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P B Desai

Publications and source records attributed to P B Desai.

At least 19 recordsLinked to original sources
PubMed2003

In vitro and in vivo percutaneous absorption of catechol.

The Cosmetic Ingredient Review Expert Panel found insufficient data to conclude that catechol could be used safely in permanent hair dye products. Information was lacking on the extent of oxidation and skin absorption of remaining catechol. In vitro percutaneous absorption studies were conducted in human and rat skin using a consumer permanent hair dye spiked with 0.6% catechol. A 30-min application demonstrated 0.4% of the applied dose was absorbed through human skin and 0.2% through rat skin. The minimal absorption observed was due to the short exposure time and to partial oxidation of catechol by the dye developer. The fate of catechol remaining in rat skin after exposure in vitro and in vivo was investigated with additional absorption studies using catechol in ethanol. At 72 h, 24-h application of 4% catechol resulted in skin absorption of 81% of the applied dose in vitro and 53% in vivo. Skin levels measured at 24 h remained unchanged after 72 h. Therefore the skin reservoir did not contribute to the estimated systemic absorption. A deconvolution technique employed to predict skin absorption using plasma levels from intravenous and dermal administration overestimated in vivo skin absorption due to volatility of catechol in an ethanolic vehicle.

Administration, Cutaneous↗
PubMed2001

Increased activity of CYP3A enzyme in primary cultures of rat hepatocytes treated with docetaxel: comparative evaluation with paclitaxel.

PURPOSE: Docetaxel, a potent antimicrotubule agent widely used in the treatment of ovarian, breast and lung cancer, is extensively metabolized in various animal species, including humans. The metabolism of docetaxel to its primary metabolite, hydroxydocetaxel, is mediated by cytochrome P450 isozymes CYP3A2 and CYP3A4 in rats and humans, respectively. Several substrates of enzymes belonging to the CYP3A subfamily are known to induce different CYP isozymes, including CYP3A enzymes. Recently, paclitaxel, a compound structurally related to docetaxel, has been shown to significantly elevate the expression of CYP3A in rat and human hepatocytes. In this study we investigated the influence of docetaxel, employed at clinically relevant concentrations, on the level and the activity of cytochrome P450 3A in primary cultures of rat hepatocytes. METHODS: Rat hepatocytes were treated with different concentrations of docetaxel, paclitaxel and other CYP3A inducers. Testosterone 6beta-hydroxylase activity of intact hepatocytes was used as a marker for CYP3A. The immunoreactive CYP3A levels in the S-9 fractions were determined by Western blot analysis. RESULTS: We observed that by day 3 of drug treatment, docetaxel at concentration in the range of 2.5-10 microM increased the CYP3A enzymatic activity and the immunoreactive CYP3A levels in a concentration-dependent manner. At the 10 microM level, docetaxel caused a twofold increase in the CYP3A activity and a threefold increase in the immunoreactive CYP3A levels. However, the docetaxel-mediated CYP3A activity and enzyme level increase were significantly lower than those mediated by paclitaxel and dexamethasone. A comparison of the testosterone 6beta-hydroxylation activity in hepatocytes treated with these agents at a concentration of 5 microM each yielded the following rank order of induction capacity: dexamethasone > paclitaxel > docetaxel (15-fold, 5-fold, 2.2-fold, respectively). CONCLUSIONS: Taken together, our findings raise the possibility that docetaxel at clinically relevant concentrations increases CYP3A activity. The potential for docetaxel-mediated changes in the metabolism of other coadministered drugs and its own metabolism, in relation to that due to paclitaxel, are discussed.

Animals↗
PubMed1999

The quality of swallowing for patients with operable esophageal carcinoma: a randomized trial comparing surgery with radiotherapy.

