Biomedical subjects

B A Murphy

Publications and source records attributed to B A Murphy.

At least 19 recordsLinked to original sources

PubMed2007

Changes in excitability of the cortical projections to the human tibialis anterior after paired associative stimulation.

Paired associative stimulation (PAS) based on Hebb's law of association can induce plastic changes in the intact human. The optimal interstimulus interval (ISI) between the peripheral nerve and transcranial magnetic stimulus is not known for muscles of the lower leg. The aims of this study were to investigate the effect of PAS for a variety of ISIs and to explore the efficacy of PAS when applied during dynamic activation of the target muscle. PAS was applied at 0.2 Hz for 30 min with the tibialis anterior (TA) at rest. The ISI was varied randomly in seven sessions (n = 5). Subsequently, PAS was applied (n = 14, ISI = 55 ms) with the TA relaxed or dorsi-flexing. Finally, an optimized ISI based on the subject somatosensory evoked potential (SEP) latency plus a central processing delay (6 ms) was used (n = 13). Motor-evoked potentials (MEPs) were elicited in the TA before and after the intervention, and the size of the TA MEP was extracted. ISIs of 45, 50, and 55 ms increased and 40 ms decreased TA MEP significantly (P = 0.01). PAS during dorsi-flexion increased TA MEP size by 92% (P = 0.001). PAS delivered at rest resulted in a nonsignificant increase; however, when the ISI was optimized from SEP latency recordings, all subjects showed significant increases (P = 0.002). No changes in MEP size occurred in the antagonist. Results confirm that the excitability of the corticospinal projections to the TA but not the antagonist can be increased after PAS. This is strongly dependent on the individualized ISI and on the activation state of the muscle.

Adult↗

PubMed2006

Altered cortical integration of dual somatosensory input following the cessation of a 20 min period of repetitive muscle activity.

The adult human central nervous system (CNS) retains its ability to reorganize itself in response to altered afferent input. Intracortical inhibition is thought to play an important role in central motor reorganization. However, the mechanisms responsible for altered cortical sensory maps remain more elusive. The aim of the current study was to investigate changes in the intrinsic inhibitory interactions within the somatosensory system subsequent to a period of repetitive contractions. To achieve this, the dual peripheral nerve stimulation somatosensory evoked potential (SEP) ratio technique was utilized in 14 subjects. SEPs were recorded following median and ulnar nerve stimulation at the wrist (1 ms square wave pulse, 2.47 Hz, 1x motor threshold). SEP ratios were calculated for the N9, N11, N13, P14-18, N20-P25 and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar (MU) stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median (M) and ulnar (U) nerves. There was a significant increase in the MU/M + U ratio for both cortical SEP components following the 20 min repetitive contraction task, i.e. the N20-P25 complex, and the P22-N30 SEP complex. These cortical ratio changes appear to be due to a reduced ability to suppress the dual input, as there was also a significant increase in the amplitude of the MU recordings for the same two cortical SEP peaks (N20-P25 and P22-N30) following the typing task. No changes were observed following a control intervention. The N20 (S1) changes may reflect the mechanism responsible for altering the boundaries of cortical sensory maps, changing the way the CNS perceives and processes information from adjacent body parts. The N30 changes may be related to the intracortical inhibitory changes shown previously with both single and paired pulse TMS. These findings may have implications for understanding the role of the cortex in the initiation of overuse injuries.

Adult↗

PubMed2006

Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity.

In mares, obesity is associated with continuous reproductive activity during the non-breeding season. To investigate the effect of obesity and associated alterations in metabolic parameters on the oestrous cycle, two related studies were conducted. In Experiment 1, obese (body condition score > 7) mares were fed ad libitum or were moderately feed restricted during the late summer and autumn months. Feed restriction did not alter the proportion of mares entering seasonal anoestrus. However, obese mares exhibited a significantly longer duration of the oestrous cycle, significant increases in circulating concentrations of leptin and insulin, and decreased insulin sensitivity and concentrations of thyroxine compared with feed-restricted mares throughout the experiment. Experiment 2 was designed to investigate the effects of administration of the insulin-sensitising drug metformin hydrochloride on insulin sensitivity and the characteristics of the oestrous cycle in obese mares. In a dose-response trial, metformin increased insulin sensitivity after 30 days following administration of 3 g day(-1), but not 6 or 9 g day(-1), compared with controls receiving vehicle only. However, there were no differences in insulin sensitivity or oestrous cycle characteristics between control and metformin-treated groups when the 3 g day(-1) dose was tested for a longer period of 2 months. These results demonstrate that obesity is associated with aberrations in the oestrous cycle and perturbations in several markers of metabolic status. The results also indicate that metformin is not an effective long-term monotherapy for increasing insulin sensitivity in horses at the doses tested. Additional studies are needed to examine possible effects of increasing insulin sensitivity on reproductive activity in obese mares.

