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Biomedical subjects

J R Clark

Publications and source records attributed to J R Clark.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Circulating immune complexes and chemotherapy response in patients with head and neck cancer.

An assay which could prospectively predict a response to chemotherapy prior to instituting therapy would be beneficial, especially for nonresponders. We evaluated at random a total of 50 patients with previously untreated stage III and IV head and neck squamous cell carcinoma for T-cell subsets and levels of circulating immune complexes (CIC). Of this group 23 patients had induction chemotherapy as their first modality of treatment. These patients received standard protocols of therapy consisting of cisplatin, 5-fluorouracil, methotrexate, and bleomycin. Of the laboratory measures assessed, only CIC correlated with clinical response to chemotherapy [no response (NR), partial response (PR), complete response (CR)] at the completion of the induction period (two to four cycles). Levels of CIC were determined by a polyethylene glycol (PEG) precipitation assay, and measured by spectrophotometry at 280 nm. In our population of all head and neck cancer patients, CIC were elevated (mean +/- SD values: 0.475 +/- 3.8 compared with controls: 0.184 +/- 0.07). In the NR group, the mean +/- SD was 0.707 +/- 0.43 (P = 0.001). Complete responders had a mean value of 0.332 +/- 0.21; partial responders had a mean value of 0.255 +/- 0.13. On the basis of the values determined, patients with markedly elevated levels of CIC would be predicted to respond poorly, or not all, to current induction chemotherapy protocols.

Antigen-Antibody Complex↗
PubMedDate not supplied

Primary site management following induction chemotherapy with cis-platinum, 5-fluorouracil, and leucovorin.

A phase II clinical trial was initiated in 1987 to evaluate a new induction regimen of cis-platinum, 5-fluorouracil, and leucovorin (PFL) for patients with stages III-IV squamous cell carcinoma of the head and neck. Ninety patients were treated and followed for a median duration of 18 months. The median age was 55 and 87% of the patients had stage IV disease. The rates of complete and overall clinical response following three cycles of PFL were 57% and 80%, respectively; the rate of complete response at the primary site was 72%. Eighty-four percent of patients were treated to the primary site with radiation alone (median dose 68 Gy in daily 1.8-Gy fractions) irrespective of the location of the primary site or initial T-stage. The acute tolerance to full-course radiation following PFL was acceptable. The actuarial rate of primary site control for patients treated with radiation was 67% at 36 months. An important prognostic indicator for primary site control was a complete clinical response to induction PFL. For patients who achieved a complete response, radiation or surgery followed by radiation controlled primary site disease equally well at 70%. Patients with a partial response did less well. For these patients, surgery and radiation appeared slightly better than radiation alone.

Actuarial Analysis↗
PubMedDate not supplied

Evolving role of surgery after induction chemotherapy and primary site radiation in head and neck cancer.

Chemotherapy, as preliminary treatment before surgery and/or radiation for advanced squamous cell carcinoma of the head and neck, is no longer novel. In prospective trials to date, however, multiple agent induction chemotherapy has yet to demonstrate the initial presumptive promise of improved rates of cure. As an alternate goal, there has emerged a renewed attentiveness toward limiting treatment morbidity, several strategies for which may be considered. Extirpative, often radical, surgery on the primary site of disease usually represents the most significant threat to life quality. Various ways of limiting surgical morbidity will be considered by way of introduction. The trends of head and neck cancer treatment over the decades, leading into the era of induction chemotherapy and refined radiation techniques, will be described. At the combined Dana-Farber/New England Deaconess Head and Neck Oncology Clinic, an experience with over 300 patients receiving induction chemotherapy for advanced head and neck cancer has been analyzed with an emphasis on the postulate of lessening the extent of surgery in appropriately selected patients. In a comparison between trials initiated in 1980 and 1987, improved complete response rates from 26 to 57% were documented. Survival rates were identical, but the use of planned primary site ablative surgery was decreased from 47 to 14%. While some increase in local failure has been noted in patients treated by primary site radiation alone, surgical salvage appeared to be more effective. The implication of these trends for patterns of failure and surgical salvage and data concerning the need for neck dissection in this group of patients will be briefly summarized. Other trials addressing organ-preservation strategies will also be referenced and the dichotomy between survival-based studies and morbidity-limiting studies illustrated. Independent trends in radiation technique as a potential substitute for traditional surgical practice will be reviewed.