BACKGROUND: Surgery is considered the standard treatment for operable esophageal carcinoma, although there is no compelling evidence that surgery can achieve better results than radiotherapy. There has previously been no direct randomized comparison of these two modalities with survival or disease specific outcome end points. METHODS: Ninety-nine patients with operable squamous cell carcinoma of the esophagus were randomly allocated to surgery or radiotherapy after stratification for tumor length (< or = or >5 cm). Those randomized to surgery underwent transthoracic esophagectomy with limited lymphadenectomy, whereas those in the radiotherapy arm received 50 gray in 28 fractions followed by a 15-gray boost to the primary tumor. Disease specific outcome was assessed for 4 subgroups: 1) disease specific symptoms, 2) physical symptoms, 3) ability to work, and 4) social/family interaction and global perception of disease specific outcome. The questionnaire was given prior to treatment and posttreatment at 3-month intervals for 1 year. Death was a secondary end point. RESULTS: There was an overall improvement in the quality of swallowing in both treatment arms after treatment and with the passage of time. The swallowing status was better in the surgery arm than in the radiotherapy arm at 6 months after treatment (P = 0.03, Fisher's exact test). Logistic regression analysis showed randomization arm (P = 0.035), time since treatment (P = 0.003), and pretreatment swallowing status to be significant determinants of posttreatment swallowing status. Surgery was twice as likely to result in improvement in swallowing than radiotherapy after correction for time and pretreatment swallowing status. Overall survival was better in the surgery arm than in the radiotherapy arm (P = 0.002, log rank test) (OR = 2.74 with 95% confidence intervals 1.51-4.98; P < 0.009, Cox proportional hazards model). CONCLUSIONS: Both surgery and radiotherapy can improve the quality of swallowing significantly for patients with operable esophageal carcinoma. Surgery is marginally superior to radiotherapy in improving the quality of swallowing. In this trial, survival in the surgery arm was significantly better than in the radiotherapy arm, although the small number of patients is a limitation.

Carcinoma, Squamous Cell↗
PubMed1999

Alcohol as an additional risk factor in laryngopharyngeal cancer in Mumbai--a case-control study.

A retrospective case-control study of 1698 male pharyngeal and laryngeal cancers seen at the Tata Memorial Hospital, Mumbai from 1980 to 1984 was undertaken to assess the association between the cancers and chewing, smoking, and alcohol habits. Male controls were chosen from persons who attended the hospital during the same period and who were diagnosed as free from cancer, benign tumor, and infectious disease. Statistical analysis was based on unconditional logistic regression method. Bidi smoking and alcohol drinking emerged as significant factors for pharyngeal and laryngeal cancers. Illiterates had 50 to 60% excess risk for pharyngeal cancer only. Nonvegetarian diet did not emerge as significant factor in our study.

Adult↗
PubMed1998

Benign metastasizing chondroblastoma: a case report.

BACKGROUND: Metastasis of histologically benign chondroblastoma is a rare event. The authors report a new case, 12th in the literature, wherein multiple lung metastases appeared almost simultaneously with the primary lesion in the right talus bone. METHODS: A histologic evaluation of the primary lesion in the talus and the pulmonary metastasis was performed, and an ultrastructural study of the latter was done. Published literature on metastasizing chondroblastoma was reviewed to identify any consistency in the pattern and the outcome. RESULTS: Metastasis of chondroblastoma is uncommon but well known. Although radiologic and histologic aggressive features have been sought, they do not necessarily correlate with the outcome. CONCLUSIONS: Metastasis in chondroblastoma has been insufficiently stressed in the literature, unlike metastasis in giant cell tumors. The purpose of this case report is not only to document this uncommon event (the 12th case of lung metastasis) but also to emphasize that patients with chondroblastoma may have metastasis at presentation. Hence, all patients need to be evaluated regularly from the onset for possible lung metastasis so that deposits can be detected early for total resection.

Adult↗
PubMed1998

Risk assessment of tobacco, alcohol and diet in cancers of base tongue and oral tongue--a case control study.

This is a retrospective case-control study of male tongue cancer patients seen at Tata memorial Hospital, Bombay, during the years 1980-84. The purpose of the study was to identify the association of tobacco, alcohol, diet and literacy status with respect to cancers of two sub sites of tongue namely anterior portion of the tongue (AT) (ICD 1411-1414) and base of the tongue (BT) (ICD 1410). There were 142 male AT patients and 495 BT patients interviewed during the period. 635 interviewed male patients who were free of any disease were considered as control. Bidi smoking was found to be a significant risk factor for BT patients and tobacco chewing for AT patients respectively. Alcohol drinkers showed about 45% to 79% excess risk for both sites of tongue cancer. Illiteracy and non vegetarian diet proved to be a significant factor for AT patients only. The study brings out that the location of cancer has got a direct bearing with the type of tobacco use and other related habits and this inturn may provide meaningful interpretation of variations observed in the incidence of tongue cancer around the world.

Adult↗
PubMed1997

Historical control bias: adjuvant chemotherapy in esophageal cancer.

