scholarly journals Serum Cathepsin H as a Potential Prognostic Marker in Patients with Colorectal Cancer

2004 ◽  
Vol 19 (4) ◽  
pp. 289-294 ◽  
Author(s):  
A. Schweiger ◽  
I.J. Christensen ◽  
H.J. Nielsen ◽  
S. Sørensen ◽  
N. Brünner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Marker ◽  
Malignant Disease ◽  
Prognostic Information ◽  
Protein Levels ◽  
Risk Of Death ◽  
Weak Association ◽  
Cathepsin H ◽  
Significant Difference ◽  
Lysosomal Cysteine Protease

Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly increased in patient sera, the median level was 8.4 ng/mL versus 2.1 ng/mL in 90 healthy blood donors (p<0.0001). A weak association of cathepsin H levels was found with patient age (p=0.02) but not with Dukes’ stage, sex, or the level of carcinoembryonic antigen (CEA). In survival analysis a significant difference was found between the group of patients with low cathepsin H (first tertile) who had a poor prognosis and the remaining patients (p=0.03). The risk of patients was further stratified when cathepsin H levels were combined with CEA. Patients with high CEA and low cathepsin H had the highest risk of death with a hazard ratio of 2.72 (95% CI 1.73–4.28), p<.0001. Our results show that the prognostic information of cathepsin H differs from that of the related cathepsins B and L and suggest different roles during the progression of malignant disease.

Survival among colorectal cancer patients with a history of previous cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16146-e16146
Author(s):  
Sandi Pruitt ◽  
David E. Gerber ◽  
Hong Zhu ◽  
Daniel Heitjan ◽  
Bhumika Maddineni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Population Based ◽  
Competing Risk ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

e16146 Background: A growing number of patients with colorectal cancer (CRC) have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. We examined the impact of previous cancer on overall and cancer-specific survival in a population-based cohort of patients diagnosed with incident CRC. Methods: We identified patients aged ≥66 years and diagnosed with CRC between 2005-2015 in linked SEER-Medicare data. For patients with and without previous cancer, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression, separately by CRC stage, while adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident CRC. Results: Of 112,769 CRC patients diagnosed with incident CRC, 15,935 (14.1%) had a previous cancer – most commonly prostate (32.9%) or breast (19.4%) cancer, with many 7505 (47.1%) diagnosed ≤5 years of CRC. For all CRC stages except IV in which there was no significant difference in survival, patients with previous cancer had modestly worse overall survival (hazard ratios from fully adjusted models range from 1.11-1.28 across stages; see Table). This survival disadvantage was driven by deaths due to previous cancer and other causes. Notably, most patients with previous cancer had improved CRC-specific survival. Conclusions: CRC patients who have survived a previous cancer have generally worse overall survival but superior CRC-specific survival. This evidence should be considered concurrently with concerns about trial generalizability, low accrual, and heterogeneity of participants when determining exclusion criteria. [Table: see text]

Colorectal cancer ovarian metastases

2021 ◽  
pp. ijgc-2020-002328
Author(s):  
Lucas W Thornblade ◽  
Ernest Han ◽  
Yuman Fong
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Disease Free Survival ◽  
Ovarian Metastasis ◽  
Term Survival ◽  
Ovarian Metastases ◽  
Risk Of Death ◽  
Significant Difference ◽  
Disease Free

ObjectiveOvarian metastases occur in 3%–5% of patients with colorectal cancer. The role of oophorectomy in that setting continues to be debated. We aimed to assess the survival of women treated with metastasectomy for ovarian metastasis.MethodsRetrospective cohort study of patients in the California Cancer Registry (2000–2012) with stage IV colorectal cancer and ovarian metastases. Pathology other than adenocarcinoma was excluded. Adjusted Cox-proportional hazard analysis was applied to assess the risk of death.ResultsA total of 756 patients with synchronous ovarian metastases and 516 patients with metachronous ovarian metastases form the basis of this analysis. Median follow-up for the synchronous cohort was 21 months (IQR: 8–36). Median overall survival was 23 months (IQR: 10–42). Estimated 5-year survival reached 17% and 10-year survival was 8%. There was a significant difference in unadjusted survival between patients with solitary ovarian metastasis (median overall survival: 51 months) compared with those who had both ovarian and extraovarian metastases (20 months) (log-rank test, P<0.0001). For patients with solitary ovarian metastases, the 5- and 10-year survival was 46% and 31%, respectively. Among patients with synchronous ovarian metastases, longer unadjusted survival was observed after oophorectomy (median overall survival: 24 months) compared with no oophorectomy (18 months, log-rank P=0.01). For patients with metachronous diagnoses of colorectal cancer ovarian metastasis, the median disease-free survival was 19 months. The median survival after resection of metachronous ovarian metastases was 25 months, with the survival directly related to the disease-free interval until metastasis. For patients with resected metachronous ovarian metastases, the 5- and 10-year post-metastasectomy survival was 14% and 5%, respectively.ConclusionsPatients with colorectal cancer ovarian metastasis have favorable long-term survival. Survival rates are higher if the tumor is isolated to the ovary or if metachronous to the primary cancer.

Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

2004 ◽  
Vol 19 (4) ◽  
pp. 289-294 ◽  
Author(s):  
A. Schweiger ◽  
I.J. Christensen ◽  
H.J. Nielsen ◽  
S. Srensen ◽  
N. Brunner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Marker ◽  
Cathepsin H

scholarly journals A Truncated NRIP1 Mutant Amplifies Microsatellite Instability of Colorectal Cancer by Regulating MSH2/MSH6 Expression, and Is a Prognostic Marker of Stage III Tumors

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4449
Author(s):  
Pascale Palassin ◽  
Marion Lapierre ◽  
Samuel Pyrdziak ◽  
Antoine Wagner ◽  
Régine Stehle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Marker ◽  
Dominant Negative ◽  
Interacting Protein ◽  
Chemotherapy Drugs ◽  
Protein Levels ◽  
Msh6 Gene ◽  
Dominant Negative Activity

Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.

scholarly journals Improved Survival After Multidisciplinary Team Decision-Making for Patients with Advanced Gastrointestinal Cancer: A Multicenter, Prospective, Noninterventional, Controlled Study

2021 ◽  
Author(s):  
Qi Zhang ◽  
Ye Zhou ◽  
Lijie Song ◽  
Weijia Fang ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Survival Analysis ◽  
Gastrointestinal Cancer ◽  
Multidisciplinary Team ◽  
Controlled Study ◽  
Term Survival ◽  
Risk Of Death ◽  
Implementation Rate ◽  
Significant Difference

Abstract BackgroundFormal multidisciplinary team (MDT) discussions in clinical practice require time and space with unclear survival benefits for advanced gastrointestinal patients. This study aimed to investigate the long-term survival of patients with advanced gastrointestinal cancer after multidisciplinary team (MDT) decision-making.Materials and MethodsFrom June 2017 to June 2019, continuous MDT discussions on advanced gastrointestinal cancer were conducted in ten medical centers in China. MDT decisions and actual treatment received by patients were prospectively recorded. The primary endpoint was the difference in overall survival (OS) between patients in MDT decision implementation and nonimplementation groups. The secondary endpoints included the implementation rate of MDT decisions and subgroup survival analysis. ResultsA total of 461 MDT decisions of 455 patients were included in this study. The implementation rate of MDT decisions was 85·7%. Sex and previous treatment had an impact on MDT decision-making. The OS was 24·0 months and 17·0 months, respectively, in MDT decision implementation and nonimplementation groups. The implementation of MDT decisions significantly reduced the risk of death in the univariate analysis. The subgroup analysis showed a significant difference in survival analysis of patients with colorectal cancer, but no significant difference was found in patients with gastric cancer. The rate of secondary MDT discussion was very low. ConclusionMDT discussion can prolong the OS of patients with advanced gastrointestinal cancer, especially colorectal cancer. Scheduling of the next MDT discussion in time is necessary when the disease condition changes.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

The JPJDF has Synergistic Effect with Fluoropyrimidine in the Maintenance Therapy for Metastatic Colorectal Cancer

2020 ◽  
Vol 15 (3) ◽  
pp. 257-269
Author(s):  
Xiaoling Fu ◽  
Yanbo Zhang ◽  
Lisheng Chang ◽  
Dengcheng Hui ◽  
Ru Jia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Synergistic Effect ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Advanced Colorectal Cancer ◽  
Treated Group ◽  
Induction Treatment ◽  
Chemotherapeutic Regimen ◽  
Significant Difference

