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Biomedical subjects

A Mathew

Publications and source records attributed to A Mathew.

At least 19 recordsLinked to original sources
PubMed2003

Soft tissue sarcoma of the head and neck region in adults.

Soft tissue sarcomas (STS) are rare solid tumours accounting for less than 1% of all malignancies and are very unusual in the head and neck region. Histopathologically diagnosed cases of STS treated at Regional Cancer Centre (RCC). Trivandrum, India, between January 1989 and November 2000 were analyzed retrospectively. Survival analysis was carried out by Kaplan-Meier method and curves were compared using log rank test. A total of 22 cases were seen during the study period. The mean age of the patients was 36.4 years with male-to-female ratio of 2:1. The neck, lower jaw, tongue, cheek, scalp and maxilla were the commonest sites affected. None of the patients had palpable neck nodes or distant metastasis at presentation. All the patients were treated with primary surgical resection and this was followed by adjuvant treatment in 14 cases (63.6%). After a median follow-up of 14.5 months, two patients died, six developed local recurrence, four developed metastatic disease and another patient developed second primary sarcoma. The overall 5-year survival was 80% while the 5-year disease-free survival rate was 24.1%. The majority of the patients failed within first and second year. None of the parameters except grade of tumour (P=0.008) were found to have a significant effect on survival. The overall survival rate for patients with soft tissue sarcoma of the head and neck is good, however, disease-free survival is poor as the majority of these fail within 2 years of completing treatment.

Adolescent↗
PubMed2002

Primary malignant mucosal melanoma of the head and neck region: pooled analysis of 60 published cases from India and review of literature.

Malignant melanoma arising in the head and neck mucosa is a rare entity with incidence ranging from 2% to 10%. Because of the lack of data, the biological behaviour of these lesions still remains unpredictable and outcome dismal. We carried out a literature review for cases of mucosal melanoma of the head and neck reported from India and performed a pooled analysis on the available data. A total of 60 cases of head and neck melanomas were reported, of which 46 were in men. Palate and alveolus were the commonest sites. A total of 29 (48.3%) patients had regional node metastasis at presentation while five (12%) had distant metastasis. Three-year overall survival of 27.7% was observed. However, the disease-free survival rates at 3, 5 and 6 years were 39.4%, 39.4% and 13.1%, respectively. Metastasis at presentation and use of adjuvant radiotherapy were found to be the only significant predictors of survival. Malignant mucosal melanoma has aggressive biological behaviour and poor outcome. Radical surgery and adjuvant radiotherapy may provide a better local control and may help in improving survival.

Disease-Free Survival↗
PubMed2002

Global increases in kidney cancer incidence, 1973-1992.

Reports of increasing rates for kidney cancers in several count prompted this analysis of global incidence trends for total kidney cancers and by subsite. International incidence data for 5-year periods 1973-1977, 1978-1982, 1983-1987 and 1988-1992 were obtained from volumes IV to VII of Cancer Incidence in Five Continents published by the International Agency for Research on Cancer. The USA data for the same 5-year periods were obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Percentage changes in incidence rates were computed using the relative difference between the time periods 1973-1977 and 1988-1992, and annual percentage changes in incidence rates were computed using log linear regression. In 1988-1992, kidney cancer incidence rates (age-adjusted to the world-standard population) were highest in France (16.1/100,000 man-years and 7.3/100,000 woman-years) and lowest in India (2.0 and 0.9, respectively). Between 1973-1977 and 1988-1992, incidence rates rose among men and women in all regions and ethnic groups, with a few exceptions, mostly in Scandinavian countries. The largest percentage increase for men was in Japan (171%) and for women in Italy (107%). Rates for renal pelvis cancer were less than 1/100,000 person-years in almost all regions in both sexes, and the temporal trends were inconsistent. Incidence trends for renal parenchyma cancer tracked those for total kidney cancers, and appeared to result from increases in the prevalence of risk factors and in use of diagnostic imaging procedures.

Americas↗
PubMed2001

Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell lines in vitro and in vivo.

