ORAL CANCER NOVEL TREATMENTS AND APPROACHES

The aggressive tumour known as oral cancer can metastasize, produce a high fatality rate, and infect nearby tissue. Surgery, chemotherapy, and radiation therapy, for example, are common treatment options that, when used in clinical settings, have both minimal drawbacks and major side effects. Currently, oral therapeutic medication delivery using targeted drug administration is proving to be effective. In recent years, an effective alternative therapy known as “nanomedicine,” or using nanoplatforms to deliver drugs for the treatment of cancer, has evolved. Thanks to the use of nanoplatforms, drug delivery to the tumour site can be done precisely and with minimal drug degradation in the body. As a result, the drug's toxicity is diminished, its concentration at the tumour site is elevated, and its distribution to other organs is kept to minimum. We present a contemporary review of the development medication delivery targeted for the treatment of oral cancer in this article different oral delivery systems, including as cyclodextrins, liposomes, hydrogel-based forms, and nanolipids are highlighted and explored. Biomimetic systems, such as therapeutic vitamins, proteins, exosomes, and virus-like particles, with a focus on cancer treatment, are also described. The study concludes with a brief analysis of future applications for nanoplatforms in the treatment of oral cancer

ROLE OF CIRCULATING MIR-21 EXPRESSION PROFILES AND THEIR EMERGENCE AS POTENTIAL BIOMARKERS IN ORAL SQUAMOUS CELL CARCINOMA

Among the widest range of prevalent forms of cancer is oral carcinoma, which can develop anywhere in the mouth or even on the lips. Although there have been many advances in cancer treatment, the expected lifespan for OSCCs have indeed increased marginally. The load of OSCC is anticipated to increase in the near future, yet there is no sign of relief in view. Tumorigenesis is just one of the many physiological processes that can be controlled by microRNAs, a class noncoding endogenous RNAs. Several fibrosis disorders have been linked to miR- 21, and it has been utilised to distinguish oral and tongue cancer from healthy individuals. Studies empirically highlighted the significance of these transcripts as a predictor for prediction and diagnosis in OSCCs. Therefore, the present review summarizes the expression levels of miRNAs in OSCCs and evaluates their functioning in the progression or suppression of cancer. miR-21 can be considered as a prospective candidate for their translational use in OSCCs for early diagnosis prognosis surveillance and tailored treatment which should undergo further validation.

ROLE OF TUMOR MARKERS IN CERVICAL CARCINOGENESIS

Various types of tumor markers are currently being investigated to ascertain their capability in discriminating pre-cancerous lesions of cervix who have tendency for progression. The adequate treatment of such cases will check any chances of occurrence of carcinoma cervix in the population. The micro- RNAs are sensitive tumor markers but their high cost and sophisticated technique make them not feasible to be introduced in any cervical cancer screening program under Indian setup. Other tumor markers like claudins, p16, Ki67 etc are also very expensive. AgNOR pleomorphic counts and micronuclei counts are cheaper, the farmer being more reliable can be introduced in cytological screening program to identify high risk cases and can easily replace costly Human papilloma virus (HPV)- DNA testing.

Comparative Study of Hemoglobin estimation by different methods

Background: Hemoglobin (Hb) estimation is one of the most frequently ordered investigations. Estimation of exact levels is important to stratify the grade of anemia and subsequently direct the necessary treatment. Conventionally, Hb has been estimated using colorimetric method, which is time tested and recommended by the WHO. Now-a-days, the automated method is also becoming a popular method in many hospitals. However, there are not many studies assessing the accuracy of the automated method over the gold standard. Materials and methods: We retrospectively analyzed hemoglobin values in 180 adult patient-samples (18 per batch in 10 batches). Hemolyzed samples were excluded from the study. Blood samples were drawn in vials having K3 EDTA anticoagulants. After a proper mixing, hemoglobin was estimated by automated Sysmex XS-800i. Parallel estimation for Hb content was done manually by spectrophotometer 4010. Results: Patients ranged from ages 20 to 40 years (M:F=102:78). The lowest value recorded by Sysmex XS-800i was 5.8 while the highest value recorded was 18.6 gm%. The mean hemoglobin concentration on Sysmex XS-800i was 12.89. The lowest, highest and mean values recorded by the cyanmethemoglobin method on photometer were 5, 18 and 13.49 gm% respectively. This showed a mean difference of 0.597 and with significant p-value of <0.001. Conclusion: The lowest values of Hb were similar in both the methods but the mean as well as the highest values differed significantly. Our study found an accuracy of 95.57% with the 5 part analyzer when compared to the gold standard colorimetric method.

