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R Ganesan

Publications and source records attributed to R Ganesan.

At least 19 recordsLinked to original sources
PubMed2007

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.

Adult↗
PubMed2006

Aberrant termination triggers nonsense-mediated mRNA decay.

NMD (nonsense-mediated mRNA decay) is a cellular quality-control mechanism in which an otherwise stable mRNA is destabilized by the presence of a premature termination codon. We have defined the set of endogenous NMD substrates, demonstrated that they are available for NMD at every round of translation, and showed that premature termination and normal termination are not equivalent biochemical events. Premature termination is aberrant, and its NMD-stimulating defects can be reversed by the presence of tethered poly(A)-binding protein (Pab1p) or tethered eRF3 (eukaryotic release factor 3) (Sup35p). Thus NMD appears to be triggered by a ribosome's failure to terminate adjacent to a properly configured 3'-UTR (untranslated region), an event that may promote binding of the UPF/NMD factors to stimulate mRNA decapping.

3' Untranslated Regions↗
PubMed2005

MRI of vaginal conditions.

Magnetic resonance imaging (MRI) has become an important part of the assessment of suspected vaginal pathology. This pictorial review demonstrates the MRI features and some of the histopathological findings of a variety of vaginal conditions. These may be congenital (total vaginal agenesis, partial vaginal agenesis, longitudinal vaginal septum, transverse vaginal septum), benign (Bartholin's cyst, diffuse vaginal inflammation, invasive endometriosis, ureterovaginal fistula, post-surgical appearances with the formation of a neovagina and adhesions) or malignant, usually due to extension or recurrence from another pelvic malignancy. In this paper, examples of the above are described and illustrated together with examples of the much rarer primary vaginal malignancies.

Adenocarcinoma↗
PubMed2005

Mesonephric hyperplasia can cause abnormal cervical smears: report of three cases with review of literature.

BACKGROUND: Hyperplastic mesonephric remnants are an incidental finding in occasional uterine or cervical surgical specimens. We describe three cases in which such remnants were postulated to be the source of abnormal glandular cells in cervical smears. CASES: In all three cases abnormal glandular cells were seen in cervical smears. Subsequent histology showed the presence of hyperplastic mesonephric remnants that communicated with the endocervical canal and were likely to be the source of the abnormal glandular cells. We believe that the key features of these cells, which may aid their distinction from other causes of glandular abnormalities, are their loose clustering, lack of significant anisocytosis and cuboidal outlines. CONCLUSION: We aim to document mesonephric hyperplasia as a possible source for abnormal glandular cells in cervical smears.

Adult↗
PubMed2005

Superficial myofibroblastoma of the lower female genital tract: report of a series including tumours with a vulval location.

AIMS: To describe the clinical and pathological features of 12 further cases (in 11 patients) of superficial cervicovaginal myofibroblastomas (SCVM), rare tumours that hitherto have been described only in a single series of cases involving the cervix and vagina. METHODS AND RESULTS: The patients' ages ranged from 23 to 80 years. Ten tumours were located in the vagina and two in the vulva. Three patients had been taking tamoxifen. The tumours ranged in size from 2 to 45 mm and morphologically were well-circumscribed lesions composed of bland ovoid to spindle-shaped cells, often with wavy nuclei. These cells were arranged in a variety of architectural patterns and were set in a finely collagenous stroma. Five cases exhibited stromal oedema or myxoid change and in eight cases hyalinized areas with thick, dense collagen bundles were present. Immunohistochemically, there was positivity with vimentin (11 of 11 cases tested), CD34 (six of 12 cases), desmin (nine of 12 cases) and oestrogen receptor (nine of 11 cases). All cases tested were negative for smooth muscle actin, S100, h-caldesmon, HMB45, and CD31. In this study we expand on the morphological spectrum of these rare lesions and reiterate their association with tamoxifen. CONCLUSIONS: Since these lesions may occur on the vulva, as well as the cervix and vagina, we propose the term 'superficial myofibroblastoma of the lower female genital tract'.

Adult↗
PubMed2004

Cellular angiofibroma and related fibromatous lesions of the vulva: report of a series of cases with a morphological spectrum wider than previously described.