Antineoplastic Agents↗
PubMedDate not supplied

Nasopharyngeal carcinoma: the Dana-Farber Cancer Institute experience with 24 patients treated with induction chemotherapy and radiotherapy.

Nasopharyngeal carcinoma traditionally has been treated with radiotherapy alone. Although the probability of cure for patients with stage I and II nasopharyngeal carcinoma is high, the probability of cure for patients with stage III and IV disease is poor because of a higher rate of local-regional and distant failure. Between February 1981 and August 1986, 24 patients with previously untreated, stage IV nasopharyngeal carcinoma were treated with two to four monthly courses of cisplatin-based combination chemotherapy prior to radiotherapy. A response to induction chemotherapy was recorded in 75% of patients (29% complete response and 46% partial) prior to radiotherapy. By actuarial estimate with a median follow-up of 42 months, the 2-year failure-free survival for all patients was 57%. In conclusion, induction chemotherapy has significant activity in nasopharyngeal carcinoma. The toxicity of this approach, as well as the influence of initial histopathology and response to chemotherapy on survival, will be discussed.

Adolescent↗
PubMedDate not supplied

Assessment of risk reduction strategies for the management of agricultural nonpoint source pesticide runoff in estuarine ecosystems.

Agricultural nonpoint source (NPS) runoff may result in significant discharges of pesticides, suspended sediments, and fertilizers into estuarine habitats adjacent to agricultural areas or downstream from agricultural watersheds. Exposure of estuarine fin fish and shellfish to toxic levels of pesticides may occur, resulting in significant declines in field populations. Integrated pest management (IPM), best management practices (BMP), and retention ponds (RP) are risk management tools that have been proposed to reduce the contaminant risk from agricultural NPS runoff into estuarine ecosystems. Field studies were conducted at three sites within coastal estuarine ecosystems of South Carolina (SC) from 1985 to 1990 that varied in terms of the amount and degree of risk reduction strategies employed. An intensively managed (IPM, BMP, and RP) agricultural treatment site (TRT) was studied for pesticide runoff impacts. From 1985 to 1987, there were minimal (some IPM and BMP) management activities at TRT, but from 1988 to 1990, TRT was managed using an intensive risk reduction strategy. A second unmanaged agricultural growing area, Kiawah (KWA), was also studied and compared with TRT in terms of pesticide runoff and the resulting impacts on grass shrimp (Palaemonetes pugio) and mummichogs (Fundulus heteroclitus). A third, non-agricultural, reference site (CTL) was used for comparing results from the managed and unmanaged agricultural sites. In situ toxicity tests and field samples of the grass shrimp populations were conducted at each site and compared in terms of survival and the effectiveness of current risk reduction strategies. Significant runoff of insecticides (azinphosmethyl, endosulfan, and fenvalerate) along with several fish kills were observed at TRT prior to the implementation of rigorous risk reduction methods. A significant reduction of in stream pesticide concentrations (up to 90%) was observed at TRT following the implementation of strict NPS runoff controls, which greatly reduced impacts on estuarine fish and shellfish. At the unmanaged KWA, continued impacts due to the runoff of these insecticides were observed, along with several fish kills. Additional monitoring indicated that gravid female grass shrimp populations from KWA had elevated levels of P-glycoprotein (P-gp), a multidrug resistance protein, which may transport various pesticides across cellular membranes. Comparison of field results with laboratory toxicity tests established that pesticide exposure was the primary cause of observed field impacts at each site. These findings clearly indicate the value of an integrated risk reduction strategy (BMP, IPM, and RP) for minimizing impacts from NPS agricultural pesticide runoff.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

A prospective study of hprt mutant and mutation frequencies in treated cancer patients.

We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