Intraarticular Involvement By Synovial Sarcoma: First Diagnosed On Synovial Fluid Aspiration

Synovial Sarcoma is a soft tissue neoplasm having incidence 6%- 10%.Malignant cells in synovial fluid aspiration is extremely rare. Only 5%cases have been reported to have joint cavity involvement. We report a case of synovial fluid malignant effusion of knee joint in a 35 year old male who presented with a left popliteal fossa swelling. Synovial fluid aspiration revealed tumor cell clusters with anaplastic morphology .Subsequent biopsy showed spindle cell tumor consistent with synovial sarcoma. This is a rare presentation of synovial sarcoma with the presence of malignant cells in synovial fluid

Dna Topoisomerases: A Review On Their Functionalaspects In Cell Division

DNA is double helical macromolecule which carries all the genetic information and it is usually found enveloped inside a nucleus. The DNA helix relaxes and supercoils itself frequently in order to derive information from the genes during processes like transcription, condensation, replication and recombination, which require mutable or immutable alterations to cause the separation of the two DNA strands. Due to problems caused by the helical structure of DNA, these topoisomerase enzymes perform the required DNA uncoiling. Their role in cell cycle is also significant as their mutation leads to failure of anaphase separation (1, 2). In the present review, the important roles of DNA topoisomerases and their inevitable role in cell growth and cell cycle are discussed viz. how they function in cell proliferation and what are the results when different inhibitors are added to the cells, affecting cell cycle at various checkpoints .

Lung Cancer Stem Cells-An Update

Lung cancer is regarded as one of the most common cancers in the world with a worldwide occurrence of approximately 1.8 million cases and an estimated mortality of 1.6 million in 2012 alone.1 In the United States, there are approximately 2,25,000 new cases of lung cancer with over 1,60,000 deaths annually. Lung cancer is a very serious problem of the Indian subcontinent, especially in the lower socioeconomic subgroups. In India lung carcinoma is the 5th most common tumor and 2nd most common tumor in the males as per the ICMR [Indian Council Of Medical Research] registry of 2002.It accounts for 6.9% of new cancer cases detected each year.3 The importance of study of stem cells and cancer stem cells lays in CSC acting as prognostic and therapeutic markers. It is a known fact that there are innate stem cells present in the lining of the bronchial epithelium, at the carina and alveolar lining which help in regeneration of lungs post injury , however there are present similar cells which post driver mutations are christened CSC and help in cancer survival, growth and chemo resistance. CSC also known as “cancer stem-like cells” (CSLCs), or “tumor-initiating cells” (TICs) are heterogeneous cell population comprising of a small subpopulation of cancer cells with the property of self-renewal and differentiation. CSCs are thought to be responsible for cancer initiation, progression, metastasis, recurrence, and drug resistance.Important CSC under study in lung are, CD 133, ALDH 1, CD 44,ABCG2 etc.

Salivary Egfr As Biomarker For Oral Cancer & Pre-Cancer :A Case Control Study

Oral cancer is one of the leading cause of cancer in India, new diagnostic modalities for early diagnosis and treatment will increase the survival of the patients. The present study was carried out with an aim to evaluate salivary levels of EGFR in oral cancer and pre-cancer as tumor marker. For this purpose an observational case-control study was carried out in which a total of 72 subjects were enrolled.Of these 24 (33.3%) were patients of premalignant oral lesions and 24 (33.3%) were patients of malignant oral lesions& 24 (33.3%) subjects were normal healthy controls. Demographic information and clinical data was obtained, estimation for EGFR was performed in saliva. In premalignant cases, buccal mucosa was the most common site involved (87.50%) whereas in malignant cases tongue was the most common site involved (n=10;41.67%). Mean salivary EGFR levels were higher in malignant cases (0.23±0.17 pg/ml) and low in controls (0.10±0.19 pg/ml). Mean EGFR levels in premalignant cases were 0.12±0.22 pg/ml. statistically, this difference was not significant (p=0.052). Statistically, no significant difference in mean EGFR levels among different TNM stages could be seen (p=0.145). EGFR levels showed a potential to discriminate between malignant and premalignanat cases but this difference was statistical insignificant due to lower sample size.

Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement Detection Using Fluorescene In-Situ Hybridization (FISH) In Lung Cancer Prognostication

Lung cancer is a leading cause of cancer related death worldwide. It is increasing at a very fast rate in both men and women. Some significant mutations occurring at molecular level in lung adenocarcinoma, like ALK, EGFR, KRAS, MET, and, ALK (anaplastic lymphoma kinase) gene mutations for an ALK encoded transmembrane receptor tyrosine kinase domain and subsequently participating in the progression of Non-Small Cell Lung Adenocarcinoma (NSCLC). Some fusion partner genes involved in this process are EML-4, KLC1, KIF5B and TFG. The ALK-EML-4 rearrangement is the second most common oncogenic mutation in the nonsmall cell lung adenocarcinoma. There is 3-7% ALK mutation occurring in early or never-smokers in accompanying NSCLC. The NSCLC with ALK gene mutation generally do not have EGFR or KRAS gene mutation which are also molecular markers, which get mutated in cancer. For the detection of ALK mutation in NSCLC, different types of techniques like Fluorescence in situ Hybridization (FISH), Immunohistochemistry (IHC) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) are being used. On the basis of sensitivity and specificity, FISH is gold standard in detecting the mutation when compared with other methodologies like IHC and RT- PCR. However in the Indian setting, FISH is more expensive and hence not available everywhere. In this review the efficacy of these different techniques in detecting ALK mutation and the detailed interpretation of results obtained with FISH has been discussed. For the treatment of ALK/MET mutated NSCLC patients an orally administered drug, crizotinib drug (tyrosine kinase inhibitor) has been approved by Food and Drug Administration (FDA) of United States. Highly sensitive and specific techniques are used for the detection of ALK gene mutation in NSCLC patients which have to be given for crizotinib treatment.

Chondroid Chordoma of the L5S2 Spinous Process Body: A Rare Case Report

Chordoma are slow growing, locally destructive tumors derived from remnants of notochord. They occur mostly along axial skeleton that is basiocciput and sacrococcygeal area. are biphasic malignant neoplasm possessing elements of both chordoma and cartilaginous tissue, an entity which has better prognosis than classical Chordoma. The tumor is likely to recur and hence diagnostically important for appropriate management. Histopathologically, tumor showed chords or nests of cells with partly vacuolated cytoplasm (physaliferous cells) embedded in a myxoid matrix and extensive cartilage formation with degenerative calcification was seen. Immunohistochemically, tumor was positive for Cytokeratin and EMA and negative for S-100 except for Cartilaginous areas which were S-100 positive. We report a case of Chondroid chordoma in a 50 year male presented with intermittent radiating pain in both leg and backache for 1 year. MRI lumbosacral showing the tumor in posterior elements if L S vertebra. Chondroid chordoma is a distinct entity to be 5 2 discriminated from typical type of Chordoma because of its better prognosis. MRI cannot differentiate between Chondroid chordoma and typical chordoma. Awareness of this rare tumor will avoid misdiagnosis and improve the prognosis. Awide surgical excision coupled with adjuvant radiation is the best treatment in the present case.

Role of human papilloma virus in oral leukoplakia.

BACKGROUND: Controversy surrounds regarding the role of human papillomavirus (HPV) in oral precancerous and cancerous lesions in India where smokeless, tobacco consumption is rampant. AIMS: The present study was carried out with an aim to investigate the presence and type of HPV infection in oropharyngeal leukoplakia and to determine the association of HPV positivity with various patient and lesion characteristics. SETTINGS AND DESIGN: Prospective case series. MATERIALS AND METHODS: A total of fifty confirmed cases of oral leukoplakia (OL), aged 18– 55 years were enrolled in the study. Specimens were obtained from the site of lesion. All the specimens were subjected to histopathological analysis and HPV‑16, 18 detection was done using real‑time polymerase chain reaction technique. RESULTS: Mean age of patients was 34.00 ± 8.85. Majority were males (62%), from middle social class (78%) and were educated up to graduation or above (54%). All the patients had one or more adverse habits (betel, chewing tobacco, smoking and alcohol) with mean duration of disease was 3.53 ± 3.05 years. Five patients (10%) had diabetes. Burning sensation (86%) and trismus (36%) were the reported complaints. Maximum were Stage II (50%), sized 2–4 cm2 (60%), homogenous (70%). Floor of mouth and tongue were most commonly involved sites (50%). Majority had mild dysplasia (58%). Acanthosis (66%), hyperplasia (62%), koliocytosis (40%), and keratosis (98%) were quite common. HPV (16/18) could not be detected in any specimen. CONCLUSIONS: The present study highlighted the fact that association of HPV with oral leukoplakia seems to be overestimated and needs to be reexamined with consensus Human papilloma virus (HPV) primers to detect HPV types with more valid empirical relationships.

