Role Portrayed by Serum NGAL and Vitamin D in Patients with Bone Tumors.

BACKGROUND: Bone tumors are responsible for considerable morbidity and mortality at an early age. Malignant bone tumors are quite aggressive in nature. Thus, an accurate and timely diagnosis is essential for bone tumors. Neutrophil gelatinase associated lipocalin (NGAL) and vitamin D have been found to be associated with cancer and may have potential to act as biomarkers for bone tumors also. METHODS: Serum levels of NGAL and 25-OH vitamin D were estimated in 14 patients with benign and 14 with malignant bone tumors and compared with 14 apparently healthy controls. The data collected was compared among different groups using appropriate statistical analysis. NGAL was estimated by enzyme linked immunosorbent as-say (ELISA) and 25-OH vitamin D by radioimmunoassay (RIA) in the serum samples. RESULTS: Serum NGAL levels were found to be increased significantly and 25-OH vitamin D levels decreased significantly in patients with malignant bone tumors as compared to healthy controls (p < 0.001) while this difference was not statistically significant in patients with benign bone tumors (p = 0.05). The difference in serum levels of NGAL and 25-OH vitamin D in patients with malignant bone tumors was found to be statistically significant as compared to patients with benign bone tumors (p < 0.05). The correlation was not statistically significant between the levels of 25-OH vitamin D and NGAL in group I (r = 0.067, p = 0.819), group II (r = 0.204, p = 0.483), and group III (r = -0.086, p = 0.772). CONCLUSIONS: Serum NGAL and 25-OH vitamin D may be used as important serological biomarkers in patients with bone tumors along with other standard investigative modalities.

Chemoradiation in Lung Cancer: Effect on Levels of NGAL and Vitamin D in Serum.

BACKGROUND: Mortality due to lung cancer is one of the growing concerns worldwide. Accurate and timely diagnosis is the key to treatment of this disease. Neutrophil gelatinase associated lipocalin (NGAL) and vitamin D have been found to be associated with cancer and may have potential to act as biomarkers for lung cancer. METHODS: Serum levels of NGAL and 25 hydroxy vitamin D (25OH vitamin D) were estimated in 25 patients with lung cancer before (Group I) and 4 weeks after standard treatment (Group II) by chemoradiation. The levels were also analyzed in 25 apparently healthy controls and data was compared among different groups using appropriate statistical analysis. NGAL was estimated by enzyme linked immunosorbent assay (ELISA) and 25OH vitamin D by radioimmunoassay (RIA) in the serum samples. RESULTS: Serum NGAL levels were found to be increased significantly in patients before treatment as compared to healthy controls (p < 0.001) while the levels decreased significantly after treatment (p < 0.01). The levels of vitamin D were found to be decreased in lung cancer patients as compared to healthy controls (p < 0.05) while after treatment the levels of vitamin D were found to be significantly increased (p < 0.001). The correlation was not statistically significant between the levels of vitamin D and NGAL in Group I (r = 0.12, p = 0.57), Group IIa (r = 0.037, p = 0.86), and Group IIb (r = 0.091, p = 0.66). CONCLUSIONS: Serum NGAL and vitamin D bear the potential to act as biomarkers in patients with lung cancer.

Alteration of ischemia modified albumin and nitric oxide levels in hypothyroidism.

BACKGROUND: Thyroid disorders especially hypothyroidism is associated with increased generation of oxidants. Nitric oxide and ischemia modified albumin are considered markers for oxidative stress. In addition, nitric oxide is involved in regulation of thyroid function and coagulation profile alteration in thyroid disorders may produce ischemia like conditions. METHODS: Nitric oxide and ischemia modified albumin were estimated in fifty patients of newly diagnosed hypothyroidism using standard photocolorimetric techniques. Results were compared with fifty healthy euthyroid controls and subjected to appropriate statistical analysis. RESULTS: Nitric oxide and ischemia modified albumin were found to be significantly raised (p < 0.05) in hypothyroid patients as compared to controls. A positive, but statistically insignificant correlation was observed between nitric oxide and ischemia modified albumin. CONCLUSIONS: Estmation of nitric oxide and ischemia modified albumin in hypothyroidism may help to throw light on its pathogenesis and assessing the severity of the disease, though further research is needed to establish their role as biomarkers in hypothyroidism.

Effect of imatinib on male reproductive hormones in BCR-ABL positive CML patients: A preliminary report.

Multiple animal studies, few clinical case reports and one study have observed decreased testosterone production and gynaecomastia as adverse effect of imatinib therapy. We have prospectively studied testosterone, LH and FSH levels at baseline and at 6 months of imatinib treatment in 34 newly diagnosed male BCR-ABL positive CML patients. While none of the patients had gynaecomastia at 6 months, the proportion of patients with low testosterone level increased significantly from 11.8% at baseline to 58.8% (p < 0.001) and those with high LH and FSH increased significantly from 26.4% and 23.5% to 82.4% and 76.4%, respectively (p < 0.001 and p < 0.001). Serum testosterone levels decreased significantly (p = 0.002) and serum LH and FSH levels increased significantly at 6 months of imatinib therapy (p = 0.001 and p = 0.003) in comparison to baseline levels. The findings document the effect of imatinib on testosterone levels in adult CML patients much before than reported earlier.

Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia.

Nitric oxide (NO) is involved in different stages of malignancies. Increased levels of NO have been reported in different leukemias. Imatinib is the preferred drug for the treatment of chronic myeloid leukemia (CML). Turmeric powder contains curcumin which has anti-leukemic property and also decreases NO synthesis. This study was conducted on fifty patients of CML divided into two groups, group A receiving imatinib alone and group B receiving turmeric powder along with imatinib for six weeks. Nitric oxide levels were estimated in these patients before and after receiving therapy and were analyzed statistically. Nitric oxide levels were found to be significantly decreased in both the groups, but more significantly in group B after receiving the respective treatments. Thus, curcumin acts as an adjuvant to imatinib in decreasing the NO levels and may help in the treatment of CML patients.

Diagnostic significance of adenosine deaminase, uric acid and C-reactive protein levels in patients of head and neck carcinoma.

BACKGROUND: Carcinomas are considered to be associated with increased cellular proliferation under antigenic stimulation and inflammation. Therefore, the markers of increased cellular turnover such as adenosine deaminase and uric acid were estimated quantitatively along with markers of inflammation such as C-reactive protein in squamous cell carcinoma of head and neck region. METHODS: The levels of adenosine deaminase, uric acid, and C-reactive protein were estimated in 50 patients of squamous cell carcinoma of head and neck region before starting any treatment and compared with their corresponding levels in 30 healthy age and gender matched controls. The patients were divided into four groups depending on their staging and their results were compared statistically and the coefficient of correlation was calculated using Pearson's formula. RESULTS: The levels of adenosine deaminase, uric acid, and C-reactive protein were found to be significantly higher in patients of head and neck cancers as compared to the levels in controls (p < 0.001). The levels were also observed to rise with staging. A positive correlation was observed between adenosine deaminase and uric acid (r = 0.743, p < 0.001), adenosine deaminase and C-reactive protein (r = 0.648, p < 0.001) and also between C-reactive protein and uric acid (r = 0.712, p < 0.001). CONCLUSIONS: Thus, estimation of adenosine deaminase, uric acid, and C-reactive protein can help in making the diagnosis and assessing the severity of disease in patients of head and neck carcinoma.

Chemoradiation in locally advanced Ca Cx: Effect on NGAL levels.

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to be unregulated in many cancers and to suppress tumor suppressor genes like p53 leading to cell proliferation. Studies to report its relationship with carcinoma cervix (Ca Cx) are still scant. MATERIALS AND METHODS: Serum NGAL levels were analyzed in 30 patients of histopathologically proven locally advanced Ca Cx at the time of diagnosis and 3 weeks after standard chemoradiation by enzyme-linked immunosorbent assay. These patients underwent either brachytherapy or supplementary external beam radiotherapy (EBRT) depending on the response of treatment. The results were analyzed statistically by applying Student's paired t-test. RESULTS: No statistically significant difference (P > 0.05) was observed in patients of Ca Cx before and after treatment or when compared stage wise, histopathological grade wise, or response wise. But the levels were found to increase when duration of treatment was ≥8 weeks (P = 0.040) and to decrease significantly when duration of treatment was <8 weeks (P = 0.0052). The NGAL levels also increased significantly after treatment in patients who received EBRT and supplementary radiotherapy (P = 0.019) while the pre- and post-treatment difference in NGAL levels was not statistically significant in patients who received EBRT + intracavitary brachytherapy (P > 0.05). CONCLUSION: As the duration as well as modality of treatment is quite important in Ca Cx, shorter duration associated with better results and lower NGAL levels, NGAL might prove to be a useful biomarker although further studies are needed to support the claim.

Comparison of Single Versus Multifraction Radiotherapy in Palliation of Painful Bone Metastases.

BACKGROUND: Bone is a common site of dissemination in advanced cancer accounting for one-third of all distant metastases. Various fractionation schedules of radiotherapy have been used for palliation of bone metastases. The aim of this study was to compare three schedules of external radiation therapy (8 Gy single session versus 20 Gy/5 fractions versus 30 Gy/10 fractions) for palliative management of bone metastases. METHODS: In the present study, 60 patients of bone metastases from any primary site were enrolled and randomly divided into three groups of 20 patients each by draw of lots. These patients received palliative external beam radiation therapy to the involved site. Patients were given 8 Gy single session, 20 Gy/5 fractions/1 week and 30 Gy/10 fractions/2 weeks in groups I, II and III, respectively. RESULTS: The percentage of patients with overall pain relief was 80% in group I, 75% in group II and 85% in group III (P = 0.7). The number of patients with complete pain relief was 4 (20%) in each group. Maximum patients got pain relief at 4 weeks post-radiotherapy. The number of patients with improved performance status was 4 (20%) in group II and 2 (10%) each in groups I and III (P = 0.5). Thirteen (65%) patients in each of the groups had decreased analgesic requirement at 2-month follow-up. Retreatment rate was more in the single fraction (20%) compared to only 5% in group II and none in the group III (P = 0.05). CONCLUSION: From the present study we conclude that 8 Gy single fraction is as effective as multifraction radiotherapy for the palliation of painful bone metastases. However, for a center like ours being the only Government Tertiary Cancer Care Centre in the State, general consensus drawn after this study, recommends external radiation therapy 20 Gy/5 fraction regimen to be an appropriate means of palliation of painful bone metastases.

Major Risk Factors in Head and Neck Cancer: A Retrospective Analysis of 12-Year Experiences.

BACKGROUND: Head and neck cancer (HNC) is the seventh most common type of cancer in the world and constitute 5% of the entire cancers worldwide. The global burden of HNC accounts for 650,000 new cases and 350,000 deaths worldwide every year and a major proportion of regional malignancies in India. More than 70% of squamous cell carcinoma of the head and neck are estimated to be avoidable by lifestyle changes, particularly by effective reduction of exposure to well-known risk factors such as tobacco smoking and alcohol drinking. METHODS: A retrospective analysis of 12 years (2001 - 2012) of HNC patients attending RCC, PGIMS Rohtak was done. Total numbers of cancer patients seen were 26,295 and out of these 9,950 patients were of HNCs, which were retrospectively analyzed for their associated risk factors in different HNC subtypes. Most of the patients, i.e. 92.3%, were presented as locally advanced HNC (stages III and IV). RESULTS: It has been observed that smoking and alcohol are the strongest independent risk factors responsible for increased risk of HNC and are further having synergetic correlations. CONCLUSION: The present study confirms the principal role of alcohol consumption and smoking in HNC carcinogenesis, as well as the differential associations with HNC subtypes, and a significant, positive, multiplicative interaction with different risk factors.

Levels of neutrophil gelatinase-assosciated lipocalin in patients with head and neck squamous cell carcinoma in Indian population from Haryana state.

AIM: To study the levels of neutrophil gelatinase associated lipocalin (NGAL) in head and neck squamous cell carcinoma (HNSCC). METHODS: This was a non randomized case control study conducted at Department of Biochemistry, in collaboration with Regional Cancer Center over a period of one year. The study population included 50 adult newly diagnosed HNSCC patients reporting in outpatient department at Regional Cancer Center and compared with 50 healthy controls. NGAL was estimated by ELISA technique. Student t test and χ2 test were applied for comparison of means of study groups. Correlations between groups were analyzed using Pearson correlation coefficient (r) formula. RESULTS: Patients with HNSCC exhibited significantly increased levels of NGAL (P < 0.05) as compared to healthy controls (978.88 ± 261.39 ng/mL vs 34.83 ± 7.59 ng/mL). Out of 50, 26 patients (52%) were in stage IV, 21 (42%) in stage III, 1 (2%) patient in stage II and 2 (4%) patients were in stage I. Metastasis was absent in 98% patients and mean NGAL levels were highest in these patients but P value was not significant. Mean NGAL levels were highest in stage IV [1041.54 ± 222.15 ng/mL (stage IV) vs 1040 ± 0.00 ng/mL (stage I); 900 ± 0.00 ng/mL (stage II) and 1031.90 ± 202.55 ng/mL (stage III)] and χ2 test was highly significant (P < 0.001). Thirty-six patients (72%) were having moderately differentiated HNSCC and mean NGAL levels were maximum in patients with well differentiated HNSCC (1164 ± 315.64 ng/mL vs 1013.33 ± 161.19 ng/mL in moderately differentiated and 890 ± 11.55 ng/mL in poorly differentiated) and the results were also highly significant (P < 0.001, χ2 test). CONCLUSION: The present work demonstrates a potential role of NGAL as cancer biomarker and its use in monitoring the HNSCC progression.

Comparative Evaluation of Three Palliative Radiotherapy Schedules in Locally Advanced Head and Neck Cancer.

BACKGROUND: The aim of the study was to evaluate and compare the efficacy, tolerability and toxicity of three palliative radiotherapy (RT) schedules in locally advanced head and neck carcinoma (LAHNC), i.e. Quad Shot schedule, Christie schedule and conventional palliative schedule. METHODS: The patients were randomly divided into three groups of 30 each. Group I patients were planned for 14.8 Gy in 4 fractions over 2 days, repeated three weekly for two more cycles. Group II patients were planned for 50 Gy in 16 fractions over 3.1 weeks. Group III patients were planned for 20 Gy in 5 fractions over 5 days, repeated after an interval of 3 weeks. The quality of life was assessed before and after RT using University of Washington Quality of Life questionnaire version 4. RESULTS: Local control rates were 84%, 76%, and 76% for groups I, II and III, respectively. Disease status at 6-month follow-up was no evidence of disease (20%, 28%, and 16%), residual disease (72%, 48%, and 76%), and recurrent disease (8%, 24%, and 8%) in groups I, II and III, respectively. Grade III acute skin reactions were 28%, 44%, and 16% in groups I, II and III, respectively. Grade III acute mucosal reactions were 36%, 56%, and 24% in group I, II and III, respectively. Quality of life improved in all groups after RT. CONCLUSION: Quad Shot schedule may be used in LAHNC with better local control and acceptable toxicity as compared to conventional palliative RT schedule in Indian setting.

Antioxidant status in neonatal jaundice before and after phototherapy.

Phototherapy has been related to increased oxidative stress and lipid peroxidation. In the present study, thirty full term jaundiced neonates with appropriate weight were analyzed before and after completion of phototherapy for malondialdehyde (MDA), reduced glutathione (GSH), total thiols, vitamin C and superoxide dismutase (SOD) levels in hemolysate and albumin levels in plasma. These parameters were analyzed in cord blood samples of 20 healthy neonates as control. It was observed that levels of MDA were elevated significantly (p<0.001) in patients as compared to controls and that the levels increased significantly after phototherapy (p<0.001). Levels of SOD were also found to be increased significantly as compared to controls and the levels rose after phototherapy (p<0.001). On the other hand, the levels of non-enzymatic antioxidants such as GSH, total thiols and vitamin C were significantly low (p<0.001) as compared to controls and the levels decreased significantly after phototherapy (p<0.001). The plasma albumin levels also were found to be decreased significantly after phototherapy (p<0.01). Therefore, phototherapy increases oxidative stress and should be used with care.

Updated overview of current biomarkers in head and neck carcinoma.

Squamous cell cancer is the most common type of malignancy arising from the epithelial cells of the head and neck region. Head and neck squamous cell carcinoma (HNSCC) is one of the predominant causes of cancer related casualties worldwide. Overall prognosis in this disease has improved to some extent with the advancements in therapeutic modalities but detection of primary tumor at its initial stage and prevention of relapse are the major targets to be achieved for further improvement in terms of survival rate of patients. Latest achievements in basic research regarding molecular characterization of the disease has helped in better perception of the molecular mechanisms involved in HNSCC progression and also in recognizing and targeting various molecular biomarkers associated with HNSCC. In the present article, we review the information regarding latest and potential biomarkers for the early detection of HNSCC. A detailed molecular characterization, ultimately, is likely to improve the development of new therapeutic strategies, potentially relevant to diagnosis and prognosis of head and neck cancers. The need for more accurate and timely disease prediction has generated enormous research interests in this field.

Chemotherapy: Impact on Anti-Müllerian Hormone Levels in Breast Carcinoma.

INTRODUCTION: Anti-Mullerian Hormone (AMH) is a glycoprotein of the transforming growth factor-ß (TGF-ß) family that seems to reflect the continuous non-cyclical growth of small follicles and can be considered an indirect index of the size of the resting primordial follicle pool. Accordingly, AMH represents a marker of Ovarian Reserve (OR) and is particularly useful in demonstrating ovarian tissue damage induced by chemotherapy. AIM: To evaluate and compare the levels of AMH in Breast Carcinoma patients before and after chemotherapy with age matched healthy controls and to assess whether AMH as a biochemical marker of the OR might improve prediction of chemotherapy related outcomes in these patients. MATERIALS AND METHODS: The present study was conducted in the Department of Biochemistry in collaboration with Department of Radiotherapy, Pt. B.D. Sharma, University of Health Sciences, Rohtak between June 2013 and June 2014. The subjects were divided into two groups. A total of 30 female patients of confirmed diagnosis of breast carcinoma were enrolled in the study group (Group I). The enrolled breast cancer cases were further divided into subgroups (Group-IA=Prechemotherapy & Group-IB= Postchemotherapy). Thirty healthy age matched female volunteers were enrolled as controls (Group II). Serum levels of AMH were determined by the ultrasensitive anti-müllerian hormone/ müllerian inhibiting substance (US AMH/MIS) Enzyme Linked Immuno Sorbent Assay (ELISA). RESULTS: There was a significant decrease in serum AMH levels in the both study group-IA and study group-IB as compared to control group-II (p<0.05 and p<0.001 respectively). The prechemotherapy (group-IA) serum AMH levels dropped significantly after chemotherapy (group-IB) (p<0.001). CONCLUSION: AMH levels declined after chemotherapy indicates direct chemotherapy induced damage to the granulosa cells and growing follicles, reflecting decrease ovarian reserve and fertility.

Exploring signet-ring cells in pregnant female.

INTRODUCTION: Primary signet-ring cell carcinoma (SRCC) of the colon and rectum are rare form, which present at an advanced stage and have poor prognosis. Different treatment policies of SRCC during different gestational age of pregnancy are explored from the literature. CASE STUDY: A 26-year-old young pregnant female with 10-week gestation presented with constipation and blood in stools and on per rectal examination a tender circumferential stricture was present 2 cm above the anal verge. Magnetic resonant imaging (MRI) pelvis of the patient revealed rectal thickening, the biopsy of which revealed characteristic appearance of "linitis plastica" and diagnosed as poorly differentiated adenocarcinoma with signet ring morphology with wide spread positivity for cytokeratin & p53. With this diagnosis, patient underwent medical termination of pregnancy (MTP). DISCUSSION: SRCC of the colon comprises about only 1% of all cases of colon cancer. When compared with other types of adenocarcinoma, patients with SRCC in the colon are younger and more likely to experience lymph node metastasis. Its incidence in pregnancy is estimated to be less than 0.1%. Certainly, any pregnant patient who reports rectal bleeding or has hemoccult positive stool on examination deserves careful evaluation to rule out cancer. The complex treatment of colorectal cancer in pregnancy is based on the gestational age of the fetus, tumor stage and need for emergent vs. elective management.