AIMS: Cellular angiofibroma (CA) is a rare benign mesenchymal lesion with a predilection for the vulval region. In this report we aim to describe the clinical, pathological and immunohistochemical features of a series of vulval mesenchymal lesions, some of which have the classically described histological appearance of CA while others exhibit atypical features. We believe these lesions fall within the broad spectrum of fibromatous lesions of the vulva. METHODS AND RESULTS: Seven cases were included. Histological sections were examined and immunohistochemical staining with vimentin, desmin, alpha smooth muscle actin, h-caldesmon, S100, EMA, AE1/3, CD34, CD10, ER, PR and MIB1 was performed. The patients' ages ranged from 20 to 65 years and the lesions ranged in size from 10 to 50 mm. All lesions were well circumscribed, moderately cellular lesions and were composed of bland spindle-shaped cells set in a fibrous stroma. Many blood vessels with thick hyalinized walls were present in four cases, in one case occasional such blood vessels were present and in two cases vessels with thick hyalinized walls were not present. In five cases the vessels were at least focally dilated resulting in a haemangiopericytomatous pattern. Histological features identified in a variable numbers of cases included peripheral adipose tissue (four cases), adipose tissue within the centre of the lesion (one case), stromal mast cells (six cases), stromal lymphoid aggregates (five cases), scattered multinucleate cells (five cases), hypocellular hyalinized areas (two cases), myxoid areas (four cases) and focal areas of marked cellular atypia reminiscent of symplastic change within a uterine leiomyoma (one case). Mitotic figures were identified in four cases, all with a mitotic count of < 1 per 10 high-power fields. Immunohistochemically all neoplasms were positive with vimentin and all but one with ER and PR (PR staining was not performed in one tumour). In all cases desmin, alpha smooth muscle actin, h-caldesmon, S100 and AE1/3 were negative (h-caldesmon and AE1/3 staining were not performed in one case). Three cases were positive with CD34, one with EMA and two with CD10. All exhibited a low MIB1 proliferation index of approximately 1%. One lesion recurred locally 6 months following initial removal. CONCLUSIONS: CA is a rare benign vulval mesenchymal lesion with limited potential for local recurrence. We describe several hitherto unreported histological features which add to the morphological spectrum. Although not all lesions exhibit the classically described histological features of CA, we believe all fall within the broad spectrum of benign vulval fibromatous lesions. These cases are characterized by vimentin positivity but negative staining with smooth muscle markers which assists in excluding many of the other vulvovaginal mesenchymal lesions which enter into the differential diagnosis. The immunophenotype indicates that CA probably exhibits fibroblastic rather than myofibroblastic differentiation. These lesions are almost always positive with ER and PR, suggesting that they probably arise from the hormone receptor-positive subepithelial mesenchymal layer within the lower female genital tract.

Adult↗
PubMed2004

CD40 expression in prostate cancer: a potential diagnostic and therapeutic molecule.

CD40, a member of the TNF receptor superfamily, is widely expressed on human immune cells. It is also frequently expressed on epithelial malignancies, suggesting that CD40 may contribute to the pathogenesis of some cancers. Activation of CD40 in cancer cells induces growth inhibition and sensitization to apoptotic stimuli. This study investigates CD40 expression in archival tissue from patients with prostate cancer. In all cases, normal prostatic acini expressed CD40, however, in 56 of 57 cases of prostate cancer no CD40 expression was detected. In the one other case, patchy CD40 expression was associated with prostatic in situ neoplasia. In conclusion, invasive prostate cancer is a CD40-negative tumour. These data may be relevant as a diagnostic tool; in providing insight into progression of cancer from normal epithelium; and in identifying novel therapeutic strategies for prostate cancer.

Aged↗
PubMed2004

Assessment of efficacy, safety and tolerability of fixed dose combination of telmisartan 40mg and hydrochlorothiazide 12.5mg in adult Indian patients with mild to moderate hypertension.

