Serum Raman spectroscopy: Prognostic applications in oral cancers.

Background: Loco-regional recurrences attributable to field cancerization and minimal residual cancer, remain prime causes of mortality in oral cancer (OC) subjects. The current study evaluates potential of serum Raman spectroscopy (SRS) to identify recurrence-prone OC subjects.

Methods: Raman spectra of serum from eight healthy subjects (H) and 57 OC subjects (with-recurrence [R], without-recurrence [NR], and with suspicious-lesions [S]), before (BS) and after (AS) surgical excision of tumor were recorded.

Diagnostic and prognostic role of protein and ultrastructural alterations at cell-extracellular matrix junctions in neoplastic progression of human oral malignancy.

Despite advancements in technology and increase in favorable outcomes associated with oral cancer, early detection remains the most significant factor in limiting mortality. The current study aimed to develop early diagnostic and prognostic markers for oral tumorigenesis. Protein and ultrastructural alterations at cell-extracellular matrix (ECM) adhesion junctions were examined concurrently using immunohistochemistry (IHC) and transmission electron microscopy (TEM) on progressive grade of oral carcinomas (n = 285).

Chemokine SDF1 Mediated Bone Regeneration Using Biodegradable Poly(D,L-lactide--glycolide) 3D Scaffolds and Bone Marrow-Derived Mesenchymal Stem Cells: Implication for the Development of an "Off-the-Shelf" Pharmacologically Active Construct.

There is an increasing need for bone substitutes for reconstructive orthopedic surgery following removal of bone tumors. Despite the advances in bone regeneration, the use of autologous mesenchymal stem cells (MSC) presents a significant challenge, particularly for the treatment of large bone defects in cancer patients. This study aims at developing new chemokine-based technology to generate biodegradable scaffolds that bind pharmacologically active proteins for regeneration/repair of target injured tissues in patients.

Multifaceted role of keratins in epithelial cell differentiation and transformation.

Keratins, the epithelial-predominant members of the intermediate filament superfamily, are expressed in a pairwise, tissuespecific and differentiation-dependent manner. There are 28 type I and 26 type II keratins, which share a common structure comprising a central coiled coil α-helical rod domain flanked by two nonhelical head and tail domains. These domains harbor sites for major posttranslational modifications like phosphorylation and glycosylation, which govern keratin function and dynamics.

Role of Electron Microscopy in Early Detection of Altered Epithelium During Experimental Oral Carcinogenesis.

Early detection of altered epithelium can help in controlling the further progression by timely intervention. Alterations in cellular adhesion are one of the hallmarks of cancer progression, which can be detected at the intracellular level using high-resolution electron microscopy. This study aimed to evaluate the role of electron microscopy in the establishment of ultrastructural markers for early detection of altered epithelium using tissues from 4-Nitroquinoline-1-Oxide (4NQO) induced rat tongue carcinogenesis.

Alterations in desmosomal adhesion at protein and ultrastructure levels during the sequential progressive grades of human oral tumorigenesis.

With the aim of developing early diagnostic/prognostic markers for oral cancer, desmosomal adhesion in sequentially progressive grades of tissues from oral normal/disorders (normal, hyperplastic, dysplastic, non-metastatic/metastatic tumours, and metastatic nodes) was investigated at protein and ultrastructural levels using immunohistochemistry and transmission electron microscopy, respectively. The expression of desmosomal proteins was higher in hyperplastic tissues than in normal tissues but was significantly decreased in subsequent progressive stages of the disease. Altered expression of desmosomal proteins was significantly correlated with local recurrence and disease-free survival.

Prognostic significance of elevated serum CD44 levels in patients with oral squamous cell carcinoma.

Background: Availability of reliable methods distinguishing high-risk recurrent tumours from regressive tumours prior to surgery could help in better management of the disease. This study was aimed to estimate pre-surgical serum CD44 concentration and assess the possibility of using it as a non-invasive prognostic tool in oral cancer.

Methods: ELISA was performed on pre-surgical serum samples from 64 primary oral cancer patients and 16 healthy individuals to estimate soluble CD44 levels.

Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients.

Purpose: Pro-inflammatory cytokines such as Interleukin-17A (IL17A) and Interleukin-32 (IL32), known to enhance natural killer and T cell responses, are also elevated in human malignancies and linked to poor clinical outcomes. To address this paradox, we evaluated relation between IL17A and IL32 expression and other inflammation- and T cell response-associated genes in breast tumors.

Methods: TaqMan-based gene expression analysis was carried out in seventy-eight breast tumors.

Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients.

