Search PubMed⌕ Search

Biomedical subjects

M Bains

Publications and source records attributed to M Bains.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neoadjuvant therapy of esophageal cancer.

Locally advanced esophageal cancer, potentially curable with surgery or radiotherapy-based treatment, has a poor prognosis because of the eventual development of systemic metastatic disease in the majority of patients. Local recurrence of disease after local treatment modalities is equally problematic. The use of systemic chemotherapy in the surgical and radiation-based treatment of esophageal cancer is reviewed, including the approach of preoperative chemotherapy, preoperative concurrent chemotherapy plus radiotherapy, and chemoradiotherapy as definitive treatment without surgery. The use of chemoradiotherapy has clearly been shown to be superior to radiotherapy alone in the nonsurgical management of locoregional esophageal cancer. Recent trials suggest that preoperative chemoradiotherapy may be superior to surgery alone but trials are ongoing to better define the role of combined modality therapy in the surgical management of esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A phase II trial of paclitaxel and cisplatin in patients with locally advanced metastatic esophageal cancer: a preliminary report.

We demonstrated in an earlier trial that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has substantial antineoplastic activity, with acceptable toxicity, in patients with advanced metastatic esophageal cancer. Preclinical and clinical data from studies in other tumors indicate substantial additive or even synergistic activity for paclitaxel/cisplatin combination chemotherapy. We encountered substantial toxicity with a cisplatin/paclitaxel/5-fluorouracil combination. To maximize paclitaxel dose, we initiated a phase II trial using cisplatin and paclitaxel alone. This report summarizes preliminary data from that trial. Paclitaxel 200 mg/m2 is given as a continuous, 24-hour infusion on day 1. On day 2, cisplatin 75 mg/m2 is given. Courses are repeated every 21 days. Dose adjustments are based on myelosuppression, neurotoxicity, and (for cisplatin) renal or auditory toxicity. All patients receive recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary end point of the study is tumor regression. Secondary end points include duration of response and toxicity. Two groups of patients are being studied. Those with advanced metastatic disease receive chemotherapy alone as palliative treatment. The second group has locoregional disease that is potentially resectable. These patients receive combined-modality therapy involving induction paclitaxel/cisplatin chemotherapy followed by surgery. To date, 37 evaluable patients have been treated. Twenty had advanced metastatic disease and 17 were treated before planned surgery. Twenty-seven patients had adenocarcinoma and 10 had epidermoid carcinoma. Major objective responses were seen in 49% of all patients, with similar response rates for patients with metastatic and locoregional disease. The median duration of response for patients with metastases is 4+ months. Among 14 patients treated before surgery, one experienced a complete pathologic response, and the neoplasms of 43% were downstaged. Primary toxicity was neutropenia, which was tolerable. Surgical morbidity or mortality did not increase. Cisplatin plus paclitaxel is an active combination in the treatment of patients with advanced or locoregional esophageal cancer. Further studies with this combination both in metastatic and locally advanced disease are indicated.

Adult↗
PubMed1992

Role of Pseudomonas aeruginosa outer membrane protein OprH in polymyxin and gentamicin resistance: isolation of an OprH-deficient mutant by gene replacement techniques.

The cloned oprH gene of Pseudomonas aeruginosa was mutated by inserting a 1.4-kbp fragment that encodes tetracycline resistance. This mutated gene was then incorporated into the P. aeruginosa chromosome by homologous recombination. Growth of the resultant oprH::tet mutant in Mg(2+)-deficient medium had little effect on susceptibility to polymyxin B, gentamicin, or EDTA unless the mutant was complemented by the cloned oprH gene in plasmid pGB25. In contrast, growth of the parent strain on Mg(2+)-deficient medium resulted in resistance to all three agents. These data support the hypothesis that overexpression of OprH under Mg(2+)-deficient growth conditions is conditionally required for resistance to these three agents.

Bacterial Outer Membrane Proteins↗
PubMed1992

A pleiotropic, posttherapy, enoxacin-resistant mutant of Pseudomonas aeruginosa.

