22 The potential of serum autoantibodies against type III collagen in cancer

BackgroundAutoantibodies are classically associated with autoimmune diseases but have recently emerged as attractive cancer biomarkers as they can be easily assessed in serum. Certain autoantibodies have been shown to promote cancer while others contribute to the body’s defense against it. Cancer progression is associated with excessive remodeling of the extracellular matrix (ECM) and collagen, but little is known about the role of autoantibodies against collagen in cancer. To investigate autoreactivity against collagen in cancer, we developed a novel biomarker assay to quantify autoantibodies against type III collagen products in serum from patients with various solid tumor types and compared levels with those find in healthy controls.MethodsThe presence and levels of autoantibodies against denatured type III collagen were measured in pretreatment serum from 223 patients with bladder cancer (n=20), breast cancer (n=20), colorectal cancer (n=20), head and neck cancer (n=20), kidney cancer (n=20), liver cancer (n=3), lung cancer (n=20), melanoma (n=20), ovarian cancer (n=20), pancreatic cancer (n=20), prostate cancer (n=20), and stomach cancer (n=20), and compared to age-matched healthy controls (n=33). Statistical differences were analyzed using the Kruskal-Wallis test adjusted for Dunn’s multiple comparisons test.ResultsSerum levels of autoantibodies against type III collagen were significantly lower in patients with bladder cancer (p=0.0007), breast cancer (p=0.0002), colorectal cancer (p<0.0001), head and neck cancer (p=0.0005), kidney cancer (p=0.005), liver cancer (p=0.030), lung cancer (p=0.0004), melanoma (p<0.0001), ovarian cancer (p<0.0001), pancreatic cancer (p<0.0001), prostate cancer (p<0.0001), and stomach cancer (p<0.0001) compared to healthy controls. This autoimmunity biomarker could discriminate between cancer and healthy controls with an AUROC value of 0.88 (p<0.0001).ConclusionsIn this study, we observed that cancer patients with different solid tumor types have downregulated levels of circulating autoantibodies directed against type III collagen compared to healthy controls suggesting that autoantibodies against type III collagen and tumor fibrosis may be important for tumor control and eradication. This autoimmunity biomarker may have the potential for studying and monitoring the close relationship between autoimmunity and cancer such as the risk of developing cancer on rheumatoid arthritis immunosuppressant or the risk of developing immune-related adverse events on cancer immunotherapy.Ethics ApprovalThe serum samples in this study were obtained from the commercial vendor Proteogenex and BioIVT, and according to the vendors, sample collection was approved by an Institutional Review Board or Independent Ethical Committee and patients gave their informed consent (Protocol numbers PG-ONC 2003/1 and WIRB® Protocol #20161665). All investigations were carried out according to the Helsinki Declaration.

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Clinical management of cancer: flowcharts

10.1093/med/9780199235636.003.0021 ◽

2011 ◽

Author(s):

Thankamma Ajithkumar ◽

Ann Barrett ◽

Helen Hatcher ◽

Natalie Cook

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Lung Cancer ◽

Ovarian Cancer ◽

Pancreatic Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Hepatocellular Cancer ◽

Small Cell ◽

Small Cell Lung

Bladder cancer 670Breast cancer 671Cervical cancer 672Colon cancer 673Endometrial cancer 674Epithelial ovarian cancer 675Hepatocellular cancer 676Small-cell lung cancer 677Non-small cell lung cancer 678Oesophageal cancer 679Pancreatic cancer 680Prostate cancer 681Rectal cancer 682Stomach cancer ...

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Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives

Frontiers in Pharmacology ◽

10.3389/fphar.2021.772418 ◽

2022 ◽

Vol 12 ◽

Author(s):

Sicon Mitra ◽

Uttpal Anand ◽

Niraj Kumar Jha ◽

Mahipal S. Shekhawat ◽

Suchismita Chatterjee Saha ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Lung Cancer ◽

Ovarian Cancer ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Black Pepper ◽

Piper Nigrum ◽

Molecular Formula ◽

Cycle Arrest

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.