A bispecific monoclonal antibody (BsMAb) recognising carcinoembryonic antigen (CEA) and doxorubicin (Dox) was used in colorimetric microcytotoxicity assays with 3 human colon cancer cell lines (COLO320DM, SKCO1 and LS174T) showing no, high or medium CEA expression, respectively. The IC50 values for Dox with COLO320DM, SKCO1 and LS174T were 1,163, 28.5 and 324 ng/ml, respectively. BsMAb caused statistically significant reductions in Dox IC50 values at 1, 0.1 and 0.01 microg/ml with the CEA-expressing cell lines SKCO1 and LS174T but not with COLO320DM. BsMAb or control antibody alone had no significant effect on the cell viability of any of the cell lines and did not reduce Dox IC50 values. In vivo, there was a statistically significant inhibition of the growth of CEA-expressing LS174T cells growing as xenografts in nude mice treated with BsMAb and Dox compared to control mice. This effect was not seen with COLO320DM xenografts. Our results demonstrate that a BsMAb that recognises CEA and Dox can reduce the IC50 for Dox in vitro and inhibit growth in vivo in a CEA-specific manner.

Animals↗
PubMed2001

Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation.

Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the induction of allergic asthma, but the mechanisms regulating their recruitment into the airways are unknown. Signal transducer and activator of transcription factor (Stat)6 is a transcription factor essential for Th2 cell differentiation. Here we show that Stat6 also controls Th2 cell recruitment and effector function in allergic inflammation in vivo. To isolate the role of Stat6 in regulating Th2 cell trafficking and effector function from its role in Th2 cell differentiation, we used a murine model of asthma in which in vitro-differentiated Stat6(+/+) antigen-specific Th2 cells were adoptively transferred into naive Stat6(-/-) and Stat6(+/+) mice followed by aerosol antigen challenge. We found that all of the features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active chemokine production, and airway eosinophilia, mucus production, and hyperresponsiveness seen in Stat6(+/+) mice, were dramatically absent in Stat6(-/)- mice that received Stat6(+/)+ antigen-specific Th2 cells. Our findings establish Stat6 as essential for Th2 cell trafficking and effector function and suggest that interruption of Stat6 signaling in resident cells of the lung is a novel approach to asthma therapy.

Animals↗
PubMed2001

Affinity purification of novel bispecific antibodies recognising carcinoembryonic antigen and doxorubicin.

We have developed a method which combines Protein A affinity chromatography and HPLC analytical and semipreparative hydroxyapatite affinity chromatography to purify bispecific antibodies (BsMabs) from hybrid-hybridomas secreting antibodies recognising carcinoembryonic antigen (CEA) and the chemotherapeutic drug doxorubicin (Dox). Elution of the HPLC hydroxyapatite columns with a 60-360 mM phosphate buffer gradient was found to give better separation than elution with a 60-180 mM phosphate buffer gradient. Careful monitoring of HPLC fractions by enzyme linked immunosorbent assays for anti-CEA, anti-Dox and dual anti-CEA/anti-Dox activity, and pooling of fractions on the basis of these results, enabled the purification of novel BsMabs for use in in vitro and preclinical in vivo experiments.

Animals↗
PubMed2001

Cadherins as predictive markers of nodal metastasis in breast cancer.

Adhesion molecules, particularly cadherins play a pivotal role in cancer invasion and metastasis. Because the therapeutic management of tumors with and without nodal metastasis differs considerably, our idea was to identify tumors with metastatic potential. We studied the expression of E-cadherin and P-cadherin immunohistochemically in 51 cases of breast cancer that included 29 node-negative and 22 node-positive cases. Expression of the cadherins was mainly membranous, with cytoplasmic staining in a few lesions. Both E-cadherin and P-cadherin showed significant down-regulation of their expression in node-positive tumors in comparison to node-negative tumors. Logistic regression analysis revealed that the positive expression of E-cadherin and P-cadherin showed low odds ratios of 0.1 and 0.2, respectively, and were statistically significant. On multivariate analysis, both the cadherins were found to be of independent prognostic value. This suggests that cadherin expression could be a marker of nodal metastasis. An observation of interest was that the expression of E-cadherin and P-cadherin were highly correlated (correlation coefficient = 0.5873), which requires further evaluation for confirmation of a common regulatory pathway that could be activated in the early onset of nodal metastasis.

Adenocarcinoma↗
PubMed2001

Primary intraosseous carcinoma of the jaw: pooled analysis of world literature and report of two new cases.

Primary intraosseous carcinoma (PIOC) is a rare malignant neoplasm of the jaw. These tumours are believed to arise from the odontogenic epithelium and hence are also referred to as odontogenic carcinoma. A detailed search was made for squamous cell PIOC of the jaw in English literature using Medline Cancer CD. The data obtained were transferred onto dBase software. Two detailed case reports of patients treated at Regional Cancer Centre, Trivandrum during 1996 and 1997 were also included. A pooled analysis was carried out. Survival analysis was carried out using Kaplan-Meier method and log-rank statistics were used for comparing survival. A total of 35 cases were analysed, of which 33 were from published literature. The mean age of the patients at the time of diagnosis was 52.3 years with male to female ratio being 2.5:1. Posterior mandible was the predominant site. The median follow-up time was 28 months. Overall survival at 5 years was 37.8% (95% CI; 14.8-61.0) while the corresponding disease free survival was 29.8% (95% CI; 9.2-54.1). Primary intraosseous carcinoma is a rare tumour of jawbones, characterized by progressive swelling of the jaw, pain and loosening of tooth. The tumour is locally aggressive and metastasizes to regional nodes. The overall and disease free survival is poor with almost 50% patients failing loco-regionally within the first 2 years of follow-up.

Adult↗
PubMed2001

Stress-specific activation and repression of heat shock factors 1 and 2.

Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordinate the inducible regulation of heat shock genes in response to diverse signals. HSF1 is potent and activated rapidly though transiently by heat shock, whereas HSF2 is a less active transcriptional regulator but can retain its DNA binding properties for extended periods. Consequently, the differential activation of HSF1 and HSF2 by various stresses may be critical for cells to survive repeated and diverse stress challenges and to provide a mechanism for more precise regulation of heat shock gene expression. Here we show, using a novel DNA binding and detection assay, that HSF1 and HSF2 are coactivated to different levels in response to a range of conditions that cause cell stress. Above a low basal activity of both HSFs, heat shock preferentially activates HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132 coactivates both HSFs to different levels and hemin preferentially induces HSF2. Unexpectedly, we also found that heat shock has dramatic adverse effects on HSF2 that lead to its reversible inactivation coincident with relocalization from the nucleus. The reversible inactivation of HSF2 is specific to heat shock and does not occur with other stressors or in cells expressing high levels of heat shock proteins. These results reveal that HSF2 activity is negatively regulated by heat and suggest a role for heat shock proteins in the positive regulation of HSF2.

3T3 Cells↗
PubMed2001

Primary malignant chest wall tumours.

Neoplasms of the chest wall are not uncommon. Majority of the tumours occurring in the chest wall are benign. The tumours may arise from the soft tissues,connective tissues or bone. Metastatic tumours can arise as a result of direct infiltration or haematogenous spread. The management of these tumours is challenging. Resection of the chest wall with or without the excision of ribs, require reconstruction not only for aesthetic reasons but also for providing the stability to the chest wall which is of prime importance in maintaining the respiratory functions. In this article, 46 cases of the primary malignant chest wall tumours seen over a period of 5 years are reviewed.

Adolescent↗
PubMed2000

Transient decreases in human T cell proliferative responses following vaccinia immunization.

To further study the immunosuppression associated with virus infections, we analyzed the proliferative responses of serial PBMC samples obtained following vaccinia virus immunization. In four of five volunteers, responses to PHA, anti-CD3, vaccinia virus, and recall antigens were markedly decreased at at least one time point between days 5 and 29 after vaccination. Responses to PHA were restored by the addition of IL-2 or irradiated autologous healthy PBMC in the two volunteers tested, suggesting that the proliferation defect is attributable to accessory cell dysfunction. In one donor, immobilized anti-CD3 failed to induce proliferation, but addition of immobilized anti-CD28 partially restored proliferation. These results indicate that vaccinia virus infection can transiently suppress proliferative responses of PBMC, in part by causing accessory cell dysfunction. Our findings extend the list of viral infections associated with systemic immunologic effects and demonstrate that suppression of proliferation can occur with localized virus infections.

Antibodies↗
PubMed2000

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Adolescent↗
PubMed2000

Metastatic prostate cancer (with prostate-specific antigen of 9996) presenting as obstructive jaundice.

A 78-year-old man admitted with clinical jaundice and pelvic pain had a total bilirubin level of 6.56 mg/dL, an alkaline phosphatase level of 855 U/L, and a prostate specific antigen (PSA) level of 9996 ng/mL. A computed tomogram demonstrated marked retroperitoneal, peripancreatic, periceliac, and periaortic lymphadenopathy. A bone scan revealed increased radiolabeled technetium uptake in the pelvis, vertebral column, parietooccipital region, ribs, and appendiceal skeleton. A biopsy of one pelvic lesion revealed metastatic prostate cancer. This man's obstructive jaundice and bone pain had a dramatic response to treatment with a gonadotropin-releasing hormone analog (leupro lide) and antiandrogen (bicalutamide). All bone pair and clinical signs of jaundice disappeared in 1 week His total bilirubin decreased to 0.84 mg/dL by 2 weeks His PSA values reflected this clinical response, decreasing to 4022 ng/mL in 1 week, 2680 ng/dL after 2 weeks and 1028 ng/mL after 1 month of the above therapy.

Aged↗
PubMed2000

Risk factors for pre-cancerous lesions of the cervix.

Studies on risk factors for pre-cancerous lesions of the uterine cervix have shown strong association with sexual practice. Women with multiple sexual partners and intercourse at early age are at high risk. A role of male partners in further enhancing the risk has been identified. All these support the hypothesis relating to a sexually transmissible aetiological agent. An extensive review of the literature on the risk factors for pre-cancerous lesions of cervix has been carried out. The risk factors were grouped into genital, sexual, chemical, dietary and life factors. Human papilloma virus (HPV) is the major infectious aetiological agent associated with the development of pre-cancerous lesions of cervix. Other co-factors such as multiple sexual partners of the male as well as the female and early age of first intercourse are also involved at the critical aetiological step of progression from low-grade to high-grade lesions. The role of other infectious agents in terms of supportive or interactive effects is not clear. No independent effect for herpes simplex virus 2 on risk is observed. Other risk factors include cigarette smoking, oral contraceptive usage, certain nutritional deficiencies and poor personal hygiene. However, it is not clear whether these factors operate independently from HPV. There is no consistency in the independent effect of these factors on the development of low- to high-grade lesions of cervix. There is a similarity in the patterns of risk between pre-cancerous lesions of the cervix and cervical cancer. Monogamy, late commencement of sexual activity, personal hygiene and use of barrier contraceptive methods help towards primary prevention. In the long-term, primary prevention of cervical neoplasia through HPV immunization of population may be a possibility.

Coitus↗
PubMed2000

Diet and stomach cancer: a case-control study in South India.

A prospective case-control study was conducted in Trivandrum, India, to evaluate the dietary risk factors for stomach cancer. One hundred and ninety-four patients with stomach cancer registered at the Regional Cancer Centre (RCC), Trivandrum, Kerala, India, during the period 1988-1991 were considered as cases. A minimum of one control (n = 305), matched for age (+/- 5 years), sex, religion and residential area was selected from the visitors to RCC during the same period. Interviews were carried out using a predetermined structured food frequency questionnaire. The information collected also included socio-demographic/economic background, tobacco chewing, tobacco smoking and alcohol habits. Data were analysed using a multiple logistic regression model. Odds ratios for all dietary variables were estimated. Increased risks were observed with higher consumption of rice (OR 3.9; 95% CI 1.6-10.0). Risk was high for those consuming spicy food (OR 2.3; 95% CI 1.1-5.0), high consumption of chilli (OR 7.4; 95% CI 4.0-13.5) and consumption of high-temperature food (OR 7.0; 95% CI 3.7-12.9). On multivariate analysis, high consumption of rice, high consumption of chilli and consumption of high-temperature food were found to be independent risk factors.

Adult↗