An enoxacin-resistant Pseudomonas aeruginosa mutant (G49) isolated during patient therapy was characterized in detail. The G49 mutant was cross resistant to several classes of antibiotics including quinolones, beta-lactams, chloramphenicol, and tetracycline, but not imipenem or aminoglycosides. Compared with its paired pretherapy isolate G48, this mutant had several alterations in outer membrane proteins including a complete loss of the major porin protein OprF and a substantially altered lipopolysaccharide profile. Revertants were selected at a frequency of approximately 1% after enrichment for OprF+ cells on low-salt proteose peptone no. 2 medium. Ninety-seven of these OprF+ revertants were as susceptible to carbenicillin and norfloxacin as the pretherapy isolate. One of these revertants was characterized in more detail and shown to be indistinguishable in all properties from the pretherapy isolate. It is proposed that the multiple-antibiotic-resistance (Mar) phenotype of this mutant resulted from a single pleiotropic mutation.

Anti-Bacterial Agents↗
PubMed1991

Paraspinal tumors: techniques and results of brachytherapy.

Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.

Brachytherapy↗
PubMed1991

Pseudomonas aeruginosa outer membrane protein OprH: expression from the cloned gene and function in EDTA and gentamicin resistance.

Overexpression of major outer membrane protein OprH of Pseudomonas aeruginosa as a result of mutation (in strain H181) or adaptation to low Mg2+ concentrations (in parent strain H103) is accompanied by increased resistance to polymyxin B, gentamicin, and EDTA. A 2.8-kb EcoRI fragment containing the oprH gene was subcloned into several different expression plasmids in Escherichia coli. These experiments showed that significant levels of OprH could be produced from a promoter on the EcoRI fragment; that the cloned oprH gene was not regulated by Mg2+ deficiency; that there were no differences in the expression of OprH in any construction, regardless of whether the gene from strain H103 or its OprH-overexpressing, polymyxin B-resistant derivative, strain H181, was used; and that overexpression of OprH in E. coli to the level observed in P. aeruginosa H181 did not result in a resistance phenotype. These results favored the conclusion that the mutation in strain H181 was a regulatory rather than a promoter mutation. The oprH gene was cloned behind the benzoate-inducible pm promoter in plasmid pGB25 and transferred to P. aeruginosa H103. Overexpression of OprH from the cloned gene in H103/pGB25 resulted in EDTA resistance but not polymyxin B resistance. This result suggested that another factor, possibly lipopolysaccharide, was affected by the mutation in strain H181. Consistent with this suggestion was the demonstration that mutants of strain H181 with alterations in lipopolysaccharide had reverted to wild-type polymyxin B susceptibility but had unaltered gentamicin and EDTA resistance. These data were consistent with the hypothesis that OprH replaces outer membrane-stabilizing divalent cations.

Aminoglycosides↗
PubMed1991

Adjuvant brachytherapy for treatment of chest wall sarcomas.

Thirty patients treated with surgical resection and brachytherapy for chest wall sarcoma at Memorial Sloan-Kettering Cancer Center from 1980 through 1987 were reviewed. Patients selected to receive adjuvant irradiation were those for whom there was doubt as to the completeness of surgical resection. Overall 5-year survival and locoregional control after brachytherapy were 65% and 54%, respectively. Locoregional control was similar for tumors treated at initial diagnosis (12 patients), at the time of recurrence (13 patients), or for tumors that were metastatic to the chest wall (five patients). Six patients with tumors larger than 10 cm in maximum dimension had a locoregional recurrence rate of 69% versus a recurrence rate of 39% for 18 patients with smaller tumors (p = 0.27). Fifty-four percent of high-grade tumors recurred locoregionally versus 28% of low-grade tumors (p = 0.37). Bone invasion or the presence of positive resection margins was not clearly associated with a higher locoregional failure rate. Only one patient (1/28; 7%) was known to have had recurrence within the irradiated area. Eight patients (8/28; 37%) had recurrence adjacent to the implanted area, and the precise failure site could not be determined for the remaining two patients. Because of the relatively high risk of regional versus in-field recurrence, patients with chest wall sarcoma who receive adjuvant treatment should be treated primarily with external-beam irradiation to allow more generous coverage of the tumor bed. Brachytherapy could be used as a tumor bed "boost" treatment. In patients undergoing resection of recurrent tumor in a previously irradiated site, adjuvant brachytherapy, without external-beam irradiation, should be considered to reduce the risk of extensive soft tissue necrosis.