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The Contributions of Improved Therapy and Earlier Detection to Cancer Survival Gains, 1988-2000

Forum for Health Economics & Policy ◽

10.2202/1558-9544.1195 ◽

2010 ◽

Vol 13 (2) ◽

Cited By ~ 8

Author(s):

Eric Sun ◽

Anupam B Jena ◽

Darius Lakdawalla ◽

Carolina Reyes ◽

Tomas J Philipson ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Pancreatic Cancer ◽

Early Detection ◽

Cancer Survival ◽

Policy Implications ◽

Sensitivity Analyses ◽

Lower Percentage ◽

Conditional Survival

Prior literature has documented improvements in cancer survival over time. However, ambiguity remains over the relative contributions of improved treatment and earlier detection to survival gains. Using registry data, we developed a novel framework to estimate the relative contributions of advances in treatment and detection. Our approach compares changes in the probability of early detection, which we interpret as the effects of advances in detection, to improvements in stage-conditional survival, which we interpret as the effects of treatment. We applied this methodology using SEER data to estimate probabilities of early detection and stage-conditional survival curves for several cancers, by race, between 1988 and 2000. Survival increased for all of the cancers we examined, with blacks experiencing larger survival gains than whites for all cancers combined. Our baseline analysis found that treatment advances account for the vast majority of survival gains for all the cancers examined: breast cancer (83%), lung cancer (85%), colorectal cancer (76%), pancreatic cancer (100%), and non-Hodgkins lymphoma (96%). Compared to whites, treatments appear to explain a lower percentage of survival gains for blacks for all cancers combined; breast cancer, NHL, and pancreatic cancer show a higher percentage of survival gains than lung cancer; and roughly the same percentage for the colorectal cancer. These results are robust to sensitivity analyses examining potential length and lead time bias. Overall, our results suggest that while improved treatment and early detection both contributed to the recent gains in survival, the majority of gains from 1988 to 2000 appear to have been driven by better treatment, manifested by improved stage-conditional survival. These results have important policy implications regarding investment in research and development and the evaluation of efforts to improve cancer screening.

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Changes in stage at diagnosis of screenable cancers after the Affordable Care Act.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.6521 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 6521-6521 ◽

Cited By ~ 3

Author(s):

Xuesong Han ◽

Chun Chieh Lin ◽

Ahmedin Jemal

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Cervical Cancer ◽

Cancer Patients ◽

Female Breast Cancer ◽

Stage I ◽

Stage At Diagnosis ◽

Female Breast

6521 Background: Extensive evidence links inadequate insurance with later stage at cancer diagnosis, particularly for cancers that can be detected by screening. The Affordable Care Act (ACA) implemented in 2014 has substantially increased insurance coverage for Americans 18-64 years old. This study aims to examine any changes in stage at diagnosis after the ACA for the following cancers for which screening is recommended for individuals at risk: female breast cancer, colorectal cancer, cervical cancer, prostate cancer, and lung cancer. Methods: We used National Cancer Data Base, a nationally hospital-based cancer registry capturing 70% new cancer cases in the US each year, to identify nonelderly cancer patients with screening-appropriate age who were diagnosed during 2013-2014. The percentage of stage I disease was calculated for each cancer type before (2013 Q1-Q3) and after (2014 Q2-Q4) the ACA. 2013 Q4-2014 Q1 was excluded as a washout/phase-in period. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated using log-binomial models controlling for age, race/ethnicity and sex if applicable. Results: 121,855 female breast cancer patients aged 40-64 years, 39,568 colorectal cancer patients aged 50-64 years, 11,265 cervical cancer patients aged 21-64 years, 59,626 prostate cancer patients aged 50-64 years, and 41,504 lung cancer patients aged 55-64 years were identified. After the implementation of the ACA, the percentage of stage I disease increased statistically significantly for female breast cancer (47.8% vs. 48.9%; PR = 1.02 [95%CI 1.01-1.03]), colorectal cancer (22.8% vs. 23.7%; PR = 1.04 [95%CI 1-1.08]), and lung cancer (16.6% vs. 17.7%; PR = 1.06 [95% CI 1.02-1.11]). A shift to stage I disease was also observed for cervical cancer (47.2% vs. 48.7%; PR = 1.02 [95% CI 0.98-1.06]) although not statistically significant. In contrast, the percentage of stage I decreased for prostate cancer (18.5% vs. 17.2%; PR = 0.93 [95%CI 0.9-0.96]) in 2014. Conclusions: The implementation of the ACA is associated with a shift to early stage at diagnosis for all screenable cancers except prostate cancer, which may reflect the recent US Preventive Services Task Force recommendations against routine prostate cancer screening.