UNLABELLED: Conclusion based on historical controls are known to be fallible in assessing efficacy of treatment due to selection bias. Historical controls have been repeatedly used in investigating efficacy of newer treatment avenues in esophageal cancer. The aim of the study was to assess the efficacy of adjuvant chemotherapy in esophageal cancer after correction for an historical control bias. PATIENTS AND METHODS: The database of 433 patients treated surgically for cancer of the esophagus at our institute between 1980 and 1989 was analyzed. The analysis was carried out using the Cox model for known prognostic factors without any correction for historical bias. Database was reanalysed after introducing registration year as a variable in the model to correct for historical control bias, which was further examined by carrying out a case-control study comparing chemotherapy (n = 83) vs contemporary control (n = 164) matched for lymph-node status, age and sex randomly selected from the same database. RESULTS: The analysis without correction for historical control bias showed lymph-node metastasis (P = 0.000), female sex (P = 0.002), depth of invasion (P = 0.001) and adjuvant chemotherapy (P = 0.03) as significant predictors of survival. On introduction of registration year as a variable, lymph-node metastasis, sex and depth of invasion continued to be significant factors but chemotherapy was replaced by registration year (P = 0.02). The database with contemporary control showed lymph-node metastasis (P = 0.000), depth of invasion (P = 0.008) and female sex (P = 0.001) as significant factors. Chemotherapy had no effect on survival. CONCLUSION: Results from historical controls are unreliable in detecting modest treatment benefits. Adjuvant chemotherapy in esophageal cancer should be tested within the tenets of randomized controlled trials with adequate-sample size to ascertain its efficacy.

Age Factors↗
PubMed1997

Reversal of doxorubicin resistance in multidrug resistant melanoma cells in vitro and in vivo by dipyridamole.

The occurrence of multidrug resistance (MDR) decreases the clinical utility of several anticancer agents, including doxorubicin (DOX). A transmembrane efflux pump, P-glycoprotein (P-gp), is frequently implicated in the development of MDR in tumor cells. Dipyridamole (DP), a clinically used antiplatelet drug, enhances the cytotoxicity of the anticancer drugs affected by MDR. Although this aspect has been studied extensively in cell culture models, the effectiveness of DP to overcome multidrug resistance has not been investigated using in vivo models of multidrug-resistant solid tumors. Therefore, the objective of this study was to evaluate the role of DP in the reversal of resistance to DOX in tumor-bearing mice in the context of its anti-MDR activity in vitro. For this purpose, drug-sensitive murine melanoma cells (B16V) and their DOX-selected MDR variant, B16VDXR cells, were used. In vitro, the reversal of DOX resistance of B16VDXR cells by DP was determined using clonogenic assays, and the influence of DP on the transport of DOX was evaluated by measurement of steady-state accumulation as well as efflux of DOX in B16VDXR cells. Antitumor activity of different treatments was assessed by monitoring tumor growth. Pharmacokinetics of DOX, with or without DP, were evaluated in C57BL/6 mice bearing B16V or B16VDXR tumors. DP produced a 6.4-fold reversal of resistance to DOX in vitro; this was accompanied by an increase (3.6-fold) in the steady-state intracellular accumulation of DOX and a marked reduction in the efflux of DOX from B16VDXR cells. Furthermore, a linear correlation was observed between the EC50 values and the steady-state intracellular levels of DOX in the multidrug-resistant cells. In the in vivo experiments, similar growth patterns were seen for the DOX alone and the DOX+DP groups for B16V tumors. The results with B16VDXR tumors were in sharp contrast. The DOX+DP treatment caused a significant delay in the growth of B16VDXR tumors compared to treatment with DOX alone or controls. DP did not alter the plasma pharmacokinetics of DOX in C57BL/6 mice but resulted in a significant increase in the intratumoral accumulation of DOX.

Animals↗
PubMed1997

A clinicopathologic profile of adrenocortical tumors.

OBJECTIVE: To study the clinical, biochemical, hormonal, radiological and histopathological profile of adrenocortical tumors in children; to assess the clinicopathological correlations and note the future outcome. DESIGN: Retrospective and prospective study. SETTING: Hospital based; Endocrine Service of our institution and other institution based services. SUBJECTS: 14 children (Females = 11, Males = 3) with adrenocortical tumor, aged 8 months to 13 years (mean age 5.1 +/- 3.42 years), seen over a period of 9 years. RESULTS: Females predominated (F:M = 3.7:1). Majority (64%) had a mixed picture with cushingoid features and virilization, whereas 36% presented only for virilization. Elevated serum cortisol levels with loss of diurnal variation was noted only in those with mixed clinical presentation. Adrenal androgen elevation was noted in majority of cases as virilization was common to all. CT confirmed the diagnosis of tumor, 7 on either side. Thirteen cases were operated. Histopathologic diagnosis was carcinoma in 7 and adenoma in 6 cases. Three of the seven with carcinoma died within 3 months to 2 years but two of these with small tumours (weight 60-65 g and diameter < 6 cm) were well at 2 and 5 years, while as one of the six with a large adenoma had recurrence and metastasis after three years. CONCLUSION: Female preponderance was marked (4 times), 43% of tumors had occurred by 3 years of age and 64% by 6 years. Neither the hormonal parameters nor the histopathology correlated well with the biological behavior and outcome. Prolonged and vigilant follow up is essential.