Adolescent↗
PubMed1990

Neoadjuvant chemotherapy and surgery of cancer of the esophagus.

Neoadjuvant, or pre-operative, chemotherapy for esophageal cancer has become an area of increasing interest because of the failure of conventional therapy (surgery or radiation) to improve disease-free or overall survival. Several autopsy series have demonstrated that, in many symptomatic Western patients, esophageal cancer is a systemic disease. Neoadjuvant chemotherapy thus, in theory, allows a simultaneous attack on both the primary and metastatic disease. A number of single-arm, phase II multi-modality trials have been completed. Toxicities of chemotherapy, while substantial, have been tolerable. With careful attention to detail, operative morbidity and mortality has not been increased. Large-scale randomized trials, needed to evaluate the impact of this technique on disease-free and overall survival, have been designed and will shortly be activated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.

Analysis of Variance↗
PubMed1989

New intraoperative brachytherapy techniques for positive or close surgical margins.

Tumors attached or adjacent to critical structures can often not be completely resected or resected with adequate surgical margins. Sites involving major blood vessels, the paravertebral spaces, or critical abdominal structures often present technical difficulties for standard brachytherapy procedures using I-125 or Ir-192 implants. These techniques allow for a high-dose delivery to the tumor bed with minimal normal tissue toxicity. A relatively simple and accurate method is described using I-125 seeds in Vicryl suture threaded through Gelfoam. These permanent implant procedures with radioactive I-125 seeds effectively treat small residual tumors or suspicious margins where standard brachytherapy techniques may be unsatisfactory and technically difficult to perform.

Adult↗
PubMed1988

Enrichment of CD34 (My10)-positive myeloid and erythroid progenitors from human marrow and their growth in cultures supplemented with recombinant human granulocyte-macrophage colony-stimulating factor.

Myeloid and erythroid progenitor cells were enriched from human marrow by selecting CD34-positive (CD34 + ve) cells, labeled with the My10 (HPCA-1) antibody, using a fluorescence-activated cell sorter. Seventy-one percent of CD34 + ve cells were blasts and most of these were too primitive to be identified by standard morphological criteria. On average, 9.5% of CD34 + ve cells formed clones after 14 days of culture in semisolid medium supplemented with erythropoietin and medium conditioned by 5637 bladder carcinoma cells. Over 2.5% of CD34 + ve cells were day-14 myeloid colony-forming cells and 2.4% were erythroid colony (burst)-forming progenitors. The remaining progenitors formed myeloid and erythroid clusters. A subpopulation of day-14 myeloid colony-forming cells failed to respond to recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) after accessory cells were removed during enrichment, so it appears that this factor can induce myeloid growth indirectly as well as directly. Recombinant human GM-CSF also supported erythroid colony-formation in cultures of CD34 + ve cells, which suggests that this hemopoietin may act directly on erythroid progenitors.

Antigens, CD34↗
PubMed1986

VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors.

One hundred sixty-six patients with germ-cell tumors (GCT) of the testis, retroperitoneum, and mediastinum were treated with cyclophosphamide, vinblastine, bleomycin, dactinomycin, and cisplatin (VAB-6), with and without maintenance chemotherapy. The overall complete response (CR) rate was 78%, 67% to chemotherapy alone, and 11% after chemotherapy and resection of viable residual cancer. The CR rate in all patients with seminoma was uniformly high, while the CR rate of patients with testicular nonseminomatous germ-cell tumors (79%) was superior to that of similar tumors of extragonadal origin (60%). The overall relapse rate was 12%, and was greater in tumors of extragonadal origin (21%) than in those of testicular origin (11%). Three relapses occurred after 2 years. Maintenance chemotherapy did not prolong either relapse-free or total survival. Toxicity was tolerable, and there were no treatment deaths. No Raynaud's phenomena have occurred, with a minimum duration since start of therapy of 36 months. VAB-6 is an effective chemotherapy regimen in patients with GCT with no treatment-related deaths and a majority of patients requiring only 3 months of treatment.

Adolescent↗
PubMed1986

Cisplatin, vindesine, and mitoguazone in the treatment of esophageal cancer.

Forty-two patients with epidermoid carcinoma of the esophagus were treated with the three-drug combination of cisplatin, vindesine, and mitoguazone (DVM). Twenty patients had locoregional disease and 22 had extensive disease. Of 39 patients evaluable for response, 16 (41%) had complete or partial remission (95% confidence limits, 26%-56%). Of 14 patients with locoregional disease treated prior to surgery, 12 (86%) had resectable disease. There was one death associated with surgery (7.1%). Six of these 14 patients remain alive and free of disease. The median duration of remission for patients with extensive disease was 3 months (range, 2-8). As was the case for an earlier study involving cisplatin, vindesine, and bleomycin, the dose-limiting toxic effect for DVM was leukopenia (median wbc count nadir, 1800/mm3). No clinical evidence of pulmonary toxicity was seen. DVM had moderate activity in esophageal cancer, with acceptable toxicity. Although the risks of pulmonary damage were decreased, the substitution of mitoguazone for bleomycin did not improve the major dose-limiting toxicity of myelosuppression.

Adult↗
PubMed1985

Adenocarcinoma of the esophagus and gastroesophageal junction. Prognostic factors and results of therapy.

Adenocarcinomas of the esophagus and gastroesophageal junction (AE and GE) are uncommon neoplasms with a poor prognosis. AE or GE are usually analyzed as part of the larger group of carcinomas in patients with either epidermoid carcinoma of the esophagus or with gastric cancer. The prognostic variables and outcome of therapy for patients with AE and GE alone have not been well described. The records of 131 patients treated at Memorial Hospital during the period 1978 to 1982 were reviewed. The majority underwent surgery as their primary therapy. Clinical staging was found to be highly inaccurate, with almost all patients having Stage III disease at surgery. Operative mortality was 7.1%. Adjuvant chemotherapy did not appear to influence survival. Treatment of advanced disease with either conventional or investigational agents yielded modest objective response rates. Prognostic variables for those presenting with locoregional disease who were candidates for potentially curative surgery were analyzed. Only the presence or absence of weight loss and location of the primary tumor (AE versus GE) were significant variables. A model for predicting survival was employed.

Actuarial Analysis↗
PubMed1985

Surgical treatment of spinal cord compression in patients with lung cancer.

We analyzed the clinical features, radiological findings, and results of surgical treatment in a series of 25 patients with lung cancer and invasion of the spine. In 12 of the 25 (40%) patients, involvement of the spine was present at the time of initial presentation of malignancy. Computed tomography revealed the presence of a large paravertebral soft tissue mass with destruction of adjacent ribs in the majority. The surgical approach consisted of an anterolateral exposure through a formal thoracotomy in 22 patients and a thoracoabdominal flank approach in the 3 patients with lumbar lesions. All gross tumor was resected from the involved paravertebral tissues, vertebral body, and epidural space. Immediate stabilization of the spine was then achieved with methyl methacrylate. Local brachytherapy (iridium-192 implants) was used in 19 patients. After treatment, 87% were ambulatory, and 67% maintained ambulation for more than 6 months. Our data suggest that compression of the spinal cord in many patients with lung cancer results from direct extension of tumor through the chest wall. Because the majority of such patients often have localized disease involving the spine, aggressive surgical treatment is indicated.

Adenocarcinoma↗
PubMed1984

Cisplatin and bleomycin in the treatment of esophageal carcinoma. A final report.

During the period from September, 1976 to June, 1979, 70 patients with locoregional or extensive epidermoid carcinoma of the esophagus were treated with the two-drug combination of cisplatin and bleomycin (DB). For the 43 patients with locoregional disease (LRD), DB was used prior to surgery and/or radiation therapy; it was the primary treatment for 27 patients with extensive disease (ED). The major objective response rates [complete remission (CR) and partial remission (PR)] to DB for the LRD and ED groups were 14% and 17%, respectively, for an overall response rate of 15%. For the LRD group, the minimum follow-up was 42 months; four patients (10%) remain alive and free of disease. The median survival of 34 patients treated with DB preoperatively was 10 months, which did not differ significantly from that of a historic control group receiving preoperative radiation therapy. The median duration of response for ED patients was 6 months, and the median survival for the entire ED group was 4 months. DB alone had only modest activity in epidermoid carcinoma of the esophagus.

Adult↗
PubMed1983

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Adult↗