The objective of the study was to assess the efficacy, safety and tolerability of a fixed dose combination of telmisartan 40 mg and hydrochlorothiazide 12.5 mg in adult Indian patients with mild to moderate hypertension. A prospective, multicentric, open-label, non-comparative, phase IV study was conducted. A total of 353 patients of either sex, between 18- 65 years of age with supine blood pressure (BP) levels of systolic BP (SBP) of 140-200 mmHg and diastolic BP (DBP) of 95-114 mmHg were included. After a placebo run-in period of 2 weeks, each patient received a fixed dose combination of telmisartan/hydrochlorothiazide (40mg/12.5mg) once daily, for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety were assessed by physical examination, laboratory parameters and evaluation of adverse events. A total of 339 patients completed the study with 14 drop-out cases because of loss to follow-up. There was a significant fall (p<0.05) in both the SBP and DBP starting from the second week as compared to the baseline. Mean SBP had a significant reduction of 23.55 mmHg (15.0%) and 27.79 mmHg (18%) at the end of 6th and 8th week respectively, compared to baseline values. Mean DBP had also had a significant reduction of 12.51 mmHg (12.6%) and 15.17 mmHg (15.3%) at the end of 6th and 8th week respectively, compared to baseline values. This combination was well tolerated with only 3.9% of the total cases reporting mild adverse events like fatigue, dizziness, nausea, diarrhoea etc. The laboratory values were within normal limits. Fixed dose combination of telmisartan/hydrochlorothiazide (40 mg/12.5 mg) once daily has a significant therapeutic effect and a good tolerability profile in adult Indian patients with mild to moderate hypertension.

Adolescent↗
PubMed2003

Proapoptotic genes BAX and CD40L are predictors of survival in transitional cell carcinoma of the bladder.

The purpose of the study was to investigate the effects of expression of a range of genes involved in apoptosis on outcome in bladder cancer. Immunohistochemistry was used to examine expression of BCL2, BAX, P53, CD40 and CD40L in archival tissues of patients included in various treatment trials for transitional cell carcinoma (TCC) of the bladder. Data were collected on 94 patients who first presented with either invasive or superficial bladder cancer. Median follow-up for alive patients was 83 months (m) (range 12-195 m). Median survival was 80 m (95% CI=56-128 m). Median survivals for the various markers were as follows: BAX-positive patients 110 m vs BAX-negative patients 18 m (P=0.0002); CD40L-positive patients 95 m vs CD40L-negative patients 45 m (P=0.04); BCL2-positive patients 44 m and BCL2-negative patients 74 m, (P=0.64); CD40-positive patients 110 m and CD40 negative patients 45 m (P=0.12); and P53 positive patients 80 m and P53 negative patients 45 m (P=0.58). In conclusion, it was seen that overexpressions of BAX and CD40L are prognostic of better survival in TCC of the bladder. Our results also raise the possibility of the future development of CD40- and CD40 ligand-based immunotherapy for bladder cancer. This study links proapoptotic and antiapoptotic markers to overall survival.

Adult↗
PubMed2002

Efficacy and safety of nateglinide in the treatment of type II diabetes mellitus.

Nateglinide a new short-acting D-phenylalanine derivative represents a new chemical class of drugs for treating type 2 diabetes that is pharmacologically and therapeutically distinct from currently existing agents. Studies in normal patients and those with type 2 diabetes have shown that nateglinide reduces mealtime blood glucose excursions by physiologic regulation of insulin secretion. Nateglinide binds to and inhibits the K+(ATP) channel of the beta-cell, causing membrane depolarisation, with a subsequent influx of extracellular calcium that results in insulin secretion. A total of 105 patients in 5 centres with type II diabetes mellitus were taken according to the inclusion criteria and given drug treatment and were evaluated on their improvement in fasting and postprandial plasma glucose and glycosylated haemoglobin values for efficacy, besides physician's assessment of the overall safety and efficacy. Nateglinide in a dose of 60 mg before three main meals was given and increased to a maximum of 120 mg thrice daily over the first 3-4 weeks. Nateglinide had to be taken 10 minutes before meals. Duration of treatment was 12 weeks. The patients showed decrease in fasting plasma glucose from 2nd week onwards and reduction in glycosylated haemoglobin by 6th week onwards. Postprandial glucose reduction was also significant at the end of 12th week. The frequency of adverse effects was low and no serious adverse effects were encountered.

Blood Glucose↗
PubMed2000

Determination of enantiomers in a synthetic argininal peptide using capillary zone electrophoresis and high-performance liquid chromatography.

SCH 201781 is a synthetic argininal peptide containing two chiral centers and an aromatic sulfonamide group. It can exist as four reversible forms, the aldehyde, the hydrate, and two diastereomeric aminals. Capillary zone electrophoresis (CZE) and reversed-phase high-performance liquid chromatographic (HPLC) methods were developed to separate and quantitate the enantiomers in SCH 201781. Comparable results were obtained using both methods. The CZE method uses direct injection, while the HPLC method requires a precolumn derivatization and is more time consuming. The CZE method provides superior sensitivity to the HPLC method. Both methods were shown to be precise and reproducible.

