Association of genetic and epigenetic modification in MTHFR gene with coronary artery disease patients in North Indian population

Background: Methylene tetra hydro folate reductase (MTHFR) gene polymorphism C677T (rs180113) and DNA methylation in promoter region of MTHFR gene may contribute to the development of coronary artery disease however the results have been inconsistent across studies with different populations, so the aim of our study is to explore the association of polymorphism in MTHFR gene and methylation in promoter region with coronary artery disease (CAD) and other risk factor (lipid profile, homocysteine, vitamin B12 and folic acid levels)  leading to CAD in of north Indian population. Methods: Total 100 CAD patients and 100 healthy controls were enrolled in the study. Genotyping of rs1801133 SNP (C677T) is done by PCR-RFLP and DNA methylation study in promoter region by methylation specific PCR. Lipid profile analysis by automated chemistry analyzers, serum homocysteine, folic acid and vitamin B12 was assayed by ELISA. Results: As per our finding the T allele (OR=3.03, 95% CI=1.74-5.27) and hyper methylation in promoter region of MTHFR increases the odds of coronary artery disease, (OR=3.05, 95% CI=1.7-5.6). Study participants with CT and TT genotype had significantly higher homocysteine (Hcy) (p=0.001), lower folic acid level (p=0.0), and HDL levels (p<0.0001) than those with CC genotype. The study subjects with hyper methylated promoter region have a significantly high homocystenemia levels (p=0.001). Conclusions: The TT genotype of the MTHFR C677T gene polymorphism and hyper methylation in promoter region of MTHFR, is associated with CAD and can be useful in identification of new biomarkers, development of preventive and therapeutic strategies for CAD.

Metastatic sweat gland adenocarcinoma: A clinico-pathological dilemma

BACKGROUND: Sweat gland adenocarcinoma is a rare malignancy with high metastatic potential seen more commonly in later years of life. Scalp is the most common site of occurrence and it usually spreads to lymph nodes. Liver, lung and bones are the distant sites of metastasis with fatal results. The differentiation between apocrine and eccrine metastatic sweat gland carcinoma is often difficult. The criteria's are inadequate to be of any practical utility. CASE REPORT: Two cases of metastatic sweat gland adenocarcinoma (one of eccrine and the other one of apocrine origin) are being reported on account of the rarity and different outcome. CONCLUSION: Sweat gland carcinomas are rare cancers with a poor prognosis often presenting as histological surprises. Surgery in the form of wide local excision and lymph node dissection is the mainstay of treatment. Chemotherapy and/or radiotherapy has limited role

Pleomorphic Sarcoma of Breast: A Report of Two Cases and Review of Literature

Sarcomas account for less than 1% of all primary breast malignancies, pleomorphic sarcoma of the breast being even rarer. We present two cases of pleomorphic sarcoma of the breast in a 35-year-old and a 43-year-old female. An extensive review of the available literature with evaluation of the etiology, changing terminologies and histopathologic features of pleomorphic sarcoma of the breast are discussed. The prognostic factors and treatment modalities have also been reviewed

Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India-A cross-sectional study

BACKGROUND: Breast cancer is the second most common malignancy among women, next to cervix cancer. Understanding its pathogenesis, morphological features and various risk-factors, including family history holds a great promise for the treatment, early detection and prevention of this cancer. PATIENTS AND METHODS: In an attempt to evaluate the clinico-morphological patterns of breast cancer patients, including their family history of breast and/or other cancers, a detailed analysis of 569 breast cancer cases diagnosed during the years 1989–2003 was carried out. Mean and standard deviation and Odds ratios along with 95% confidence intervals were estimated. χ(2)/Fisher's exact test were employed to test for proportions. RESULTS: Mean age of the patient at presentation was 47.8 years, ranging from 13–82 years. Among the various histo-morphological types, Infiltrating duct carcinoma (IDC) was found to be commonest type i.e. in 502 cases (88.2%), followed by infiltrating lobular carcinoma (ILC) in 21 cases (3.7%) and other types forming 9(1%). Out of 369 cases where TNM staging was available, stage IIIB (35.2%) was the commonest. Lymph node positivity was observed in 296 cases (80.2%). Out of 226 cases evaluated for presence of family history, 47 cases (20.7%) revealed positive family history of cancer, among which breast or ovarian cancer were the commonest type (72.0%). Patients below 45 years of age had more frequent occurrence of family history as compared to above 45 years. Amongst familial cases, Infiltrating duct carcinoma was the commonest form accounting for 68.8% cases while ILC was found to be in a higher proportion (12.5%) as compared to non- familial cases (5.4%). CONCLUSION: Among the various determining factors for development of breast cancer and for its early detection, family history of cancer forms one of the major risk factor. It is important to take an appropriate history for eliciting information pertaining to occurrence of cancers amongst the patients' relatives there by identifying the high risk group. Educating the population about the risk factors would be helpful in early detection of breast cancer