Nitric oxide and antioxidant status in head and neck carcinoma before and after radiotherapy.

OBJECTIVES: The mainstay of the treatment of head and neck squamous cell carcinoma (HNSCC) is radiotherapy, which acts by producing free radicals. Therefore, this study was planned to observe the effect of radiotherapy on oxidative stress in patients of HNSCC. METHODS: This study was conducted on 50 histopathologically proven cases of HNSCC. The levels of nitric oxide, glutathione-S-transferase, and vitamin C were estimated colorimetrically before and after treatment in patients and in 30 age- and sex-matched healthy controls. The results were compared statistically. RESULTS: The levels of nitric oxide and glutathione-S-transferase were significantly higher in patents as compared to controls and increased significantly after treatment. Vitamin C levels were significantly lower in patients as compared to controls and decreased significantly after treatment. CONCLUSIONS: HNSCC leads to increased oxidative stress and treatment in the form of radiotherapy itself produces an accentuation of this stress.

Giant neurilemmoma of the vagus nerve: a case report and review of literature.

Cervical vagal neurilemmomas are rare, usually asymptomatic, slow-growing tumours and defined as a benign, encapsulated neoplasm that arises in the nerve fibre. Magnetic resonant imaging (MRI) plays a central role in diagnosing vagal nerve neoplasm and in fact, provides important pre-operative information useful in planning optimal surgical treatment. A rare case of giant neurilemmoma is presented with a large swelling in the right side of the neck associated with breathlessness and paroxysmal cough. X-ray chest revealed large homogenous opacity in apical area of the right lung extending into the lower neck. MRI revealed a large 6 x 8 x 13 cm soft tissue, well defined mass with lobulated contours on the right side of the neck. The mass was pushing sternomastoid muscle anteriorly and carotid artery was pushed anteromedially. The mass was abutting the brachial plexus and compressing internal jugular vein. The mass was extending into the mediastinum up to the level of carina. The mass was also pushing the vessels in superior mediastinum towards left and was compressing the veins. Tumour was extending posterior to trachea and pushing trachea anteriorly and towards left and also compressing it. There was also erosion of adjacent anterior aspect of the right upper ribs. Subclavian artery was also encased by the mass. Multiple enlarged lymph nodes were seen in right cervical area. A provisional diagnosis of malignant schwannoma of right vagus nerve was made. Cytology from the fine needle aspirate of the right lower Cervical region of the swelling revealed features of neurilemmoma. Complete surgical resection is the treatment of choice with excellent prognosis, as the tumour was benign, and recurrence is nearly unknown, so it is possible and indeed recommended to preserve nerve integrity with careful dissection.

Effect of Ocimum sanctum on homocysteine levels and lipid profile in healthy rabbits.

CONTEXT: Ocimum sanctum has been reported to have a variety of medicinal properties. OBJECTIVE: The present study was planned to evaluate the effect of O. sanctum on plasma homocysteine levels and lipid profile in healthy rabbits. MATERIAL AND METHODS: Forty rabbits were divided into two groups (20 each). Group I rabbits received normal diet and group II rabbits received fresh leaves of O. sanctum (2 g/day) for 8 weeks along with normal diet. Fasting plasma samples were estimated for homocysteine and lipid profile. The results were analysed statistically. RESULTS: The levels of homocysteine, total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol were found to be decreased and high density lipoprotein cholesterol levels increased significantly on supplementation with O. sanctum (p < 0.001). DISCUSSION AND CONCLUSION: Thus, O. sanctum can prove to be a significant cardioprotective substance and an important adjuvant in the treatment of hyperhomocysteinemia and dyslipidemia.