Arginine↗
PubMed2000

Verrucous carcinoma arising in pseudoepitheliomatous keratotic and micaceous balanitis, without evidence of human papillomavirus.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is a condition which occurs on the glans penis of older men and may be associated with the development of a verrucous carcinoma. A role for human papillomavirus (HPV) in the aetiology of verrucous carcinoma has been implicated and several different HPV types have been found. We report a 74-year-old man who developed a verrucous carcinoma within an area of PKMB on the glans penis. Using a broad-spectrum polymerase chain reaction technique for identifying HPV, the epidermis of the area of PKMB and of the verrucous carcinoma were examined and no HPV DNA was identifiable. These results suggest that there is no part for HPV in the pathogenesis of PKMB or its transformation to verrucous carcinoma.

Aged↗
PubMed2000

Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy.

OBJECTIVE: To assess the prognostic significance of Bcl-2 expression on the clinical outcome after radiotherapy for muscle-invasive bladder cancer, and to determine if it is possible to identify a subgroup of patients to whom neoadjuvant chemotherapy can be targeted to improve survival. PATIENTS AND METHODS: Immunohistochemical staining for Bcl-2 and p53 was performed on the tumours of 51 patients with stage T2-T4a NXM0 transitional cell carcinoma of the bladder who had been included in a randomized clinical trial of radiotherapy with or without neoadjuvant cisplatin. The association between positive staining and salvage cystectomy rate and overall survival was examined, with a median follow-up of 12 years. RESULTS: Bcl-2 and p53 expression was positive in 31 (61%) and 39 (76%) of the tumours, with no association between either, or with tumour stage or grade. There was no difference according to Bcl-2 positivity in the salvage cystectomy rate (P = 0.83) or survival (P = 0.68) for the 51 patients as a whole, but Bcl-2-negative patients receiving neoadjuvant cisplatin had a significantly better prognosis, with a median survival of 72 months compared to 17 months in Bcl-2-positive patients, and a 5-year survival rate of 55% (P = 0.03). CONCLUSIONS: Quantifying Bcl-2 in patients undergoing radiotherapy for advanced bladder cancer identifies those who may benefit from neoadjuvant chemotherapy. Further studies of other members of the Bcl-2 family and other proteins controlling both cell proliferation and apoptosis are warranted, to define the roles and the interactions between them that may contribute to oncogenesis and resistance to standard treatments. This may allow the targeting of specific treatments to patients known to be sensitive to them, and aid the future development of novel therapies for bladder cancer.

Adult↗
PubMed2000

Vasculitis of the female genital tract with clinicopathologic correlation: a study of 46 cases with follow-up.

Forty-six cases of vasculitis affecting the female genital tract are described; only 41 similar cases have been previously reported, either as case reports or small series. The age range of the patients was from 22 to 80 years, and most of them presented with abnormal bleeding or were being treated conditions unrelated to the vasculitis. There were 39 hysterectomy specimens (26 of which were derived from total abdominal hysterectomies) and seven specimens of the cervix only. The vasculitis was confined to the cervix in 30 of the 46 cases; in 24 of these, the entire uterus was available for examination. In 23 cases, only a single vessel was involved, and in the other 23 there was more extensive vessel involvement. In all cases, the involved vessels were arterioles and small arteries. In 42 cases, the arteritis was of the polyarteritis nodosa (PAN) type, and in four, of the giant cell type (GCA). Follow-up ranged from < 1 year to 23 (mean, 3) years. Systemic manifestations were previously diagnosed or subsequently developed in only four patients, three with PAN and one with GCA; in each of them, the genital tract vasculitis was found only in the cervix (in one of these, however, the specimen was a loop excision of the cervix and the rest of the uterus was not assessable). The three patients with PAN subsequently developed extragenital PAN (one case), PAN and rheumatoid arthritis (one case), or PAN and polymyalgia rheumatica (one case). The patient with GCA had previously documented temporal arteritis and temperomandibular arthritis. The findings in this series and in previously reported cases indicate that vasculitis of the female genital tract is only rarely associated with systemic vasculitis.

Adult↗