Cancer Stem Cells In Breast Cancer: A Review

This paper is written for those women who are affected from breast cancer almost one in eight women in the western world as affected with breast cancer with a total of about one million new cases per year worldwide; of which 35% will die. Breast canricoma is eventually genetically complex entity with approximately 70% of patients with breast cancer has bone metastasis. They are associated with poor prognosis and the available treatment options are very limited. The new perspective of stem cell therapies have shown enhanced promises in the research aspect of the breast carcinoma management and prognosis.

Cancer Cell Viability And Survival In Vitro As Function Of Cell Surface Electric Charge : An Analytical Study

Electrical charge is an indicator of the cellular state of health. In cells, the cell membrane is a leaky dielectric. Capacitors are composed of two conducting sheets separated by a thin layer of insulating material known as a dielectric. Cells contain several forms of biological capacitors, which consist of an insulating material (the membrane) covered on both sides by collection of charged dissolved minerals, which serve the function similar to a conducting metal plate. This means that any condition, illness or change in dietary intake that affects the composition of the cell membranes and their associated minerals can affect and alter cellular capacitance. Healthy cells have a higher whole cell and cytoplasm conductivity and higher membrane capacitance than the malignant cells. The electric charge of cell membranes of mammals is negative at physiological pH. It is well-known that surface of cancer and tumor cells carry negative charge in excess to that of normal cells which is responsible for their increased mobility and invasiveness. The high negative surface charge on malignant cells and trophoblasts may mediate the lack of immune rejection of these cells. Thus, neutralizing or removing the tumor cell negative charge may allow negatively charged lymphocytes to approach and destroy them and thereby, the viability and survival of the cancer cells may be affected at least in vitro. The present study serves to - test this hypothesis on invasive human breast carcinoma cell line MDA-MB-231 (ER ) using specially designed and constructed combination of circuits. Preliminary results showed that out of the 8 designed circuits, sets 1, 2 and 7 were able to produce significant growth inhibition of MDA cells in vitro. The application of electrostatic field through specially designed circuits is unique and has never been reported previously. Our long-term goal is to develop a minimally invasive device that will selectively target and destroy both metastatic and non-metastatic cancer cells in humans. Better understanding of effect of decreasing surface charge density of tumor cells may lead to device effective treatment strategy of human tumors in future.

Clinico-pathological Profile of Bronchogenic Carcinoma Among Females in North India.

Objective. The present study was undertaken to explore the clinico-pathological profile of bronchogenic carcinoma among females. Methods. One hundred and twenty-four female patients with histopathologically proven bronchogenic carcinoma who were hospitalised in the Department of Pulmonary Medicine, King George’s Medical University, Lucknow from July 1985 to February 2007 were retrospectively studied. Results. Their mean age was 61 years; 12.9 % of these were less than 40 years of age. Of these, 79% of female patients of lung cancer were first regarded as pulmonary tuberculosis; 76% belonged to rural area. Use of biomass fuel and kerosene oil exposure was the predominant risk factors evident among the 116 non-smoker women. Adenocarcinoma was observed in 43.5%, followed by squamous cell carcinoma in 33.1% and the remaining 23.4% cases were small cell carcinoma. The majority (77.4%) of non-small cell lung cancer (NSCLC) patients had advanced stage disease (IIIb and IV) and 58 % of small cell lung cancer (SCLC) patients had limited disease and 42 % of SCLC patients had extensive disease at the time of diagnosis. Conclusion. Adenocarcinoma was found to be the most common histopathological type of bronchogenic carcinoma among these females.

