alpha-chymotrypsin and Uterine-Cervical-Neoplasms

The use of additional therapy with an oral enzyme preparation containing trypsin, chymotrypsin and papain has been suggested for the reduction of toxicity due to radiation therapy. This study was conducted to test the efficacy and tolerability of this enzyme combination in preventing or reducing the acute side effects of radiation therapy in patients with locally advanced cervical cancer.. A prospective, randomised, open, clinical trial was carried out on 120 patients (aged 24-85 years) with locally advanced, biopsy-proven carcinomas of the uterine cervix (stages IIa, lIb or IIIb). Patients received 50 Gy of external radiation therapy over a period of 5 weeks, followed by intracavitary brachytherapy (20-30 Gy). Patients assigned to the test group (60 patients) received additional treatment with enzymes. Patients were evaluated at weekly intervals for acute radiation therapy-related side effects, according to the RTOG/EORTC grading criteria, and then after the end of radiation therapy for another 8 weeks. Occurrence of adverse events, if any, was also recorded.. The study revealed that the maximum extent of acute radiation side effects was reduced in the enzyme group: skin reactions (mean: 0.97 vs 1.68 in the control group, P < 0.001), vaginal mucosal reactions (0.55 vs 0.85, P = 0.10), genitourinary symptoms (0.93 vs 1.38, P < 0.001) and gastrointestinal reactions (1.12 vs 1.30, P = 0.12). The sum-scores during treatment, expressed as area under the curve, were significantly less in the enzyme treated patients. In the follow-up visits all observed side effects of radiation therapy were of lower intensity in the enzyme group than in the control group.. In patients with locally advanced cancer of the uterine cervix, oral enzyme therapy was found to be effective in significantly reducing radiation therapy-related side effects such as genitourinary symptoms, subcutaneous changes and reactions of the vaginal mucosa.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Chymotrypsin; Diarrhea; Drug Combinations; Endopeptidases; Erythema; Female; Humans; Middle Aged; Mucous Membrane; Papain; Prospective Studies; Radiation Injuries; Radiation-Protective Agents; Trypsin; Uterine Cervical Neoplasms; Vagina

Protease inhibitors have been known to exhibit anticarcinogenic activity in a variety of model systems, although the biological target(s) and mechanism remain enigmatic. Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity (NCLPA), which appears to be involved in transformation in several different experimental models, is significantly elevated in keratinocytes infected with high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic raft cultures, which is specific for cells infected with high-risk HPV types, using a chloromethyl ketone inhibitor previously shown to be relatively selective for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent of any alterations in the NCLPA. This finding has clear implications for the development of novel therapeutics specifically targeted to cervical dysplasias with HPV-infected cells.

Topics: Amino Acid Chloromethyl Ketones; Carcinoma; Cell Culture Techniques; Cell Nucleus; Cell Proliferation; Cells, Cultured; Chymotrypsin; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Female; Genome, Viral; Humans; Keratinocytes; Male; Oligopeptides; Papillomaviridae; Papillomavirus Infections; Peptide Hydrolases; Protease Inhibitors; Uterine Cervical Neoplasms

The immunologic reactivity of glycoprotein antigens extractable from individual, histologically different ovarian and uterine cancers was studied taking into account their relationship with carcinoembryonic antigen (CEA), nonspecific cross-reacting antigen (NCA), alpha-feto-protein (AFP), and alpha-1-antichymotrypsin. All studies were performed using specific immune sera against perchloric acid (PCA) extracts of ovarian mucinous cystadenocarcinoma (anti-PCA-CaOm) and cervical squamous cell carcinoma (anti-PCA-CaCx), and antisera against the reference antigens mentioned above. A considerable antigenic heterogeneity and the existence of several immunologically related antigenic systems were found: 1) CEA-like antigens; 2) NCA-type antigens; 3) an antigen different from CEA and NCA present in ovarian mucinous adenocarcinomas and often cross-reacting, but not identical with respective antigens of uterine body and cervical carcinomas; 4) an antigen reacting with anti-alpha-1-anti-chymotrypsin serum; and 5) an antigen reacting with anti-AFP serum.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; alpha-Fetoproteins; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Chymotrypsin; Cross Reactions; Cystadenocarcinoma; Female; Genital Neoplasms, Female; Glycoproteins; Humans; Immune Sera; Immunologic Techniques; Ovarian Neoplasms; Tissue Extracts; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: alpha 1-Antichymotrypsin; Carrier Proteins; Chymotrypsin; DNA-Binding Proteins; Female; Humans; Immunoglobulin M; Molecular Weight; Neoplasm Proteins; Ovarian Neoplasms; Uterine Cervical Neoplasms

Topics: Aged; Anti-Inflammatory Agents; Bromelains; Chymotrypsin; Deoxyribonucleases; Female; Fibrinolysin; Genital Diseases, Female; Humans; Inflammation; Mastitis; Middle Aged; Oxyphenbutazone; Pregnancy; Uterine Cervical Neoplasms