Long-standing complete remission following mitomycin-C/vinblastine chemotherapy for cutaneous and lymph node metastases from breast cancer resistant to multiple chemotherapy and hormonal lines and extensive radiotherapy: an unusual case.

Widespread cutaneous and lymph nodes recurrence in breast cancer is regarded as therapy-resistant disease. We describe a 50-year-old patient who presented with treatment-refractory disease following multiple lines of chemo- and hormonotherapy, photodynamic therapy and radiotherapy, including re-irradiation to extended volumes of her chest, upper abdomen, back and regional lymph nodes. Following treatment with mitomycin-C (MMC)/vinblastine (VLB) alone, she entered sustained complete remission of 1-year duration without any side effects. A brief review of the current literature is also presented. The MMC/VLB combination might achieve reasonable response and improvement of quality life even in patients with advanced breast cancer.

Trauma as an etiologic factor of primary bone lymphoma: a report of 4 cases.

Primary bone lymphoma (PBL) is a rare entity. Nevertheless, very high long-term complete remission and survival rates following adriamycin-based chemotherapy alone or combined with involved-field radiation therapy have been reported. While the etiology is unknown, factors comprising local or general immunocompromised states have been suggested. Sporadic cases of local trauma followed by the emergence of primary bone lymphoma have been described. We describe 4 patients who developed primary bone lymphoma following direct trauma to a specific bone area. All 4 are alive with no evidence of disease after being treated with a combined chemo-radiotherapy regimen.

Neutropenic enterocolitis: a rare presenting complication of acute leukemia.

Neutropenic enterocolitis is a necrotizing inflammatory process with intramural infection that occurs predominantly in neutropenic patients. This syndrome is most frequently observed after chemotherapy for hematologic and solid tissue malignancies, but it can also be observed in a number of other clinical settings as well. Neutropenic enterocolitis can be a rare presenting complication of acute leukemia. We report a case of acute lymphoblastic leukemia that presented with abdominal pain due to neutropenic enterocolitis. The diagnostic and treatment challenges associated with this manner of presentation are discussed.

Palisaded angioleiomyoma.

BACKGROUND: We report a case of a palisaded angioleiomyoma, a histopathologic variant of angioleiomyoma with prominent Verocay body formation. RESULTS: A healthy 31-year-old male requested removal of a subcutaneous nodule on the back of his head. The striking Verocay-like body formation of this tumor led to an initial frozen section diagnosis of neurilemoma. On hematoxylin and eosin staining, areas consistent with an angioleiomyoma were found as well. Immunohistochemistry gave positive reactions for actin and desmin, but was negative for S-100. CONCLUSIONS: To our knowledge this morphologic pattern in an angioleiomyoma has not been previously described. Palisaded angioleiomyoma should be added to the ever-expanding list of tumors that demonstrate nuclear palisades.

The study of gemcitabine in combination with other chemotherapeutic agents as an effective treatment for prostate cancer.

BACKGROUND: Gemcitabine has demonstrated clinical activity against several common cancers. Our studies examine the ability of gemcitabine, both alone and in combination with other chemotherapeutic agents, to inhibit the in vitro and in vivo growth of several prostate cancer cell lines. MATERIALS AND METHODS: Cultures of LNCaP, PC-3 or MLL cells were exposed to either gemcitabine or other appropriate agents for specified amounts of time. Cells were lysed and nuclei counted utilizing a Coulter Counter. For in vivo experiments, animals were injected with 1 x 10(5) MLL cells subcutaneously into the right flank. Animals were treated as indicated for 14 days. Tumors were then excised, weighed and measured. RESULTS: In both human (PC-3 and LNCaP) and rat prostate (MLL) cancer cell lines our studies demonstrated gemcitabine had a strong effect in vitro, with an IC50 of approximately 500 nM in the human lines and 10 nM in MLL cells. In vivo, studies using the Dunning prostate cancer model in Copenhagen rats resulted in a dose response inhibition of tumor growth, with an 80% decrease in tumor size in rats treated with gemcitabine at 10 mg/kg. CONCLUSIONS: Our results demonstrated the potent activity of gemcitabine against prostate cancer in the Dunning rat model and suggest the addition of paclitaxel may not aid in this activity.