Background: Maintenance chemotherapeutic regimen with low toxicity is needed for metastatic colorectal cancer. A recent patent has been issued on the spleen-strengthening and detoxification prescription (JPJDF), a traditional Chinese herbal medicinal formula with anti-angiogenesis effect. The clinical effect of JPJDF on the maintenance treatment of advanced colorectal cancer has not been evaluated. Objective: This study aims to evaluate the effectiveness and safety of JPJDF in combination with fluoropyrimidine compared to fluoropyrimidine alone as maintenance therapy for metastatic colorectal cancer. Methods: We applied a prospective, randomized, double-blinded, single center clinical study design. A total of 137 patients with advanced colorectal cancer were recruited. Patients received either Fluoropyrimidine (Flu-treated group, n = 68), or Fluoropyrimidine plus JPJDF (Flu-F-treated group, n = 69) as maintenance treatment after 6-cycle of FOLFOX4 or FOLFORI induction treatment. The primary endpoints were Progression-Free Survival (PFS) and Overall Survival (OS). The secondary endpoints were safety, Performance Status (PS) score and other symptoms. Results: The endpoint of disease progression was observed in 91.7% of patients. The PFS was 5.0 months and 3.0 months in the Flu-F-treated and Flu-treated groups, respectively. The OS was 15.0 months and 9.0 months in the Flu-F-treated and Flu-treated groups, respectively. Some common symptoms, such as hypodynamia, anepithymia, dizziness and tinnitus and shortness of breath, were improved in the Flu-F-treated group. There was no significant difference in the common adverse reactions between the two groups. Conclusion: JPJDF and fluoropyrimidine have synergistic effect in the maintenance treatment of mCRC.

Increse of newly - detected in situ cancers in non-palpable breast lesions

2006 ◽  
Vol 53 (1) ◽  
pp. 73-75
Author(s):  
N. Miletic ◽  
D. Stojiljkovic ◽  
M. Inic ◽  
M. Prekajski ◽  
A. Celebic ◽  
...  
Keyword(s):  
Breast Tissue ◽  
Malignant Disease ◽  
Clinical Stage ◽  
Diagnostic Procedures ◽  
Basal Membrane ◽  
Needle Aspiration ◽  
Screening Mammography ◽  
Significant Difference ◽  
Malignant Lesions

Great importance in detecting cancer in the phase of in situ lays in the fact that the epithelial layer is deprived of blood and lymph vessels, so metastases may develop only when basal membrane has been broken. This paper includes 46 operated women in whom it preoperatively had been verified suspect non-palpable lesion. The preoperative diagnostics included use of high- resolution mammography, aimed mammography, palpatory examination, as well as fine-needle aspiration (FNA), biopsy and cytologic analysis of the sample. The methodology of this work implies the use of stereotaxic marking, specimen mammography and ex-tempore pathohistology analysis. Out of 46 investigated patients in clinical stage T0N0M0, in whom there were no signs of malignant disease, and according to suspect lesion of initial screening mammography, malignant lesions of breast tissue were diagnosed in 19 patients (41%) intraoperatively. Three of these lesions (15,8%) were histopathologically verified as in situ. Comparing our results with data of the Institute of oncology and radiology of Serbia hospital registry (IORS) for the year 2001, from 1173 patients registered with malignant lesions, only 16 ones (1,4%) had in situ cancer, operated on the basis of the suspect mammography of clinical stage T0N0M0. Statistically significant difference was found related to the number of detected cancers in this early phase of the breast malignant disease. This limits surgical intervention to tumorectomy, with preservation of the remaining breast tissue, what brings to healing, justifying in that way, screening examinations and routine application of the most contemporary diagnostic procedures.

scholarly journals ORNITHINE DECARBOXYLASE ACTIVITY AS A PROGNOSTIC MARKER FOR COLORECTAL CANCER

2007 ◽  
Vol 53 (1) ◽  
pp. 1-9 ◽  
Author(s):  
YUTAKA HOSHINO ◽  
SHINYA TERASHIMA ◽  
YASUSHI TERANISHI ◽  
MASANORI TERASHIMA ◽  
MICHIHIKO KOGURE ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Marker ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Ornithine Decarboxylase Activity

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

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