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Distribution of BRCA1/2 germline and somatic alterations across cancer type.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10590 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10590-10590

Author(s):

Jingde Chen ◽

Ming Quan ◽

Zhengqing Yan ◽

Shiqing Chen ◽

Mei Huang ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Ovarian Cancer ◽

Endometrial Cancer ◽

Genomic Dna ◽

Pancreas Cancer ◽

Clinical Laboratory ◽

White Blood Cells ◽

Cancer Type ◽

Tumor Types

10590 Background: PARP inhibitors (e.g. Olaparib or niraparib) have been approved by FDA as a targeted therapy for many tumors harboring germline or somatic BRCA1/2 (g or sBRCA1/2), including ovarian cancer, prostate cancer, breast cancer and pancreases cancer. It is imperative to study the distribution of BRCA1/2 across cancer type. In this study, we aim to assess the landscape of BRCA1/2 alterations in solid tumors and evaluate the feasibility of circulating tumor DNA (ctDNA) tested by next-generation sequence (NGS) as a tool to detect BRCA1/2 alterations. Methods: For tissue specimen, genomic DNA from formalin fixed paraffin-embedded (FFPE) tumor specimens or fresh tumor tissues was used for sequence analysis. Genomic DNA (gDNA) from white blood cells was extracted using the QIAamp DNA Mini Kit (Qiagen). For ctDNA, cell-free DNA libraries were prepared using the KAPA Hyper Prep Kit following the manufacturer’s protocol. The captured libraries were loaded onto a NovaSeq 6000 platform (Illumina) for 100bp paired-end sequencing. The testing was performed in the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) -certified 3D Medicines Library. Results: A total of 27, 835 patients were tested using tumor tissue during Jan. 1th 2017 to June 1th 2020, including 43% (N = 12089) of non-small cell lung cancer, 19% (N = 5357) of colorectal cancer, 8% (N = 2181) of liver cancer, 6% (N = 1621) of gastric cancer, 5% (N = 1479) of biliary tract cancer, 4% (N = 1084) of kidney cancer, 4% (N = 1045) of pancreas cancer, 3% (N = 689) of breast cancer and 2% (N = 599) of ovarian cancer. Across all tumor types, the known or likely deleterious BRCA1/2 alterations were identified in 2147 (7.7%) patients. Ovarian cancer had the highest frequency of BRCA1/2 alteration (23.4%), followed by endometrial cancer (12.7%) and breast cancer (10.6%). BRCA1/2 alteration was found in 8.8% prostate cancer and 4.2% pancreas cancer respectively. Across all tumor types, the known or likely deleterious gBRCA1/2 alterations were identified in 369 (1.3%) patients. Notably, ovarian cancer had the highest frequency of gBRCA1/2 alteration (13.9%), followed by breast cancer (7%), prostate cancer (4.4%) and endometrial cancer (4.1%). No clear hotspot mutations and mutated codons were spread throughout g or sBRCA1/2 mutations. Additionally, among 15699 patients who suffered ctDNA sequencing, any known or likely deleterious sBRCA1/2 alterations were identified in 358 (2%) patients. Similar to the results of tissue sequencing, ovarian cancer had the highest frequency of sBRCA1/2 alteration (16.67%), followed by endometrial cancer (9.68%), prostate cancer (7.18%) and breast cancer (5.58%) in the blood cohort. Conclusions: BRCA1/2 alterations existed across tumor types and the landscape of g or sBRCA1/2 alterations varied according to cancer type. Furthermore, ctDNA can be used as a potential tool to detect BRCA1/2 alterations.

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Oncology Questions and Answers

Mayo Clinic Internal Medicine Board Review Questions and Answers ◽

10.1093/med/9780199985876.003.0008 ◽

2013 ◽

pp. 79-82

Author(s):

Robert D. Ficalora

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Lung Cancer ◽

Ovarian Cancer ◽

Colon Cancer ◽

Multiple Choice ◽

Cancer Breast ◽

Questions And Answers ◽

Board Review ◽

Cancer Côlon

Chapter 8 presents multiple-choice, board review questions on oncology including lung cancer, colon cancer, ovarian cancer, breast cancer, and prostate cancer. Full explanations are provided with the correct answers.