Animals↗

PubMed2004

The functional assessment of cancer therapy-BRM (FACT-BRM): a new tool for the assessment of quality of life in patients treated with biologic response modifiers.

PURPOSE: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire. METHODS: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure. RESULTS: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status. CONCLUSIONS: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers.

Activities of Daily Living↗

PubMed2004

Development of a model for inducing transient insulin resistance in the mare: preliminary implications regarding the estrous cycle.

Peripheral insulin resistance is the failure of proper cellular glucose uptake in response to insulin. Insulin resistance and hyperinsulinemia are associated with several disease states in the horse and reproductive function disturbances in humans, including polycystic ovarian syndrome. To test the hypothesis that insulin resistance (IR) and hyperinsulinemia disrupt the estrous cycle in mares, two experiments were conducted to first develop a model to induce IR and to then examine the effect of this model on the duration of the estrous cycle. In Exp. 1, a hyperinsulinemic-euglycemic clamp (HEC) procedure was performed on seven mares to determine insulin sensitivity before and immediately following infusion of a heparinized lipid solution. The HEC procedure was repeated 1 wk after lipid infusion. Mares developed IR following the lipid infusion (P < 0.05), and some individuals maintained IR for up to 1 wk. Mares also exhibited increased blood insulin both immediately following treatment and 1 wk later (P < 0.05). In Exp. 2, induction of insulin resistance by lipid solution was not accompanied by changes in circulating concentrations of luteinizing hormone, and duration of the luteal phase, compared with the duration of untreated luteal phases. Nonetheless, lipid infusion and the resultant insulin resistance were associated with an increased interovulatory period (P < 0.05), and peak concentrations of progesterone (P < 0.05) were higher during the treated vs. untreated luteal phases of the estrous cycle. The results from the preliminary study suggest that infusion of a lipid solution may induce transient insulin resistance and hyperinsulinemia. The resulting insulin resistance and hyperinsulinemia may modify characteristics of the estrous cycle, perhaps at the level of the ovary.

Animals↗

PubMed2003

Rapid reversible changes to multiple levels of the human somatosensory system following the cessation of repetitive contractions: a somatosensory evoked potential study.

OBJECTIVE: Numerous somatosensory evoked potential (SEP) studies have provided clear evidence that during repetitive voluntary movement, the transmission of somatosensory afferent information is attenuated. The objective of this work was to determine if this gating phenomenon could persist beyond the period of repetitive movement. METHODS: We recorded spinal, brainstem, and cortical SEPs to median nerve stimulation before and immediately after a modified 20 min repetitive typing task that did not involve the thenar muscles. RESULTS: There were significant decreases in pre-central cortical and subcortical SEP amplitudes for several minutes following task cessation. CONCLUSIONS: These results demonstrate the persistence of the gating phenomenon beyond the cessation of the actual repetitive movement. They also indicate that plastic changes do occur in cortical and subcortical components of the somatosensory system, following voluntary repetitive contractions. SIGNIFICANCE: The persistence of changes in somatosensory processing beyond the period of repetitive activity may be relevant to the initiation of overuse injuries.

Adult↗

PubMed2003

Changes in median nerve somatosensory transmission and motor output following transient deafferentation of the radial nerve in humans.

OBJECTIVE: To determine if transient anaesthetic deafferentation of the radial nerve would lead to alterations in processing of early somatosensory evoked potentials (SEPs) from the median nerve or alter cortico-motor output to the median nerve innervated abductor pollicis brevis (APB) muscle. METHODS: Spinal, brainstem, and cortical SEPs to median nerve stimulation were recorded before, during and after ipsilateral radial nerve block with local anaesthesia. Motor evoked potentials (MEPs) and motor cortex output maps were recorded from the APB muscle. RESULTS: There were no significant changes to most early SEP peaks. The N30 peak, however, showed a significant increase in amplitude, which remained elevated throughout the anaesthetic period, returning to baseline once the anaesthetic had completely worn off. MEP amplitude of the median nerve innervated APB muscle was significantly decreased during the radial nerve blockade. There was also a significant alteration in the APB optimal site location, and a small but significant decrease in the silent period during the radial nerve blockade. CONCLUSIONS: Transient anaesthetic deafferentation of the radial nerve at the elbow leads to a rapid modulation of cortical processing of median nerve input and output. These changes suggest an overall decrease in motor cortex output to a median nerve innervated muscle not affected by the radial nerve block, occurring concomitantly with an increased amplitude of the median nerve generated N30 SEP peak, thought to represent processing in the supplementary motor area (SMA). Independent subcortical connections to the SMA are thought to contribute to the N30 response observed in this study. Unmasking of pre-existing but latent cortico-cortical and/or thalamo-cortical connections may be the mechanism underlying the cortical SEP increases observed following radial nerve deafferentation. SIGNIFICANCE: Transient deafferentation of the radial nerve, which supplies wrist and hand extensor muscles, has been shown to alter sensory processing from and motor output to the median nerve innervated thenar muscles.

