estramustine and Skin-Neoplasms

Clinically approved anticancer drug estramustine mediates its function by impairing microtubule polymerization. However, the low aqueous solubility and high toxicity limit its anticancer activity via the oral route. Previously, efforts have been made to develop an enhanced water soluble form of estramustine as estramustine phosphate (EM) but acidic gastrointestinal pH breaks the phosphate derivative via oral administration. As an alternative approach, we have made an effort to enhance solubility and minimize toxicity in vivo by conjugating EM to a poly(amidoamine) (PAMAM) dendrimer, which generated the sustained release of dendrimer conjugate (DEM). To the best of our knowledge, for the first time, we report the direct proof of the nano-crystalline 'DenDot' of DEM on TEM image. The toxicity study showed that both EM and DEM were nontoxic up to 20mg/kg. A comparative anti-papilloma study was also performed with EM and dendrimer conjugates (DEM) using a two-stage mouse skin carcinogenesis model. We found that DEM was more effective in inhibiting skin tumor formation than EM. Histopathology and immunohistochemistry studies further indicated that DEM treatment increased cell apoptosis, and reduced epithelial hyperplasia, cell proliferation and inflammation in skin tissues of mice. In addition, the synthetic DEM conjugate inhibited skin tumor progression more effectively than EM.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Apoptosis; Carcinogens; Cell Proliferation; Dendrimers; Estramustine; Female; Intestines; Kidney; Liver; Mice; Nanoparticles; Papilloma; Skin Neoplasms; Stomach; Tetradecanoylphorbol Acetate

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone; Diphosphonates; Estramustine; Fatal Outcome; Flutamide; Humans; Imidazoles; Ketoconazole; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radionuclide Imaging; Skin Neoplasms; Triptorelin Pamoate; Zoledronic Acid

Carcinoma of the prostate gland is the second most frequent malignancy in males, accounting for 17% of cancer in men; between a third and one-half of these patients will have distant metastases at onset, but rarely cutaneous. We now report a case of prostatic adenocarcinoma with such metastases involving the right nipple and periareolar skin, overlying an area of hormone-induced gynaecomastia.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Estramustine; Fatal Outcome; Gynecomastia; Humans; Male; Prostatic Neoplasms; Skin Neoplasms

Chemotherapy was administered in the immediate postoperative period to seventy patients (52 with melanomas and 18 with sarcomas) after a total of eighty-seven major operations, with no morbidity or mortality traceable to the chemotherapy. There was no apparent interference with wound healing or what would be considered a normal postoperative course. Fourteen of these patients (5 with melanomas and 9 with sarcomas) received a combination of radiation anc chemotherapy initiated in the postoperative period, and it was tolerated well. This combination appears to be safe, provided the field of radiation is not so large that is may add significantly to the myelosuppressive effect of chemotherapy and the dosage of concomitantly administered radiopotentiating agent(s) is reduced. Sixteen patients had Bacillus Calmette-Gúerin (BCG) immunotherapy in the immediate postoperative period without complications. This policy of a tight interweaving of modalities is safe, has the theoretic advantage of an earlier concerted attack on microscopic residual tumor, and appears particularly promising in sarcomas.

Topics: BCG Vaccine; Dacarbazine; Estramustine; Humans; Melanoma; Melphalan; Radiotherapy Dosage; Sarcoma; Skin Neoplasms