The effect of amiloride on the metastatic properties of prostate cancer in the Dunning rat model.

Most deaths from cancer result from the metastatic spread of the disease. The antidiuretic amiloride has been shown to inhibit tumor growth and metastasis in several tumor systems. The object of these studies was to examine the effect on the in vitro and in vivo tumor growth and metastasis in the MatLyLu subline of the Dunning model of rat prostate cancer. In vitro, amiloride was found to have cytotoxic effects only at high concentrations, with an IC50 of 100 microg/ml. In vitro analysis of the ability of amiloride to inhibit invasion of MLL cells demonstrated that this drug was ineffective at all concentrations examined. In vivo, amiloride did not inhibit tumor growth or metastases development. Our studies demonstrate that amiloride does not have activity in this model of prostate cancer and suggest it may not be an appropriate therapy for the treatment of prostate cancer.

Association of transcription factors with the nuclear matrix.

The nuclear matrix is the framework scaffolding of the nucleus and has been demonstrated to be an important component in a number of nuclear processes including transcription, replication, and RNA splicing and transport. In the interphase nucleus, DNA is specifically organized in a three-dimensional fashion. An example of this fact is that actively transcribed genes have been demonstrated to associate with the nuclear matrix. In this study, nuclear matrix proteins from various rat tissues, including two androgen-regulated tissues, the seminal vesicle and ventral prostate, were examined to determine if they contained proteins that associate with consensus binding sequences for several proteins involved in the regulation of transcription. Specific interactions were identified between proteins of the nuclear matrix and these transcriptional activator binding sequences. In addition, the sizes of the complexes binding to the DNA sequences appeared to vary in some of the tissues. These data support the concept that the nuclear matrix may serve as a support structure to bring together specific DNA sequences with factors involved in the regulation of gene expression.

Bladder cancer-associated nuclear matrix proteins.

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, including the regulation of DNA replication and gene expression. Previous investigations into prostate and breast cancer have revealed that nuclear matrix protein (NMP) composition undergoes alterations with transformation and that the nuclear matrix can serve as a marker for the malignant phenotype. In this study, we have identified NMPs with which it is possible to differentiate human bladder tumors from normal bladder epithelial cells. We examined the NMP composition of 17 matched tumor and normal samples from patients undergoing surgery for bladder cancer. We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples. Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cells lines examined (253j, UMUC-2, and T24). Therefore, we have demonstrated that nuclear matrix composition is able to differentiate bladder cancer from normal bladder tissue and may provide useful tools for early detection and recurrence of the disease. Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.

Psychological follow-up of women evaluated as oocyte donors.

Forty-five women were evaluated as candidates to donate oocytes to an infertile couple. Twenty-four women completed a cycle as oocyte donors. Follow-up data on donor satisfaction were obtained for 23 women. Ninety-one per cent were moderately to extremely satisfied with the experience and 74% would donate for another cycle if given the chance. Transient adverse psychological symptoms were reported by two donors but were resolved with medical or psychological treatment. Two women became pregnant soon after donation, one unintentionally. Psychological risk factors predicted donor candidates' decisions to participate and their compliance but were not predictive (within the group that completed a cycle) of donor satisfaction as follow-up or recipient pregnancy.

Establishment of an oocyte donor program. Donor screening and selection.