BATSE spectroscopy analysis system

The Burst and Transient Source Experiment (BATSE) Spectroscopy Analysis System (BSAS) is the software system which is the primary tool for the analysis of spectral data from BATSE. As such, Guest Investigators and the community as a whole need to know its basic properties and characteristics. Described here are the characteristics of the BATSE spectroscopy detectors and the BSAS

Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer-a prospective clinical study

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an integral part of multi-modality approach in the management of locally advanced breast cancer. It is vital to predict response to chemotherapy in order to tailor the regime for a particular patient. The prediction would help in avoiding the toxicity induced by an ineffective chemotherapeutic regime in a non-responder and would also help in the planning of an alternate regime. Development of resistance to chemotherapeutic agents is a major problem and one of the mechanisms considered responsible is the expression of 170-k Da membrane glycoprotein (usually referred to as p-170 or p-glycoprotein), which is encoded by multidrug resistance (MDR1) gene. This glycoprotein acts as an energy dependent pump, which actively extrudes certain families of chemotherapeutic agents from the cells. The expression of p-glycoprotein at initial presentation has been found to be associated with refractoriness to chemotherapy and a poor outcome. Against this background a prospective study was conducted using C219 mouse monoclonal antibody specific for p-glycoprotein to ascertain whether pretreatment detection of p-glycoprotein expression could be utilized as a reliable predictor of response to neoadjuvant chemotherapy in patients with breast cancer. PATIENTS AND METHODS: Fifty cases of locally advanced breast cancer were subjected to trucut(® )biopsy and the tissue samples were evaluated immunohistochemically for p-glycoprotein expression and ER, PR status. The response to neoadjuvant chemotherapy was assessed clinically and by using ultrasound after three cycles of FAC regime (cyclophosphamide 600 mg/m(2), Adriamycin 50 mg/m(2), 5-fluorourail 600 mg/m(2 )at an interval of three weeks). The clinical response was correlated with both the pre and post chemotherapy p-glycoprotein expression. Descriptive studies were performed with SPSS version 10. The significance of correlation between tumor response and p-glycoprotein expression was determined with chi square test. RESULTS: A significant relationship was found between the pretreatment p-glycoprotein expression and clinical response. The positive p-glycoprotein expression was associated with poor clinical response rates. When the clinical response was correlated with p-glycoprotein expression, a statistically significant negative correlation was observed between the clinical response and p- glycoprotein expression (p < 0.05). There was another significant observation in terms of development of post NACT p-glycoprotein positivity. Before initiation of NACT, 26 patients (52%) were p-glycoprotein positive and after three cycles of NACT, the positivity increased to 73.5% patients. CONCLUSION: The study concluded that pretreatment p-glycoprotein expression predicts and indicates a poor clinical response to NACT. Patients with positive p-glycoprotein expression before initiation of NACT were found to be poor responders. Thus pretreatment detection of p-glycoprotein expression may be utilized, as a reliable predictor of response to NACT in patients with breast cancer The chemotherapy induced p-glycoprotein positivity observed in the study could possibly explain the phenomenon of acquired chemoresistance and may also serve as an intermediate end point in evaluating drug response particularly if the adjuvant therapy is planned with the same regime

Isolated colostomy site recurrence in rectal cancer-two cases with review of literature

<p>Abstract</p> <p>Background</p> <p>Colostomy site carcinomas are rare with only eight cases reported in the world literature. Various etiological factors like adenoma-cancer sequence, bile acids, recurrent and persistent physical damage at the colostomy site by faecal matter due to associated stomal stenosis have been considered responsible. Two such cases are being reported and in both cases there was no evidence of any local recurrence in the pelvis or liver and distant metastasis. Both patients had received adjuvant chemotherapy following surgery.</p> <p>Case presentation</p> <p>First case was a 30-year-old male that had reported with large bowel obstruction due to an obstructing ulcero-proliferative growth (poorly differentiated adenocarcinoma) at the colostomy site after abdomino-perineal resection, performed for low rectal cancer six years previously. Wide local excision with microscopically free margins was performed with a satisfactory outcome. Four years later he presented with massive malignant ascites, cachexia and multiple liver metastasis and succumbed to his disease.</p> <p>Second case was a 47-year-old male that presented with acute large bowel obstruction due to an annular growth (well differentiated adenocarcinoma) in the upper rectum. He was managed by Hartmann's operation and the sigmoid colostomy was closed six months later. Five years following closure of colostomy, he presented with two parietal masses at the previous colostomy site scar, which, on fine needle aspiration cytology were found to be well-differentiated adenocarcinomas of colorectal type. Surgery in the form of wide local resection with free margins was performed. He presented again after five years with recurrence along the previous surgery scar and an incisional hernia and was managed by wide local excision along with hernioplasty. Follow-up of nine years following first surgery is satisfactory.</p> <p>Conclusion</p> <p>Colostomy site/scar recurrence of rectal carcinoma is rare and could be due to various etiological factors, although the exact causative mechanism is not known. Surgery with microscopically free margins is recommended in the absence of metastatic disease. Stenosis of the stoma is considered as one of the most important contributory factors and should be followed carefully.</p

CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription

Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity