Cancer of the anus.

Cancers of the anus, whether keratinizing squamous, nonkeratinizing, clear-cell, or melanoma, are infrequent neoplasms. Small keratinizing (<4 cm2) with no deep invasion can be controlled by local excision or laser ablation, but larger ones may be treated by chemoirradiation, restricting abdominoperineal resection to recurrences. Neither melanomas nor clear-cell cancers are curable, and local control is the surgical objective.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

Purpose: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN.

Adenovirus-mediated E2F-1 gene transfer induces an apoptotic response in human gastric carcinoma cells that is enhanced by cyclin dependent kinase inhibitors.

E2F -1 is a transcription factor that regulates cell cycle progression into S-phase. Deregulation of E2F-1 activity has been associated with cellular commitment to apoptosis. Also critical in the regulation of S-phase are the actions of the cyclin dependent kinases, Cdk2 and cdc2.

Primary squamous cell carcinoma of the breast presenting as a breast abscess.

Primary squamous cell carcinoma (SCC) of the breast is a very rare neoplasm, with only 75 cases reported in the English literature. Herein, we report four new cases and discuss the diagnostic and therapeutic challenges of this unusual tumor in a retrospective review of all cases of SCC of the breast at our institution from 1990 to 1998. Four patients with breast SCC were identified, with a mean age of 70 years.

Bcl-2 inhibits early apoptotic events and reveals post-mitotic multinucleation without affecting cell cycle arrest in human epithelial tumor cells exposed to etoposide.

Unlabelled: Defective apoptotic mechanisms are considered to play a role in both the development of malignancy and resistance to chemotherapeutic drugs. The Bcl-2 family of proteins regulate the cellular commitment to survive or die when challenged with various apoptotic stimuli.

Purpose: The purpose of this study was to identify the point at which Bcl-2 interrupts the apoptotic cascade initiated following exposure of human tumor cells to etoposide.

Improvement in the prognosis of breast cancer from 1965 to 1984.

Purpose: The prognosis of breast cancer has improved over the past three decades. It is uncertain, however, whether this improvement results from an increase in the cure rate, extension of the life span of uncured patients, or some combination.

Methods: From the Connecticut Tumor Registry, we obtained data on 25,091 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer who were diagnosed over the two decades between 1965 and 1984, with follow-up through 1993.

A region within murine chromosome 7F4, syntenic to the human 11q13 amplicon, is frequently amplified in 4NQO-induced oral cavity tumors.

Our previous reports have shown that two thirds of 4-nitroquinoline-1-oxide (4NQO)-induced murine oral squamous cell carcinomas (SCC) have Hras1 mutations. Loss of heterozygosity (LOH) involving the distal portion of chromosome (Chr) 7 occurred in half of the tumors with Hras1 mutations. Here, we demonstrate that five of six tumors with LOH have 4-8-fold amplification involving the distal portion of Chr 7 (7F4).

Potentiation of etoposide-induced apoptosis by staurosporine in human tumor cells is associated with events downstream of DNA-protein complex formation.

Unlabelled: Protein kinase inhibitors have demonstrated potential for use in the therapy of human cancers, in particular leukemia. Staurosporine, a protein kinase inhibitor with broad specificity, enhances the cytotoxic effects of various antitumor agents with different modes of action. The topoisomerase II inhibitor, etoposide, has shown clinical activity against a wide range of tumor types.

Frequent DNA polymorphisms exist in inbred CBA/J and C3H/HeN mice.

Although occasional DNA polymorphisms have been observed in inbred mice, CBA/J and C3H/HeN mice have two microsatellite alleles at over 1/3 of microsatellite loci tested. Since DNA polymorphisms were not detected in DBA/2J, C57BL/6J, and BALB/cJ, the frequency of microsatellite polymorphisms appears to be strain specific. Thus, genetic studies in inbred mice require testing for preexisting polymorphisms.

Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival.