Adolescent↗
PubMed1996

Primary carcinoid tumor of the liver: report of four resected cases including one with gastrin production.

Four cases of primary hepatic carcinoid were identified during a retrospective study of liver resections for primary tumor. The cases included two adult males, one adult female, and a 9-year-old boy in whom gastrin levels were documented. The estimation of gastrin levels was prompted by symptoms suggestive of acid-peptic disease. One patient died postoperatively. The other three are alive and well at 3 years, 2 years, and at 1 year, respectively, after surgery, outcomes distinctly different from hepatocellular carcinomas. Diagnostic difficulties may be experienced in histologic assessment, and this may require recourse to immunohistochemistry and electron microscopy. Long-term follow-up and careful exclusion of a possible primary elsewhere are necessary for establishing the primary nature of liver carcinoids.

Adult↗
PubMed1996

Intrathoracic anastomosis after oesophageal resection for cancer.

Cervical anastomosis has been advocated to avoid the pulmonary complications and life-threatening anastomotic disruptions following intrathoracic oesophagogastric anastomosis. This is a retrospective review of 111 oesophageal resections followed by an intrathoracic anastomosis. These resections were performed between September 1993 and August 1994 within a residency training program. The left thoracoabdominal approach was used for distal tumours and the Ivor Lewis technique for more proximal tumours. Squamous cell carcinoma accounted for 72% patients (n = 80), adenocarcinoma for 25% (n = 28), and others for 2.7% patients (n = 3). Of the patients, 69% had pathologic Stage III tumours. Operative mortality rate was 1.8% (two patients). Perioperative complications occurred in 39 patients, including anastomotic leak in 10 patients and myocardial infarction in 2 patients. In the absence of a leak, there were no major pulmonary complications requiring intensive care or ventilatory support. Of those patients with anastomotic disruption, 80% were salvaged by early clinical diagnosis and appropriate treatment. We conclude that transthoracic oesophagectomy with an intrathoracic anastomosis is a safe procedure that can be performed with low mortality and acceptable morbidity.

Adenocarcinoma↗
PubMed1996

Chemotherapy for carcinoma of the esophagus: a comparison of evidence from meta-analyses of randomized trials and of historical control studies.

BACKGROUND: Chemotherapy (CT) has been used as an adjunct to local treatment (surgery or radiotherapy) in esophageal carcinoma. A meta-analysis of all published randomized clinical trials and historical control studies which have used cisplatinum-based combination CT was carried out to asses the effect of chemotherapy on survival for esophageal cancer. MATERIALS AND METHODS: A computer-based literature search was performed for the period from January 1988 to March 1995 using the index terms "Esophageal neoplasms' and "Chemotherapy'. The frame of reference was further narrowed to include only cisplatinum-based combination chemotherapy. Twelve randomized clinical trials (RCT) and eight historical control (HC) studies were included in the meta-analysis. RESULTS: In the overview of HC studies a highly significant reduction in odds of death with CT was observed (68% +/- 8% OR = 0.32, 95% CI 0.24-0.42). On the other hand, the overview of RCTs showed a relative reduction in odds of death for the CT group of 4.2% +/- 23.7% (OR = 0.96, 95% CI 0.75-1.22). CONCLUSIONS: There was a gross overestimation of treatment effect in the studies using HC as compared to RCTs, despite the use of cisplatinum-based chemotherapy in both groups. The meta-analysis of RCTs reveal no significant survival benefit from cisplatinum-based adjuvant/neoadjuvant chemotherapy in esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Epidemiological observations on cancer of the oesophagus--a review of Indian studies.

This is an epidemiological review on cancer of the oesophagus. In this attempt, all aspects of epidemiological factors based on national and international studies on oesophageal cancer have been brought out. The problem of this cancer in Indian context has been documented. The association of tobacco and alcohol habits with oesophageal cancer has been confirmed from the studies conducted in India. There is an urgent need to educate the common people about the harmful effect of these two habits and governments and voluntary organisation should take effective steps for its prevention.

