concentration of L-dopa in plasma, 1.01 (SD 0.12) micrograms/L, was not significantly different from that of 32 normal controls, 1.23 (SD 0.16) micrograms/L. However, L-dopa was increased significantly (p less than 0.001) in the plasma of all of 65 patients with active disease (stage II), 2.08 (SD 0.46) micrograms/L, and was highest in 12 patients with stage III malignant melanoma, 8.40 (SD 3.50) micrograms/L. The development of metastases in four patients with stage II melanoma was accompanied by an increase in the concentration of plasma L-dopa. These studies suggest that measurement of plasma L-dopa may be useful in the diagnosis of melanoma.

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Ribonucleotide reductase subunit 2 (RRM2) to predict shorter survival in resected stage I-III non-small cell lung cancer (NSCLC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21065 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21065-e21065

Author(s):

Erika Rijavec ◽

Maria Giovanna Dal Bello ◽

Graziana Savarino ◽

Claudio Sini ◽

Giulia Barletta ◽

...

Keyword(s):

Ribonucleotide Reductase ◽

Excision Repair ◽

Early Stage ◽

Univariate Analysis ◽

Prognostic Significance ◽

Stage I ◽

Stage Ii ◽

Class Iii ◽

Qrt Pcr ◽

Resected Stage

e21065 Background: Biomarkers can help in identifying patients (pts) with early-stage NSCLC with high risk of relapse and poor prognosis. The aim of this study was to investigate the relationship between the levels of expression of 7 biomarkers, various clinicopathological characteristics and their prognostic significance. Methods: Tumor tissue from 82 radically resected stage I-III NSCLC pts were consecutively collected to investigate the mRNA expression and protein levels of the following biomarkers using quantitative reverse transcriptase real-time PCR (qRT-PCR) and immunohistochemistry (IHC) with a tissue microarray technique: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit 1 (RRM1), RRM2, p53R2, thymidylate synthase (TS) and class III beta-tubulin (β-Tub-III). Results: On a univariate analysis, p53R2 expression was significantly higher in adenocarcinoma (ADK) compared to squamous cell carcinoma (SSC) samples (p=0.002) and in stage I compared to stage II-III (p≤0.001). ERCC1 expression was significantly higher in females compared to males (p=0.03), and β-Tub-III expression was significantly higher in ADK than in SSC (p=0.03). Pts with lower RRM2 expression survived longer than pts with higher RRM2 expression (p=0.069). The multivariate analysis confirmed RRM2 as an independent prognostic marker of shorter survival (p= 0.031). The comparison between survival curves with qRT-PCR and IHC showed similar results with a trend towards longer survival among ERCC1 negative pts, BRCA1 negative pts, p53R2 positive pts and among pts with low levels of RRM1 and RRM2, although the difference was not statistically significant with both methods. qRT-PCR and IHC have shown that β-Tub-III and TS had no significant impact on survival. Conclusions: This is the first study that identifies RRM2 expression as a negative prognostic factor in resected stage I-III NSCLC. Moreover, we have demonstrated the differential expression of p53R2 and β-Tub-III in ADK compared to SSC and higher expression of p53R2 in pts with stage I compared to stage II-III NSCLC.

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Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

Journal of Oncology ◽

10.1155/2016/2196703 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Ehsan Nazemalhosseini Mojarad ◽

Seyed Mohammad Hossein Kashfi ◽

Hanieh Mirtalebi ◽

Mohammad Yaghoob Taleghani ◽

Pedram Azimzadeh ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Prognostic Significance ◽

Tumor Stage ◽

Cross Sectional Study ◽

Stage Ii ◽

Curative Surgery ◽

Cross Sectional ◽

Clinical Prognosis ◽

Distinct Subgroup

The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p=0.03), associated with poorer differentiation (p=0.003) and TNM stage II/III of tumors (p=0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p=0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p=0.04) or in tumors located in the colon (p=0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.

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