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Biomedical subjects

H S Pandha

Publications and source records attributed to H S Pandha.

At least 19 recordsLinked to original sources
PubMed2005

An interleukin-10 promoter polymorphism may influence tumor development in renal cell carcinoma.

PURPOSE: Polymorphisms in the promoter of the interleukin-10 (IL-10) gene may influence tumor development by altering the levels of IL-10 present in the serum or tumor microenvironment. In this study we looked for evidence of specific polymorphisms of the IL-10 promoter and whether lymphocyte expression of IL-10 correlates with specific genotypes. MATERIALS AND METHODS: Archival, paraffin embedded renal cell carcinoma tissue from 166 patients and 161 controls were genotyped for the IL-10-1082 single nucleotide polymorphism using real-time polymerase chain reaction. IL-10 protein expression in peripheral blood lymphocytes was assessed by standard enzyme-linked immunoassay in 32 patients with renal cancer. RESULTS: Patient-to-control comparisons identified the AA genotype to be significantly greater in patients with renal cell carcinoma (44% vs 30%, p <0.05). However, study of IL-10 protein expression in peripheral blood lymphocytes from patients with renal cancer showed no statistical difference in IL-10 expression among the GG, AA or AG genotypes. CONCLUSIONS: We found that there was a significantly larger proportion of patients with renal cell carcinoma with the AA homozygous genotype than in a normal population cohort. This result is in accordance with those in previous studies of prostate cancer and cutaneous malignant melanoma. In contrast to previous studies of other tumor types, no correlation could be established between IL-10-1082 polymorphism and serum IL-10.

Adult↗
PubMed2004

Signet ring cell carcinoma in the prostate.

Metastases to the prostate gland are rare and often found in the context of widespread metastatic disease. We report an unusual case of primary gastric signet ring cell adenocarcinoma (SRCC) diagnosed over 1 year after treatment for metastatic disease in the prostate.

Aged↗
PubMed2003

Coxsackie B and adenovirus receptor, integrin and major histocompatibility complex class I expression in human prostate cancer cell lines: implications for gene therapy strategies.

Gene therapy strategies based on modifying tumour cells using high efficiency adenoviral vectors have shown promise in the clinic. Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain. Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies. We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression. These findings, together with the demonstration of appreciable levels of cell-surface expression of integrins, suggest that cancer vaccine strategies based on modifying whole prostate cancer cells should be feasible using the current generation of recombinant adenoviral vectors, without deleterious effects on either the virus vector or the target cell.

Adenoviridae↗
PubMed2000

Oncological applications of gene therapy.

Despite the rapid technological advances that continue to sustain the field of cancer gene therapy, few individual patients have benefited from the revolution so far. The plethora of clinical trials described confirms that each malignancy will have its own ideal strategy based on the associated molecular defects, and there has been rapid progress from this viewpoint. At the same time, there has been a renewed appreciation for the limitations to gene therapy, which include low efficiency of gene transfer, poor specificity of response and methods to accurately evaluate responses, and lack of truly tumor-specific targets at which to aim. As with all new therapies, we are climbing a steep learning curve in terms encountering treatment-related toxicities, as well as profound ethical and regulatory issues.

Animals↗
PubMed2000

Gene therapy: recent progress in the clinical oncology arena.

Despite the rapid technological advances that continue to sustain the field of cancer gene therapy, few individual patients have benefited from the revolution so far. The plethora of clinical trials described confirms that each malignancy will have its own ideal strategy based on the associated molecular defects, and there has been rapid progress from this viewpoint. At the same time, there has been a renewed appreciation for the limitations to gene therapy, which include low efficiency of gene transfer, poor specificity of response and methods to accurately evaluate responses, and lack of truly tumor-specific targets at which to aim. As with all new therapies, we are climbing a steep learning curve in terms encountering treatment-related toxicities, as well as profound ethical and regulatory issues.

Animals↗
PubMed1999

Genetic prodrug activation therapy for breast cancer: A phase I clinical trial of erbB-2-directed suicide gene expression.

PURPOSE: This trial was designed to test the safety and efficacy of a tumor-specific genetic prodrug activation therapy targeted by use of the human erbB-2 gene promoter. The erbB-2 oncogene is overexpressed in approximately 20% of cases of breast cancer and is associated with poor prognosis. PATIENTS AND METHODS: Twelve breast cancer patients received transcriptionally targeted gene therapy in a phase I clinical trial using direct intratumoral injection of plasmid construct combined with systemic administration of prodrug. The genetic prodrug activation therapy is specifically targeted to erbB-2-overexpressing breast cancer cells by use of a therapeutic cassette that contains the Escherichia coli cytosine deaminase gene driven by the tumor-specific erbB-2 promoter, thus allowing activation of fluorocytosine to the active cytotoxic fluorouracil only within tumor cells that express the oncogene. RESULTS: The approach was shown to be safe and to result in targeted gene expression in up to 90% of cases. Using a number of different assays, we demonstrated that significant levels of expression of the suicide gene were specifically restricted to erbB-2-positive tumor cells, confirming the selectivity of the approach. CONCLUSION: The results of this study, the first targeted gene therapy for breast cancer and the first to use the cytosine deaminase system in human subjects, are encouraging for the development of genetic prodrug activation therapies that exploit the transcriptional profile of cancer cells.

Adult↗
PubMed1999

Metastatic extramedullary plasmacytoma of the lung.

Extramedullary plasmacytomas (EMP) comprise 4% of all plasma cell neoplasms and commonly in the upper airway or digestive tract but rarely develop in the lungs. We present a case of primary pulmonary plasmacytoma in an 89 year old man, presented as a hilar mass with associated intrathoracic and extrathoracic lymph node metastases, but without evidence of myeloma. Treatment options for EMP include surgery, surgery and radiotherapy, surgery and chemotherapy or chemotherapy alone. Local recurrence rate is reported as 10-30%, with 17-48% progressing to multiple myeloma and median survival being 63-101 months. In view of the advanced age of this patient, who was initially treated unsuccessfully with intravenous cyclophosphamide and subsequently with two cycles of VAMP chemotherapy with good resolution of his disease, he is undergoing regular follow-up only.

Aged↗
PubMed1996

Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c-erbB2 and c-erbB3 in bladder cancer.

Expression of the c-erbB3 protein was determined in transitional cell carcinoma of the bladder by immunohistochemistry. Strong membrane staining was observed in 10 per cent of cases (7/70) and cytoplasmic and membrane overexpression in 20 per cent (14/70). Overexpression of the epidermal growth factor (EGF) receptor (36 per cent, 25/70) and c-erbB2 proteins (9 per cent 6/70) was determined in the same series of cases. c-erbB3 overexpression was positively correlated with EGF receptor expression (P < 0.025) but appeared to be inversely associated with c-erbB2 overexpression.

Biomarkers, Tumor↗
PubMed1996

Sacral chordoma, gas gangrene and bilateral renal cell carcinomas.

The case history is reported of a 59-year-old man with a locally symptomatic sacral chordoma. During treatment with radical radiotherapy, he developed gas gangrene, which proved rapidly fatal. At post-mortem examination there was evidence of local invasion of the rectum by the tumour and extensive gangrenous myonecrosis (gas gangrene) involving the pelvic tissues and left leg. An unexpected finding was the presence of histologically distinct bilateral renal cell carcinomas. Neither gas gangrene nor renal cell cancer has been reported previously in association with sacral chordoma.

Carcinoma, Renal Cell↗
PubMed1996

Octreotide in malignant intestinal obstruction.

Octreotide has proved an effective agent in the palliation of refractory malignant intestinal obstruction. This may be achieved through a pro-absorptive effect on the small bowel mucosa, an effect on improving gastrointestinal motility, by a reduction in gastrointestinal hormone levels and by a direct anti-neoplastic effect on the obstructing tumour. The simple route of administration of octreotide and the paucity of side effects reported in two recent studies should make the physician consider its use in this particularly distressing complication of advanced cancer.

Animals↗
PubMed1995

Risk factors for pneumothorax during percutaneous Hickman line insertion in patients with solid and haematological tumours.

The purpose of this study was to identify risk factors for pneumothorax during percutaneous subclavian Hickman line insertion in patients with haematological (HT) or solid tumours (ST). One hundred and twelve patients (55 HT, 57 ST) had 132 subclavian Hickman lines inserted under fluoroscopic control. Lines were inserted on the left on 116 occasions and the right in 16. Thirty-five single, 29 double and 68 triple lumen catheters were inserted. Variables included in the analysis were age, sex, side of insertion, catheter gauge and nutritional status as indicated by the body mass index (BMI kg/m2). Both univariate and logistic regression analyses were performed. There were ten pneumothoraces, all occurring in patients with STs. Univariate analysis revealed that patients with STs were older (median age 59 versus 36 years; P = 0.0001) and more cachectic (median BMI 21.9 versus 24.2 kg/m2; P = 0.03) than those with HTs, and the patients experiencing pneumothorax were older (median age 57 versus 44 years; P < 0.01) and more cachectic (median BMI 19.6 versus 24.0 kg/m2; P = 0.004) than those undergoing uncomplicated procedures. For patients with a BMI < 19 kg/m2 versus those with a BMI > 19 kg/m2, the pneumothorax rate was 5/8 versus 5/124 (P < 0.00001). Logistic regression analysis confirmed the significantly older age of the patients with STs (P < 0.001) and of those experiencing pneumothorax (P = 0.02). This analysis also confirmed the lower BMI of patients experiencing pneumothorax (P = 0.002). The patients' sex, the side of line insertion and the catheter gauge were not associated with pneumothorax on either the univariate or logistic regression analyses. From these data we conclude that pneumothorax complicating a subclavian Hickman line is significantly more likely in elderly patients with a low BMI. Such patients are more likely to have STs than HTs. In patients with a BMI < 19 kg/m2, the subclavian route should be used with caution.

Adult↗