Esophageal Neoplasms↗
PubMed1996

Cancer control in the Asia Pacific region--the next lap.

Cancer control in any part of the world has to be a multi-directional effort addressed in a holistic manner. The general impression that cancer control means only collation of epidemiological data and efforts at primary prevention needs to be redefined because preventive and educative oncology, though an important component of cancer control, can achieve long-term goals only after 20 years or more. Along with such long-term objectives, methodology needs to be developed which takes care of immediate and recent needs in early diagnosis, effective treatment, and appropriate basic research for the ultimate control and cure of cancer. A holistic approach to the cancer control effort will, therefore, need the combined skills of many different specialists.

Asia↗
PubMed1995

Effect of tamoxifen on mitoxantrone cytotoxicity in drug-sensitive and multidrug-resistant MCF-7 cells.

The influence of the antiestrogen tamoxifen (TAM) on the activity of mitoxantrone (MXN), was evaluated against wild-type MCF-7/WT and their multidrug-resistant variant MCF-7/ADR cells. Multidrug resistance (MDR) in this cell line which was selected for resistance to Adriamycin (ADR), is associated with increased expression of P-glycoprotein (P-gp). In a clonogenic assay it was observed that TAM (1-10 microM) significantly enhanced the activity of MXN in the MCF-7/ADR but not in the drug-sensitive cell line. Isobologram analysis indicated that the effect of the combination was additive in the parental MCF-7/WT cells and strongly synergistic in the MDR MCF-7/ADR cells. Also, TAM (10 microM) caused a three-fold increase in the steady-state levels (Css) of MXN in MCF-7/ADR cells but did not modulate MXN levels in MCF-7/WT cells. The observed synergism in MCF-7/ADR cells was perhaps due to the increase in Css of MXN that may involve interaction of TAM with P-gp. The combination of MXN and TAM may be useful in the treatment of drug-sensitive and drug-resistant breast cancer.

Breast Neoplasms↗
PubMed1995

Combination therapy with 5-fluorouracil and L-canavanine: in vitro and in vivo studies.

L-Canavanine (CAV) is a potent L-arginine antagonist, produced by legumes such as the jack bean, Canavalia ensiformis. CAV is cytotoxic to MIA PaCa-2 human pancreatic cancer cells. We sought to determine whether CAV's efficacy as an anticancer agent might be increased in combination with 5-fluorouracil (5-FU), a pyrimidine antimetabolite with activity against solid tumors. Using optimal conditions for the expression of CAV's cytotoxicity against MIA PaCa-2 cells, CAV was more cytotoxic to the cells than 5-FU. The combination of both drugs at a fixed molar ratio of 1:1 exhibited synergistic effects in the cells as determined by combination index analysis. The combination of 5-FU:CAV was tested at a ratio of 5:1 and exhibited antagonism at lower effect levels, additivity at 50% effect levels and slight synergism at higher effect levels. A 10:1 combination of both drugs (5-FU:CAV) exhibited antagonistic effects at all levels. When the drugs were combined at a molar ratio of 20:1, increased antagonism was observed. When CAV (1.0 or 2.0 g/kg daily) and/or 5-FU (35 mg/kg daily) was administered to colonic tumor-bearing rats for five consecutive days, the antitumor activity of the drug combination was significantly greater than the combined effects of either drug alone. However, the body weight loss experienced by CAV-treated rats was increased in those rats exposed to a combination of both drugs. These studies using different tumors provide in vitro and in vivo evidence that combination therapy offers a viable means of improving CAV's intrinsic efficacy while decreasing the concentration of 5-FU required to produce the same cytotoxic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pediatric germ cell tumor. An experience with BEP.

PURPOSE: This study is an analysis of our experience with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs). PATIENTS AND METHODS: The study included all children (age < 16 years) who were registered between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT and received BEP chemotherapy. In addition to the clinicopathological features, the response rate, survival rate, and toxicity were analyzed. RESULTS: There was a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was the most common type (62%). Tumor markers were increased in 89% (50 of 56). Complete responses were observed in 89.1% (49 of 55) and partial responses in 10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83% and progression free survival was 93%. Median follow-up was 18 months. Median survival is not yet reached. The chemotherapy was well tolerated. CONCLUSIONS: From the present report, it is apparent that BEP chemotherapy is very effective and well tolerated in children with GCT. The data probably suggests that conservative surgery, when combined with effective chemotherapy, can result in cure of the majority of children with GCTs.

Adolescent↗