Walthard Cell Rest Over Fallopian Tube Mimicking? Brenner Tumor- A Curious & Interesting Case Report

Walthard cell rests are benign cluster of epithelial cells found in connective tissue of fallopian tubes and also seen in the mesovarium, mesosalpinx and ovarian hilus. It was proposed that Walthard cell rests may be a source of Brenner's tumor or primary urothelial cell carcinoma because of similar histogenetic origin of their cells. Here we report a case which not only during gross examination showed peculiar peritubal glistening tiny nodules but also demonstrated attention grabbing clusters of cell on histopathology, mimicking ? A tumor. A diagnosis of Walthard cell rest was made. One should always consider a differential diagnosis as Brenner's tumor (primary) or serosal implant from gynaecological, genitourinary or other tumors before making a confirmatory diagnosis of Walthard cell rest.

Prognostic Impact of CD3 Tumor Infiltrating Lymphocytes in Triple-negative Breast Cancer.

Background: Aim of the present study was to evaluate the prognostic significance of CD3+ tumor infiltrating lymphocyte (TILs) in triple-negative breast cancer (TNBC). Methods: Immunohistochemistry was done with antibodies to CD3 TIL, estrogen receptors (ERs), progesterone receptor (PR) and C-erbB2 in tissue sections of 49 TNBC patients. CD3+ intratumoral and stromal TILs were counted in relation to known clinicopathological factors. Results: Intratumoral CD3+ TILs were significantly associated with stage (p = 0.05) with insignificant association with age, menopausal status, family history, grade and lymph node status. Higher counts of stromal CD3+ TILs were significantly associated with stage (p = 0.05), whereas grade, lymph node status, age, menopausal status and family history were insignificant with CD3+ count. The higher CD3 intratumoral and stromal counts both showed significant association with good prognosis (p 0.05). Conclusion: CD3+ TILs may serve as good prognostic marker in TNBC. The results of present study need further validation on larger sample size.

Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.

BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021). CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

Nuclear factor kappa-B and histopathology of chronic gastritis.

Background: Studies suggest that nuclear factor kappa-B (NFκB) activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. Materials and Methods: This study examines the expression and activity of NFκB in situ in antral biopsies of 42 consecutive patients with immunohistochemical techniques. Results: NFκB was highly expressed in the gastric epithelial cells. The number of cells showing activated NFκB correlated with the activity of gastritis (P < 0.05), a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. There was also a strong inverse association with the presence and grade of atrophy. Conclusion: This correlation is direct evidence of the importance of NFκB dependent signal transduction for neutrophil influx in gastritis. The role of NFκB appears to be only in the initial stages of gastritis, there is no role for the molecule in the development of chronic inflammation or atrophy.

Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance.

Background: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics) stage in Carcinoma Cervix (Ca Cx), and its significance as a prognostic marker, is not clear and needs an in-depth study. Aim: To correlate the blood levels of Lipid Peroxidation (LPO), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Vitamin A and E levels with the clinical stage in Ca Cx. Settings and Design: This is a Prospective Case Control Study. Materials and Methods: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC). Statistical Analysis: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. Results: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. Conclusion: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL).

Risk-factors and strategies for control of carcinoma cervix in India: hospital based cytological screening experience of 35 years.

PURPOSE: Role of risk factors in cervical carcinogenesis and strategies for control of the disease have been assessed from the accumulated cytological data, derived from 35 years of hospital-based screening in Lucknow, North India. MATERIALS AND METHODS: A total of 36,484 women have been cytologically screened during a span of 35 years (April 1971 - June 2005) in the Gynaecology out patient department (OPD) of Queen Mary's Hospital. RESULTS: The frequency of Squamous Intraepithelial Lesion (SIL) and carcinoma was found to be 7.2% and 0.6%, respectively, in the present study. The study revealed high age and parity as a predominant factor in cervical carcinogenesis, while viral sexually transmitted disease (STDs) -human papilloma virus (HPV) and Herpes simplex virus (HSV) were also largely associated with SIL cases. The study emphasized great value of clinically downstaging the cervical cancer by detecting cervical cancer in the early stage. The study also revealed a significant difference in the frequency of SIL in symptomatic and asymptomatic women. CONCLUSION: Based on the analyzed data, it was felt that single lifetime screening, which appears to be the most feasible and affordable mode for control of carcinoma cervix in developing countries like India, should be carried out in all women of high parity irrespective of age (with three or more children) and in older women above the age of 40 years irrespective of parity.