IVF with donated oocytes, followed by embryo placement in the uterus of a recipient who has been primed with exogenous steroids, is a successful treatment for special cases of infertility. Preliminary results indicate that the success rate in this situation is even greater than that usually seen with normal IVF (with placement of the embryos back into the uteri of the women from whom the oocytes were recovered). Although different sources for donated oocytes have been identified, the use of "excess" oocytes from IVF cycles and the attempted collection of oocytes at the time of otherwise indicated pelvic surgery have ethical and practical problems associated with their use. We have herein described the establishment of a successful program relying on anonymous volunteers who go through ovarian stimulation, monitoring, and oocyte recovery procedures solely to donate oocytes. The potential donors go through an exhaustive screening and education process before they are accepted in the program. Psychological evaluation of our potential donors indicated a great degree of turmoil in their backgrounds and a wide variety of motivations for actually participating. Despite the extensive educational and screening process, a substantial percentage of the donors did not complete a donation cycle, having either voluntarily withdrawn or been dropped because of lack of compliance. Further investigation of the psychological aspects of participating in such a program is certainly warranted. The use of donated oocytes to alleviate specific types of infertility is quite successful, but the application of this treatment is likely to be limited by the relative unavailability of suitable oocyte donors.

Hormonal regulation of human endometrial stromal cells in culture: an in vitro model for decidualization.

Stromal cells derived from proliferative or secretory human endometria, cultured in the absence of steroid hormones, grew as monolayers that showed only occasional areas of immunoreactive fibronectin and did not produce detectable levels of prolactin (PRL) or laminin. Treatment with physiological doses of estradiol and progesterone induced PRL production and stimulated cell proliferation, resulting in multilayering with an increase of the saturation density. Electron microscopy showed the development of gap junctions, whereas immunofluorescence revealed a dense pericellular matrix containing fibronectin and laminin. These findings show that human endometrial stromal cells in culture respond to physiological doses of ovarian hormones with ultrastructural, proliferative, and biochemical changes that are characteristic of decidualization in vivo. This culture system thus provides an in vitro model for human decidualization.

Gamete processing in an environmental chamber: effect on in vitro fertilization outcome.

A study of mouse gamete processing for in vitro fertilization (IVF) under various conditions showed that it is necessary to control the atmosphere if the temperature is raised from 22 degrees C to 37 degrees C. The data suggest that maximum IVF success is attained by processing the gametes at 37 degrees C, under an atmosphere of 5% O2 and 5% CO2, and overlaying the medium with silicone oil.

Increased human menopausal gonadotropin dose during the early follicular phase: effect on follicular recruitment and treatment outcome.

To investigate whether the provision of increased gonadotropins would enhance follicular recruitment and selection, women not responding (N = 18) to our standard clomiphene citrate (CC)-human menopausal gonadotropin (hMG) regimen were treated with increased hMG (treatment cycle II). Estradiol levels were higher in treatment cycle II and these differences were significant on days 8 and 9 (P less than or equal to 0.05 and P less than or equal to 0.03, respectively). On day 9, better follicular development was seen in cycle II (P less than or equal to 0.05). While none of the patients responded in cycle I, 10 of 18 responded in cycle II. Of the 10 responders, 2 conceived following in vitro fertilization and embryo placement. Increasing the dose of hMG improved the development of a cohort of follicles so that aspiration and possible pregnancy were achieved in women who were previously unresponsive to therapy.

Combined clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in a fixed schedule for follicular recruitment during in vitro fertilization: effects on premature luteinizing hormone (LH) surges.

Recognizing the association between plasma progesterone (P) and an imminent LH surge, we investigated the frequency of P elevation in our stimulation protocol (clomiphene citrate-human menopausal gonadotropins). P was measured retrospectively on the day before, the day of, and the day after human chorionic gonadotropin hCG administration. The means +/- 2 standard deviations for P were as follows: day before hCG, 0.58 +/- 0.86; day of hCG, 0.64 +/- 0.56; and day after hCG, 1.47 +/- 1.22. Seven patients (8%) had P levels greater than 2 SD above the mean. Significant P elevations prior to hCG are infrequent with this protocol, and in the few patients with raised P a trend toward lowered fertilization was noted. The low incidence of P elevation may be secondary to the administration of hCG in a timely manner on the sixth day of estradiol (E2) rise.