alpha-chymotrypsin and Head-and-Neck-Neoplasms

Based on in vitro and on clinical evidence of protection against acute side effects of radiation, a prospective randomized, open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy.. Patients with stage T3/T4 head and neck cancer were eligible. One hundred patients from two centres were entered into the study. 60Co gamma-radiation was delivered at a standard daily radiation dose of 2 Gy in 25-35 fractions over a period of 6-7 weeks. Two lateral parallel opposing fields were used with a portal area of 10 x 15 cm. Patients assigned to the test group arm additionally received enzyme tablets orally t.i.d. starting 3 days prior to radiation therapy, and continuing up to 5 days after completion of the course of radiation therapy. Patients in the control arm were not given any drug or placebo. Acute radiation side effects were described as mucositis, skin reaction, dysphagia, and were graded at each visit during and after radiation therapy, following RTOG/EORTC criteria.. The severity (maximum extent) of acute radiation therapy side effects was significantly less in enzyme-treated patients than in control patients: mucositis (mean: 1.3 vs 2.2, P < 0.001), skin reaction (1.2 vs 2.4, P < 0.001) and dysphagia (1.4 vs 2.2, P < 0.001). The duration of these side effects as well as the sum scores of side effects were also less in the study arm.. Combination of enzyme therapy with conventional fractionated radiation therapy was feasible and well-tolerated. There was significant protection against acute side effects of radiation therapy in the study arm. Not only was the severity of acute side effects less but the duration was shorter and the time to onset was also delayed. Prospective randomized double-blind studies would verify this role of an oral enzyme therapy as standard co-medication with radiation therapy to the head and neck region.

Topics: Acute Disease; Carcinoma, Squamous Cell; Chymotrypsin; Deglutition Disorders; Drug Combinations; Endopeptidases; Head and Neck Neoplasms; Humans; Male; Middle Aged; Papain; Prospective Studies; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Skin; Stomatitis; Trypsin

The oral bacteria involved in the development of periodontitis alter the tissue conditions and modify immune responses in a way that may also influence tumor development. We investigated the prevalence of R gingipain (Rgp), a key virulence factor of the oral pathobiont Porphyromonas gingivalis, and the tissue-destructive enzymes matrix metalloproteinase 8 (MMP-8) and 9 (MMP-9) in 202 unselected consecutive oropharyngeal squamous cell carcinoma (OPSCC) samples. We further investigated the relationships between these factors and human papillomavirus (HPV) status, Treponema denticola chymotrypsin-like proteinase (Td-CTLP) immunoexpression, clinical parameters, and patient outcome.. Clinicopathological data were derived from university hospital records. Rgp, MMP-8, and MMP-9 immunoexpression was evaluated by immunohistochemistry; the immunohistochemistry of Td-CTLP and HPV has been described earlier for this patient series. Cox regression analysis including death by causes other than OPSCC as a competing risk served to assess sub distribution hazard ratios.. In multivariable survival analysis, positive tumoral MMP-9 immunoexpression predicted poor prognosis among all patients [sub distribution hazard ratio (SHR)=2.4; confidence interval (CI)=1.2-4.4, p=0.008], and especially among those with HPV-negative OPSCC (SHR=3.5; CI=1.7-7.3, p=0.001). Positive immunoexpression of Rgp in inflammatory cells was associated with favorable outcome among all patients (SHR=0.5, CI=0.2-0.9, p=0.021) and among those with HPV-negative disease (SHR=0.4, CI=0.2-0.9, p=0.022).. Our results suggest that tumoral MMP-9 may be related to poor outcome in OPSCC, especially in HPV-negative disease, while Rgp immunoexpression in inflammatory cells is associated here with better disease-specific survival (DSS).

Topics: Chymotrypsin; Gingipain Cysteine Endopeptidases; Head and Neck Neoplasms; Humans; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Porphyromonas gingivalis; Prognosis; Squamous Cell Carcinoma of Head and Neck; Virulence Factors

One method of treatment used in cancer therapy is radiotherapy which can injure the oral, pharynx or larynx mucosa and predisposes tissue to the development of fungal infections. The aim of the study paper was the mycological examinations of swabs from the oral cavity and pharynx of patients obtained prior to, in week 3, on the last day of and 3 weeks after radiotherapy, as well as isolation of fungi and identification of the selected parameter of strains pathogenecity, i.e. hydrolytic enzyme release. Forty-three patients with oral cavity, pharynx or larynx carcinoma were examined at four points during a course of radiotherapy: before treatment, in week 3 of treatment, on the last day of treatment and 3 weeks afterwards. The mycological examination was conducted based on a procedure introduced in the Department of Biology and Medical Parasitology, Medical University of Lodz. The activity of the hydrolytic enzymes was evaluated with a bioMerieux API ZYM test kit. More than 2/3 of the patients (68.2%) were found to have a fungal infection in the first examination, 4/5 (80%) in the second, about 3/5 (57.1%) in the third and all (100%) in the last examination. The release of enzymes varied, and on different stages show different inactive enzymes: at the start, alpha-chymotrypsin and alpha-mannosidase; at 3 weeks, beta-glucuronidase and alpha-mannosidase; at the end, alpha-chymotrypsin; at 3 weeks after the end, trypsin, alpha-chymotrypsin, alpha-galaktosidase and alpha-fucosidase. The most frequent species isolated from the patients treated by radiotherapy is Candida albicans and C. glabrata. The latter is characterized by resistance to the majority of antimycotic medications. The isolated strains are characterized by the highest activity of leucine arylamidase, acid phosphatase and naphthol--AS-BI-phosphohydrolase. Considering the enzymes produced, most of the strains can be included to biotypes D3, C6 and A.

Topics: Aged; Aged, 80 and over; alpha-Galactosidase; alpha-L-Fucosidase; alpha-Mannosidase; Causality; Chymotrypsin; Comorbidity; Female; Fungi; Glucuronidase; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mouth; Mycological Typing Techniques; Mycoses; Pharynx; Prevalence; Radiotherapy

Topics: Chymotrypsin; Edema; Facial Neoplasms; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Lymph Node Excision; Neoplasms; Postoperative Complications; Radiosurgery