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At least 469 records · Page 26Linked to original sources

First results of a randomized clinical trial of fast neutrons compared with X or gamma rays in treatment of advanced tumours of the head and neck. Report to the Medical Research Council.

Results of the first randomized clinical trial to compare the effects of fast neutrons and those of x or gamma rays (photons) in treating patients with advanced tumours of the head and neck are reported. In 37 out of 52 patients treated with neutrons and 16 out of 50 treated with photons the local tumour completely regressed; the tumour later recurred in nine of the 16 photon patients but in none of the 37 neutron patients. The advantages to the neutron-treated patients were seen in tumours of well and poorly differentiated histology and in each site. Complications after treatment did not differ significantly between the groups. Despite these substantial differences in local control of the tumour there were no significant differences in mortality between the series. A detailed study of the effective doses and the response of tumours and normal tissue in each series indicated that the improved results from neutron therapy were due to differences in the biological quality of the beam and not to the rather higher average effective dose in the neutron series. To assess the long-term effects of neutron treatment patients in earlier stages of disease and with smaller tumours should be included in the next phase of the trial.

Clinical Trials as Topic↗

Parathyroid hormone related protein in oral squamous cell carcinomas invading the mandible.

AIM: To assess parathyroid hormone related protein (PTHrP) as a candidate biochemical marker of invasion of the mandible by oral squamous cell carcinoma. METHODS: Tumour PTHrP concentrations were quantitated by immunoassay, and PTHrP was detected by immunohistochemistry, in a cohort of 24 primary squamous cell carcinomas of the mandible. RESULTS: PTHrP was identified in all tumours examined, but no correlation was found between scores of the intensity and/or consistency of staining or tumour PTHrP concentrations and the histological classification of tumour invasion. CONCLUSION: Although PTHrP was present in all squamous tumours studied, there was no correlation between PTHrP expression and pattern of tumour invasion. However, tumour derived PTHrP may act locally to influence tumour growth and differentiation and resorption of bone.

Biomarkers, Tumor↗

The adjuvant effect of lucanthone (miracil D) in clinical radiation therapy.

Clinical trials were undertaken to determine whether lucanthone (miracil D) affects radiation-induced regression in measurable pulmonary metastases and advanced squamous-cell oral and pharyngeal tumors. The time required for 50% tumor regression was decreased by approximately 50% in those patients who received lucanthone in addition to irradiation. These results indicate that lucanthone has a definite adjuvant effect when used together with irradiation.

Carcinoma, Squamous Cell↗

Clinical course of patients with squamous cell carcinoma of the upper respiratory and digestive tracts with no evidence of disease 5 years after initial treatment.

Eleven hundred sixty-three patients with squamous cell carcinoma of the upper respiratory and digestive tracts, treated from January 1948 through December 1965, had no evidence of disease five years after the initial treatment and no other manifestation of squamous cell carcinoma within the first five years. After five years, the incidence of disease at the initial location, in the vicinity, or in remote sites was found to be identical in the surgical and irradiation groups. There is a correlation between severe late complications in the irradiated patients and the volume of tissue irradiated.

Carcinoma, Squamous Cell↗

Radiotherapy for verrucous carcinoma.

Radiotherapy of verrucous carcinoma has frequently been associated with anaplastic transformation and poor response. No anaplastic transformation was observed in the 6 patients receiving radiotherapy as the primary treatment, and control of disease was favorable compared with 5 surgically treated patients. Four of the 6 undergoing radiotherapy are alive NED 1-4 years later. Review of the literature and of the University of California cases fails to substantiate an increase in anaplastic transformation in in verrucous carcinoma patients. We recommend that verrucous carcinoma be treated as other squamous cell carcinomas of similar sites and stages.

Carcinoma, Papillary↗

Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review.

Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.

Carcinoma, Squamous Cell↗

Glutathione S-transferase polymorphisms and the synergy of alcohol and tobacco in oral, pharyngeal, and laryngeal carcinoma.

Investigations of the ability of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes to alter susceptibility to head and neck squamous cell carcinoma (HNSCC) have examined gene-environment interaction in their detoxification of tobacco-associated carcinogens. Little work has been done to ask if these variant genes also modify the interaction of tobacco and alcohol in the development of HNSCC. To test this hypothesis, we conducted a case-control study, enrolling 692 incident cases of HNSCC and 753 population controls. Information about lifetime tobacco and alcohol use was ascertained through questionnaires, and genotypes for GSTM1, GSTT1, and GSTP1 were determined from constitutional DNA. Genotype frequencies were compared among cases and controls, and the association between genotypes and tobacco use was evaluated on cancer risk through logistic regression. Deletion of GSTM1 was associated with an increased risk for HNSCC [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 1.0-1.6]. GSTT1 deletion was associated with a slight decreased HNSCC risk (OR, 0.8; 95% CI, 0.6-1.0). Among those with GSTM1 present, the OR of cancer for heavy smoking was 2.6 (95% CI, 1.6-4.3) compared with 4.2 for those with the GSTM1 deleted (95% CI, 2.6-6.7). The combination of consuming 10 to 20 alcohol drinks weekly and smoking >45 pack-years was associated with a 13-fold elevated risk (OR, 12.6; 95% CI, 4.0-40.2) among the GSTM1 deleted subjects compared with an OR of 3.6 (95% CI, 1.5-8.7) among the GSTM1 present individuals. These data (showing that the GSTM1 deletion affects on the tobacco and alcohol synergy) suggest that the interaction of these carcinogens is, at least in part, driven by alcohol, enhancing the carcinogenic action of tobacco smoke.

Alcohol Drinking↗

Aberrant methylation of DPYD promoter, DPYD expression, and cellular sensitivity to 5-fluorouracil in cancer cells.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD), the initial rate-limiting enzyme in the degradation of 5-fluorouracil (5-FU), is known to be a principal factor in clinical responses to the anticancer agent 5-FU, and various reports have clearly demonstrated that DPD activity is closely correlated to mRNA levels. However, the regulatory mechanisms of DPD gene (DPYD) expression remain unclear. In this study, the regulatory mechanisms have been intensively studied. EXPERIMENTAL DESIGN AND RESULTS: A subcloned 3.0-kb fragment of the 5' region of DPYD contains a total of 60 CpG sites, suggesting that methylation status may affect the repression of DPYD. The clone showed various promoter activities that were largely correlated with mRNA levels in most cell lines, except HSC3 and HepG2. Bisulfite sequencing analysis revealed that various CpG sites around the transcription start site were abnormally methylated in cells with low DPYD expression: Reversal of hypermethylation by 5-azacytidine treatment significantly increased DPYD expression in HSC3 and HepG2 cells that showed strong promoter activity. In HepG2, in vitro methylation of the DPYD promoter directly decreased promoter activity, and 5-azacytidine treatment restored higher DPYD expression in a dose- and time-dependent manner, along with decreased sensitivity to 5-FU. CONCLUSIONS: We found that DPD activity was controlled, at least in part, at the transcription level of DPYD and that aberrant methylation of the DPYD promoter region acted as one of the repressors of DPYD expression and affected sensitivity to 5-FU in cancer cells. Our new results could lead to a more precise understanding of the molecular basis of 5-FU response.

Adenocarcinoma↗

The impact of comorbidity on outcomes.

Patients often have other diseases, illnesses, or conditions in addition to the disease under study. These other medical conditions are referred to as comorbidity. Comorbidity can impact on diagnosis, prognosis, and selection of therapy. There are a variety of instruments available to measure the type and severity of comorbid ailments. Comorbidity information can be obtained from direct discussions with the patient, a review of the medical record, or from electronic databases that contain billing information. The method of comorbidity assessment can impact on the interpretation of results. Accurate comorbid information will improve the conduct of and generalizability of clinical trials, evaluation of outcomes from observational research, population-based epidemiological studies, and patient-physician communication.

Comorbidity↗

Guanylate cyclase activity in normal and neoplastic squamous epithelia from the upper aero-digestive tract.

Cyclic nucleotides (cAMP, cGMP) are suggested to participate in the regulation of cell growth and differentiation. Guanylate cyclase is the enzyme which catalyzes the synthesis of cGMP. The basal guanylate cyclase activity was slightly higher in well-differentiated squamous cell carcinomas than in normal mucosa, but was two-fold higher in papillomas. Poorly differentiated squamous cell carcinoma did not show any increased basal activity. Stimulation with nitroprusside (NP) resulted in a 20% increased activity for normal mucosa and a 30% increase for poorly differentiated carcinomas, whereas enzyme prepared from well-differentiated squamous carcinomas and papillomas showed a two-fold increase.

Carcinoma, Squamous Cell↗

Nutrition and the oral health of the elderly.

The dental problems of the elderly, though they may seem slight, can have far-reaching effects on both health and quality of life. The complexity and variety of potential physical and psychosocial problems of older citizens require a multidisciplinary management approach. Dental team members need to target appropriate resources outside of the dental office, and nondental care providers need to attend to dental needs as well as other more evident problems. Only in this way can we help to optimize the health and longevity of this ever-increasing segment of the population.

Aged↗