ABSTRACT
We report the rare occurrence of a small bowel perforation secondary to a metastatic cutaneous squamous cell carcinoma (cSCC). A 70-year-old woman, who had previously undergone renal transplantation, presented with severe, sudden-onset abdominal pain. She was peritonitic on initial examination, with evidence of free intra-abdominal air on radiographic imaging. During an exploratory laparotomy, she was found to have a perforated jejunum secondary to disseminated metastases seen throughout her peritoneum. Following histopathological analysis, as well as further imaging studies, the primary malignancy was eventually identified as a cSCC on her upper back. Palliative care was started and the patient died 8â weeks following her initial presentation.
Subject(s)
Carcinoma, Squamous Cell/secondary , Intestinal Perforation/etiology , Jejunal Diseases/etiology , Peritoneal Neoplasms/secondary , Skin Neoplasms/diagnosis , Abdominal Pain/etiology , Aged , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Early Detection of Cancer , Endoscopy, Gastrointestinal , Fatal Outcome , Female , Humans , Immunosuppression Therapy , Kidney Transplantation , Peritoneal Neoplasms/diagnosis , Positron-Emission Tomography , Postoperative Complications , Tomography, X-Ray ComputedABSTRACT
Trastuzumab (Herceptin) is the first monoclonal antibody to be approved for the treatment of a solid tumour and is directed against the c-erb-B2 receptor. c-erb-B2 is a member of the epidermal growth factor family and approximately 25% of breast cancers express such receptors, which appear to confer a poorer prognosis and may be an indicator of resistance to cytotoxic chemotherapy. This review assesses the mechanisms of action of trastuzumab, discusses the measurement of the HER-2/neu gene and its products, and describes the preclinical and clinical studies that have been instrumental to date in the emergence of trastuzumab in clinical practice.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Animals , Antibodies, Monoclonal, Humanized , Clinical Trials as Topic , Genes, erbB-2/genetics , Humans , Receptor, ErbB-2/immunology , TrastuzumabABSTRACT
An endopeptidase has been purified from Lactococcus lactis subsp. cremoris SK11. The enzyme is a 70 kDa monomer, strongly inhibited by the metalloproteinase inhibitors 1,10-phenanthroline and phosphoramidon but relatively insensitive to EDTA. It is not significantly inhibited by the thiol enzyme inhibitor p-chloromercuribenzoate nor by the serine protease inhibitor phenylmethylsulphonyl fluoride. The action of the endopeptidase in catalysing the hydrolysis of several peptide hormones has been studied and the hydrolysis products identified by sequence analysis. The enzyme catalyses hydrolysis of peptide bonds in which a hydrophobic amino acid (most commonly a Phe or Leu) residue occupies the position immediately C-terminal to the hydrolysed bond. It thus has a specificity very similar to that of thermolysin. Two of the oligopeptides produced during the early stages of beta-casein digestion by the lactococcal cell-wall proteinases were hydrolysed by the endopeptidase, the others were resistant to hydrolysis. Cell fractionation studies have shown that the distribution of endopeptidase activity between the different cell fractions is the same as that of the intracellular marker enzyme fructose bisphosphate aldolase, and thus indicate a cytoplasmic location for the enzyme. These observations argue against a role for this enzyme in the early stages of casein breakdown by the lactococcal proteolytic system.