Adult↗

PubMed2001

Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.

PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.

Adult↗

PubMed2001

The GA motif: an RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs.

Two different transcription termination control mechanisms, the T box and S box systems, are used to regulate transcription of many bacterial aminoacyl-tRNA synthetase, amino acid biosynthesis, and amino acid transport genes. Both of these regulatory mechanisms involve an untranslated mRNA leader region capable of adopting alternate structural conformations that result in transcription termination or transcription elongation into the downstream region. Comparative analyses revealed a small RNA secondary structural element, designated the GA motif, that is highly conserved in both T box and S box leader sequences. The motif consists of two short helices separated by an asymmetric internal loop, with highly conserved GA dinucleotide sequences on either side of the internal loop. Site-directed mutagenesis of this motif in model T and S box leader sequences indicated that it is essential for transcriptional regulation in both systems. This motif is similar to the binding site of yeast ribosomal protein L30, the Snu13p binding sites found in U4 snRNA and box C/D snoRNAs, and two elements in 23S rRNA.

Bacteria↗

PubMed2001

Cytology of endolymphatic sac tumor.

A 77-year-old man presented with decreased mental status and an enhancing partially cystic tumor along the left tentorium on magnetic resonance imaging after mastoidectomy and petrosectomy for an "auditory canal tumor." Smears of the aspirated cyst fluid revealed rare epithelial cell clusters, some with papillary features, foamy macrophages, and blood. The cells were orderly, with fairly bland nuclei and well-defined cell borders. The cell block contained similar epithelium, with cells containing eosinophilic and focally vacuolated cytoplasm, some with pigmented granules resembling hemosiderin. Numerous foam cells were also present. Review of the patient's previous and concurrent resection material showed an endolymphatic sac tumor, a rare neoplasm that arises in the endolymphatic sac in the temporal bone. The previously undescribed cytologic features of this rare neoplasm are discussed.

Aged↗

PubMed2001

Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma.

Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.

Adult↗

PubMed2001

Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393).

Recurrent or metastatic squamous carcinoma of the head and neck (RMSCHN) is a modestly chemoresponsive tumor; however, currently available agents have failed to improve survival. New active agents are needed for the treatment of this disease. Topotecan is a topoisomerase inhibitor that demonstrated initial promising activity in squamous carcinoma of the head and neck. The Eastern Cooperative Oncology Group conducted a phase II trial of topotecan to determine the efficacy and toxicity of a weekly treatment schedule in patients with RMSCHN. Patients with metastatic or locally recurrent squamous carcinoma of the head and neck were treated with topotecan 1.5 mg/m2 x 24 hours by continuous infusion on days 1, 8, 15, and 22 of each 35-day cycle. Patients were stratified in two cohorts: chemonaive and previously treated. Sixteen chemonaive and 16 previously treated patients were registered on study. Grade III/IV neutropenia and anemia occurred in 16% and 18% of patients, respectively. No responses were observed in either cohort. Median survival for previously untreated patients was 4.6 months and 3.2 months for previously treated patients. Topotecan failed to demonstrate efficacy in patients with RMSCHN. Further evaluation of this agent is not planned.

Adult↗

PubMed2001

Topoisomerase I inhibitors in the treatment of head and neck cancer.

Traditionally, the role of chemotherapy in the treatment of squamous carcinoma of the head and neck has been confined to patients with recurrent or metastatic disease who are deemed incurable with surgery or radiation therapy. Over the past decade, however, the role of chemotherapy has changed dramatically. The use of primary combined chemoradiation to preserve function or to enhance survival in patients with unresectable disease has become a standard approach. As the use of chemotherapy in squamous carcinoma of the head and neck has expanded, investigators have been interested in identifying new active agents. Topoisomerase I inhibitors, a new class of drugs, have been found to be active in a number of solid and hematologic malignancies. Three topoisomerase I inhibitors have been investigated in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: 9-aminocamptothecin (9-AC), topotecan (Hycamtin), and irinotecan (CPT-11, Camptosar). Neither 9-AC nor topotecan has demonstrated clinically significant activity in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. In contrast, irinotecan has demonstrated a modest overall response rate of 21.2% (95% confidence interval [CI] = 9%-38.9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted.

Antineoplastic Agents↗

PubMed2000

Delirium.

Delirium is a true medical emergency that can masquerade as chronic dementia or functional psychosis and obscure the causative underlying physical or toxic disorder. In most cases, a well-focused history and thorough physical examination can unmask the delirium and reveal the medical or toxic problem. Carefully selected diagnostic testing can be required. Emergency management of the medical or toxic disorder is the same as in nondelirious patients. Control of agitated or aggressive behavior with pharmacologic or physical restraints and special support measures are required to facilitate ED care. Delirious patients whose symptoms do not totally resolve in the ED must be admitted.

Delirium↗

PubMed2000

Use of a mental rotation reaction-time paradigm to measure the effects of upper cervical adjustments on cortical processing: a pilot study.

OBJECTIVES: To investigate the potential usefulness of a mental rotation paradigm in providing an objective measure of spinal manipulative therapy. To determine if cortical processing, as indicated by response time to a mental rotation reaction-time task, is altered by an upper cervical toggle recoil adjustment. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Chiropractic college clinical training facility. PARTICIPANTS: Thirty-six chiropractic student volunteers with clinical evidence of upper cervical joint dysfunction. INTERVENTION: Participants in the experimental group received a high-velocity, low-amplitude upper cervical adjustment. A non-intervention group was used to control for improvement in the mental rotation task as a result of practice effects. OUTCOME MEASURES: Reaction time was measured for randomly varying angular orientations of an object appearing either as normal or mirror-reversed on a computer screen. RESULTS: The average decrease in mental rotation reaction time for the experimental group was 98 ms, a 14.9% improvement, whereas the average decrease in mental rotation reaction time for the control group was 58 ms, an 8. 0 improvement. The difference scores after the intervention time were significantly greater for the experimental group compared with the control group, as indicated by a one-tailed, 2-sample, equal variance Student t test, (P < 05). CONCLUSION: The results of this study have demonstrated a significant improvement in a complex reaction-time task after an upper cervical adjustment. These results provide evidence that upper cervical adjustment may affect cortical processing.

Adult↗

PubMed2000

Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.

PURPOSE: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed. RESULTS: Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy. CONCLUSION: Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.

Administration, Oral↗

PubMed2000

Activator protein-1 mediates induced but not basal epidermal growth factor receptor gene expression.

BACKGROUND: The epidermal growth factor receptor (EGFR) is expressed at different levels in many cell types and found overexpressed in many cancers. EGFR expression is increased or decreased in response to extracellular stimuli. We examined the effect of increased c-Jun expression on EGFR promoter activity. MATERIALS AND METHODS: We used DNAse I foot-printing analysis to determine the binding of activator protein 1 (AP-1) to the promoter region. We also used cotransfection experiments and western blotting analysis to determine the effect of AP-1 family members on EGFR expression. RESULTS: AP-1 was able to bind to at least seven sites in the EGFR promoter region. Cotransfection of MCF-7 cells with a c-Jun expression vector and the EGFR promoter reporter resulted in a 7-fold increase in promoter activity. JunB, but not c-fos, also enhanced the EGFR promoter activity. An A-Fos-dominant negative shown to inhibit Jun-dependent transactivation was able to prevent c-Jun induction of the promoter activity, but only slightly decreased the basal activity of the promoter. Furthermore, the A-Fos dominant negative was able to inhibit phorbol ester induction of the EGFR promoter. Examination of EGFR expression of MCF-7 stable cell lines that overexpress c-Jun revealed an increase in EGFR expression. Additionally, a cisplatin-resistant cell line, A2780/CP70, which has an increase in AP-1 activity compared with the parental cell line, A2780, was found to have an increase in EGFR level. CONCLUSIONS: These results indicate that AP-1 can act to increase the expression of EGFR and may play a role in upregulation of EGFR in cancer cells.

3T3 Cells↗

PubMed1999

Combined-modality therapy for locoregionally advanced head and neck cancer.

Traditionally, treatment for locally advanced resectable head and neck cancer has been surgical resection followed by postoperative radiation. In unresectable patients, primary radiation has been the mainstay of treatment. In an attempt to improve local control and survival, chemotherapy has been investigated as an adjunct to locoregional treatment. Induction or adjuvant chemotherapy in combination with primary surgical resection has failed to demonstrate an improvement in either local control or survival. Induction chemotherapy followed by radiation therapy is an acceptable alternative to surgical resection for organ preservation. A randomized trial in patients with advanced oropharyngeal carcinoma and another in advanced nasopharyngeal carcinoma have shown an improvement in survival with the use of concomitant chemotherapy and radiation compared to radiation alone. Other prospective randomized trials as well as three meta-analyses also demonstrate improved survival with the addition of concomitant chemotherapy for locally advanced disease. Newer chemotherapeutic agents are currently under investigation, particularly those with radiosensitizing properties. Chemotherapy as part of primary therapy, however, should be used judiciously, and should be based on an assessment of the potential risks and benefits to each patient.

Antineoplastic Combined Chemotherapy Protocols↗