Vimentin is an intermediate filament protein, predominantly expressed in cells of mesenchymal origin, although its aberrant expression is seen in many carcinomas during epithelial mesenchymal transition. In cancer, vimentin expression is associated with the transition from a more differentiated epithelial phenotype to a dedifferentiated state. In view of the perceived role of keratins (Ks) as regulators of differentiation in epithelia, it was important to understand whether vimentin modulates differentiation through the reprogramming of keratins, in transformed cells.

Establishment of 3D Co-Culture Models from Different Stages of Human Tongue Tumorigenesis: Utility in Understanding Neoplastic Progression.

To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium.

Vimentin-mediated regulation of cell motility through modulation of beta4 integrin protein levels in oral tumor derived cells.

Vimentin expression correlates well with migratory and invasive potential of the carcinoma cells. The molecular mechanism by which vimentin regulates cell motility is not yet clear. Here, we addressed this issue by depleting vimentin in oral squamous cell carcinoma derived cell line.

Oral cancer screening: serum Raman spectroscopic approach.

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe.

Prognostic role of Oct4, CD44 and c-Myc in radio-chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice.

Objective: In the present study, we have investigated the prognostic value of known stem cell-associated molecules such as Oct4, CD44 and c-Myc in patients with oral SCC who had received post-surgery radio- and/or chemotherapy.

Materials And Methods: Immunohistochemistry was performed to analyse the expression of Oct4, CD44 and c-Myc in 87 tumour tissues, and the expression profile obtained was correlated with clinicopathological parameters of the patients with oral cancer. Tumourigenic potential of these molecules was also evaluated by in vivo studies.

Recurrence prediction in oral cancers: a serum Raman spectroscopy study.

High mortality rates associated with oral cancers can be primarily attributed to the failure of current histological procedures in predicting recurrence. Identifying recurrence related factors can lead to improved prognosis, optimized treatment and enhanced overall outcomes. Serum Raman spectroscopy has previously shown potential in the diagnosis of cancers, such as head and neck, cervix, breast, oral cancers, and also in predicting treatment response.

Association of differential β-catenin expression with Oct-4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis.

Background: The re-expression of pluripotent markers (Oct-4 and Nanog) and the reactivation of stem cell-related pathways in oral carcinoma have been well researched. However, the relationship between the stem cell signaling molecule β-catenin and pluripotent markers Oct-4 and Nanog in oral cancer is yet to be studied in detail. Therefore, we have investigated the correlation among Oct-4, Nanog, and β-catenin in oral squamous cell carcinoma, which, in turn, could provide valuable insight into its prognostic significance.

Raman spectroscopy of serum: an exploratory study for detection of oral cancers.

Early diagnosis of oral cancers, one of the major cancers, is of utmost importance as 5-year disease-free survival rates are some of the lowest, despite advances in treatment and surgical modalities. In vivo Raman spectroscopy has shown efficacy in the detection of normal, premalignant and malignant lesions and even of early changes such as cancer-field-effects/malignancy-associated-changes. However, the need for a dedicated instrument and stringent laboratory conditions, at all diagnostic centers, limits wide screening applications of this method.

Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.

Background: Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast.

Alterations in keratins and associated proteins during 4- Nitroquinoline-1-oxide induced rat oral carcinogenesis.

Background: Oral squamous cell carcinoma (OSCC) is the sixth largest group of malignancies globally and the single largest group of malignancies in the Indian subcontinent. Despite the advances in treatment and therapeutic modalities the five year survival rate of OSCC has not changed in the last few decades, and remains less than 40%. Several studies have focused on defining molecular markers that can either detect cancer at an early stage or can predict patient's outcome.

Loss of keratin 8 phosphorylation leads to increased tumor progression and correlates with clinico-pathological parameters of OSCC patients.

Background: Keratins are cytoplasmic intermediate filament proteins expressed in tissue specific and differentiation dependent manner. Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression, invasion and poor prognosis in human oral squamous cell carcinomas (OSCCs).

Prognostic value of tissue polypeptide antigen in oral squamous cell carcinoma.

Human oral cancer has a high risk of locoregional relapse which is difficult to diagnose early due to lack of prognostic markers. We and others have shown aberrant expression of cytokeratin (CK) 8 and 18 in human oral cancer. Aberrant supra-basal expression of CK19 has been shown earlier.

Cytokeratin fragments in the serum: their utility for the management of oral cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Oral cancer is the most predominant malignancy in the Indian subcontinent due to the widespread habits of chewing tobacco and related products. Patients with oral tumours have a high risk of early locoregional relapse.

Implications of cytokeratin 8/18 filament formation in stratified epithelial cells: induction of transformed phenotype.

The cytokeratin (CK) pair 8 and 18 is normally expressed in all simple epithelia. This pair is not normally seen in stratified epithelial cells. Squamous cell carcinomas derived from stratified epithelia show anomalous expression of this CK pair.