Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer.

Autoantibodies against mitochondrial-derived antigens play a key role in chronic tissue inflammation in autoimmune disorders and cancers. Here, we identify autoreactive nuclear genomic DNA (nDNA)-encoded mitochondrial gene products () recognized by breast cancer (BC) patients' sera as nonself, supporting a direct relationship of mitochondrial autoimmunity to breast carcinogenesis. Autoreactivity of multiple nDNA-encoded mitochondrial gene products was mapped to protein-coding regions, 3' untranslated regions (UTRs), as well as introns.

Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review.

We review here the evidence for participation of mitochondrial autoimmunity in BC inception and progression and propose a new paradigm that may challenge the prevailing thinking in oncogenesis by suggesting that mitochondrial autoimmunity is a major contributor to breast carcinogenesis and probably to the inception and progression of other solid tumors. It has been shown that MNRR1 mediated mitochondrial-nuclear function promotes BC cell growth and migration and the development of metastasis and constitutes a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis. The resemblance of the autoantibody profile in BC detected by IFA with that in the rheumatic autoimmune diseases suggested that studies on the autoantibody response to tumor associated antigens and the characterization of the mtDNA- and nDNA-encoded antigens may provide functional data on breast carcinogenesis.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

Background: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.

Methods: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis.

Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens.

Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB). No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients.

Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis.

Background: The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases.

Methods: We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy.

Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC.

Autoantibodies in breast cancer.

In addition to their historical role, autoantibodies appear promising as biomarkers to facilitate diagnosis, improve patient outcome and decrease mortality in cancer. Autoantibodies may also be useful in the identification of subjects at risk for cancer, that is, those bearing premalignant changes. Numerous studies have demonstrated that cancer serum contains a variety of autoantibodies that react with autologous cellular antigens, that is, tumor-associated antigens.

Serologic laboratory findings in malignancy.

Autoantibodies are extremely promising diagnostic and prognostic biomarkers of cancer, and have the potential to promote early diagnosis and to make a large impact by improving patient outcome and decreasing mortality. Moreover, autoantibodies may be useful reagents in the identification of subjects at risk for cancer, bearing premalignant tissue changes. Great efforts are being made in many laboratories to validate diagnostic panels of autoantibodies with high sensitivity and specificity that could be useful in a clinical setting.

New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

Background: Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects.

Rare cause of thoracic myelopathy: ossified ligamentum flavum.

Myelopathy due to ossification of ligamentum flavum was first described in 1938 by Anzai (J Jpn Orthop Assosc. 1938;13:305-316). This is a rare condition that has been described mostly in the far east, most commonly in Japan (Miyasaka et al, Am J Neuroradiol.

Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis.

A plethora of promising breast cancer-associated autoantigens have been cloned by immunoscreening cDNA expression libraries with breast cancer sera or identified using proteomics, yet no biomarkers, whether individual autoantigens or panels of antigens developed using antibody-based methods have been validated and incorporated to routine oncologic practice for the early diagnosis of breast cancer. Recently, the addition of genomics, proteomics and high throughput technology to traditional immunological techniques has revived the interest in this field, and some of the most promising breast cancer autoantigens are in the process of being validated prospectively in large cohorts of patients with breast cancer. In addition, some of the identified breast cancer-associated autoantigens are recognized by T-cells and may prove to have a role in the treatment of breast cancer in the future.

Improved approach to identify cancer-associated autoantigens.

The failure to identify biomarkers of clinical significance for cancer diagnosis and prognosis generated a great deal of skepticism in regard to the usefulness of autoantibody-based methods. SEREX was a major advancement in immunoscreening that resulted in the identification of a large group of autoantigens recognized by cancer sera. However, few SEREX-defined autoantigens have proven to have definitive diagnostic value in clinical practice.

Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the lung and of the head and neck.

Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share some important risk factors, but differ substantially in terms of prognosis and treatment. A pulmonary nodule developing in patients with surgically cured HNSCC may pose a diagnostic dilemma. Markers able to distinguish these two common malignancies would be of major clinical importance.

Paraneoplastic polyarthritis in an ovarian teratoma.

A 34-year-old woman presented to the rheumatology clinic with severe low back pain and arthralgia; later she developed bilateral knee pain and swelling, with limitation in ambulation and minimal improvement with nonsteroidal antiinflammatory drugs. Two weeks later she developed pain on the volar aspect of the right wrist and on the hypothenar region of the right hand. Examination showed swelling and tenderness of the right hypothenar region, tenderness and decreased flexion and extension of the right wrist, and bilateral knee effusions.

Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer.

We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens.