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D Mazhar

Publications and source records attributed to D Mazhar.

12 recordsLinked to original sources

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

Adult↗

COX inhibitors and breast cancer.

There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Preclinical evidence favours an antitumour role for COX inhibitors in breast cancer. However, the epidemiological evidence for an association is conflicting. Trials are being conducted to study the use of COX inhibitors alone and in combination with other agents in the chemoprevention of breast cancer, and in the neo-adjuvant, adjuvant, and metastatic treatment settings. In evaluating the potential use of these agents particularly in cancer chemoprophylaxis, the safety profile is as important as their efficacy. Concern over the cardiovascular safety of both selective and nonselective COX-inhibitors has recently been highlighted.

Breast Neoplasms↗

The presentation and survival of patients with non-cutaneous AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immune deficiency syndrome related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe for the first time a proportion of patients with AIDS-KS who presented with no evidence of cutaneous disease. PATIENTS AND METHODS: From our cohort of 5932 individuals infected with the human immunodeficiency virus (HIV-1) treated in the HAART era, 319 were identified with KS. Of these, 11 patients (5.4%) were diagnosed with KS without the presence of any cutaneous disease. We compared their survival, clinical, immunological and virological characteristics to other individuals with KS. RESULTS: There were no statistically significant differences in survival, CD4 count or HIV viral load at KS presentation. We observed that tumour-associated oedema (P = 0.046) and non-oral gastrointestinal KS (P = 0.042) were significantly more common in patients with non-cutaneous KS. Only one case of non-cutaneous KS was observed prior to the era of highly active anti-retroviral therapy (HAART). CONCLUSIONS: Non-cutaneous KS is a recognisable condition; patients should be treated with the standard of care as their prognosis is not inferior. This is likely to reflect a strong immune response, in the era of HAART.

Acquired Immunodeficiency Syndrome↗

Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Animals↗

COX and cancer.

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Animals↗

Managing metastatic prostate cancer.

Prostate cancer is one of the most commonly diagnosed malignancies in the west. Most patients with metastatic or recurrent prostate cancer initially respond to androgen deprivation therapy, but almost all eventually progress. This review will focus on current treatment options for metastatic prostate cancer, with a focus on hormonal therapies, chemotherapy and treatment of bony disease, along with biological and targeted therapy.

Androgen Antagonists↗

Diet and prostate cancer.

There are four mini-reviews in this section, all on different areas of urological interest. Diet and prostate cancer continues to offer areas of clinical and laboratory research for investigation. Not every urologist looks after patients with spinal cord injury, but neuropathic bladder problems caused by other conditions are common. One of the acute conditions in these patients is autonomic dysreflexia, and this is covered here. I am about to introduce a series of papers which will form a consensus on the management of genitourinary trauma, which appears elsewhere in the journal. In this section this month, authors from Germany describe the diagnosis and treatment of male genital injuries. Finally, the concept that the urologists who operate on the largest volume of cases have the best outcomes from a particular operation is examined.

Diet↗

Prostate cancer.

It is a paradigm in cancer treatment that early detection and treatment improves survival. However, although screening measures lead to a higher rate of detection, for small bulk localised prostate cancer it remains unclear whether early detection and early treatment will lead to an overall decrease in mortality. The management options include surveillance, radiotherapy, and radical prostatectomy but there is no evidence base to evaluate the benefits of each approach. Advanced prostate cancer is managed by hormonal therapy. There have been major changes in treatment over the last two decades with the use of more humane treatment and developments in both chemotherapy and radiation. In this article we review the natural history and management of prostate cancer.

Humans↗