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Comparison of tumor mutational burden across eight types of human cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15170 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15170-e15170

Author(s):

Peng Chen ◽

Cuicui Zhang ◽

Zhaoting Meng ◽

Xing Zhang ◽

Minhui Ge ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Lung Cancer ◽

Pancreatic Cancer ◽

Bile Duct ◽

Liver Cancer ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Duct Cancer ◽

Tumor Types

e15170 Background: Tumor mutational burden (TMB) is an impressive predictive biomarker for immune checkpoint inhibitors therapy, and immunotherapy is one of the most promising methods for cancer treatment. However, the profile of TMB in various types of cancers was still poorly understood. Methods: In this study, genomic profiling of DNA was performed using next generation sequencing from a 539 genes panel in tumor tissues. The TMB was defined as the numbers of SNVs including synonymous and nonsynonymous mutations, and InDels per megabase in coding regions of sequenced genome. TMB-H was defined as highest mutation load quintile (top 20%) in each cancer type. The values of TMB of 874 patients were compared among eight main tumor types including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases by multiple independent samples nonparametric Kruskal-Wallis H test via SPSS v22.0. Results: The median values of TMB in liver cancer, bile duct cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, glioma and lung cancer were 10.29, 8.09, 11.03, 10.29, 5.88, 7.35, 5.88 and 7.35 Muts/Mb, respectively. The cut-off values of TMB-H in corresponding eight solid tumors were 16.18, 19.12, 19.85, 16.18, 10.29, 13.24, 10.29 and 18.38 Muts/Mb, respectively. Based on nonparametric Kruskal-Wallis H test, there were significant differences of median TMB values across eight independent tumor types (χ2 = 26.752, p = 3.693×10−4). Significant differences between patients with colorectal cancer and pancreatic cancer ( p = 0.005) or lung cancer ( p = 0.011) were observed via pairwise comparisons. Conclusions: Our study proved the presence of significant differences across eight cancer types, deepened the knowledge of the cancer-specific of TMB, provided useful information in immunology therapy for East Asian patients with solid tumors. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.

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BIOBOARD

Asia-Pacific Biotech News ◽

10.1142/s0219030311000334 ◽

2011 ◽

Vol 15 (06) ◽

pp. 3-11

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Lung Cancer ◽

Ovarian Cancer ◽

Cancer Treatment ◽

Brain Disorder ◽

Lung Cancer Treatment

AUSTRALIA – Asian Mushrooms Could Help Fight Prostate Cancer AUSTRALIA – New Lung Cancer Treatment Discovered AUSTRALIA – Gene Behind Rare Brain Disorder Identified CHINA – China Bans Controversial Drug for Kids Below 12 INDIA – Ovarian Cancer Treated with Immunotherapy INDIA – Gene Card Tells What Drugs to Avoid INDIA – IISc, Deakin Join Hands to Fight Cancer with Nanotechnology INDIA – Indian Govt to Introduce First Five-in-One Vaccine SINGAPORE – New Test for Pain Tolerence SINGAPORE – NUS Best University for Medicine in Asia OTHER REGIONS — Implant Breakthrough Helps Paraplegic Man Stand Unaided OTHER REGIONS — Scientists Discover Protein that can Halt Spread of Breast Cancer

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Isolation of Circulating Tumor Cells from Multiple Epithelial Cancers with ApoStream® for Detecting (or Monitoring) the Expression of Folate Receptor Alpha

Biomarker Insights ◽

10.4137/bmi.s35075 ◽

2016 ◽

Vol 11 ◽

pp. BMI.S35075 ◽

Cited By ~ 11

Author(s):

Daniel J. O'Shannessy ◽

Darren W. Davis ◽

Kenna Anderes ◽

Elizabeth B. Somers

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Folate Receptor ◽

Healthy Controls ◽

Blood Samples ◽

Folate Receptor Alpha ◽

Lung Cancer Patients ◽

Receptor Alpha

This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream® technology to identify folate receptor alpha (FRα)–positive cells. We demonstrate that FRα+ CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα+ CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRα-expressing cancers. Folate receptor alpha (FRα) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRα expression. The presence of FRα+ CTCs enriched using ApoStream® and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma ( n = 14), breast cancer ( n = 20), ovarian cancer ( n = 6), and squamous lung cancer patients ( n = 6)] and healthy subjects ( n = 20). The data demonstrated that FRα+ CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRα+ CTCs as previously known. We demonstrate that CTCs captured using ApoStream® can be used to detect FRα+ CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRα levels in cancer patients.

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