The Bcl-2 oncoprotein, which is expressed in a variety of human malignancies, blocks apoptosis induced by chemotherapeutic drugs, including the topoisomerase II inhibitor, etoposide. To determine the significance of Bcl-2 in etoposide-induced death of human epithelial tumor cells, HeLa S3 cells were transfected with human bcl-2 cDNA in the pSFFV expression vector, and stable Bcl-2-expressing clones established. In agreement with previous studies, Bcl-2 inhibited loss of cell viability (by trypan blue exclusion), the appearance of morphologically apoptotic cells, and the amount of low molecular weight DNA extracted after etoposide exposure (25 microns, 4 h).

Chemical modification of normal tissue damage induced by photodynamic therapy.

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1).

The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice.

IL-2 mediates the regression of certain malignancies, but clinical use is limited because of associated toxicities, including parenchymal lymphocytic infiltration with multiple organ failure. Secondarily induced cytokines are important mediators of IL-2 toxicity and IL-2-induced lymphocyte-endothelial adherence and trafficking. The recently discovered C-C chemokines, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1alpha, have also been implicated in lymphocytic migration.

Concentration-dependent differences in the mechanisms by which caffeine potentiates etoposide cytotoxicity in HeLa cells.

Morphological examination of HeLa cells exposed to etoposide for 1 h revealed two distinct modes of death: (a) within 6 h of drug removal, shrunken cells appeared which contained vacuolated cytoplasm and regions of intense chromatin staining, consistent with apoptosis; and (b) concomitant with release from G2 arrest, enlarged cells appeared which contained evenly staining nuclear fragments, consistent with mitotic death. The methylxanthine, caffeine, enhanced cytotoxicity in a concentration-dependent manner when applied for 24 h following etoposide exposure. One mM caffeine alleviated etoposide-induced G2 arrest and increased the incidence of mitotic death, accounting for the potentiation of cytotoxicity.

Squamous cell carcinoma of the upper aerodigestive tract in patients 40 years of age and younger.

Oral squamous cell carcinoma in patients 40 years of age and younger has been noted to be infrequent. The incidence is not as noticeable because the majority of oral cancers are diagnosed during the later decades of life. This study was undertaken to evaluate the incidence, site predilection, etiologic factors, and modes of treatment and to compare these results with available data on this topic.

Pentoxifylline inhibits interleukin-2-induced toxicity in C57BL/6 mice but preserves antitumor efficacy.

Interleukin 2 (IL-2) mediates the regression of metastatic cancer but clinical use has been limited due to associated toxicities. Tumor necrosis factor (TNF) is an important mediator of IL-2 toxicity and may have a limited role in IL-2 antitumor efficacy. Because pentoxifylline (PTXF) inhibits TNF production, we hypothesized that PTXF would ameliorate IL-2 toxicity without compromising antitumor efficacy.

An update on incision for ilioinguinal lymph node dissection.

The wound morbidity after ilioinguinal lymph node dissections can be significantly reduced by precise planning of both the incision and the extent of flap elevation. Flap elevation extends no farther than the edges of the quadrilateral block of Anson, and exposure is best obtained with a bipedicle incision with broad-based pedicles. The broad bases ensure the greatest possibility for the sustentation of the flaps by the remaining microcirculation.

Inhibition of p34cdc2 kinase activation, p34cdc2 tyrosine dephosphorylation, and mitotic progression in Chinese hamster ovary cells exposed to etoposide.

p34cdc2 kinase, an enzyme essential for mitosis in mammalian cells, may play a role in etoposide-induced G2 phase arrest of Chinese hamster ovary cells. In this study, etoposide is shown to cause inhibition of a specific p34cdc2 kinase activation pathway, that of tyrosine dephosphorylation. Exposure of asynchronously dividing cells to etoposide caused a simultaneous rapid decline of both mitotic index and p34cdc2 kinase activity, suggesting that the kinase was not activated and that the arrest point was in late G2 phase.

Pattern of growth factor, proto-oncogene and carcinoembryonic antigen gene expression in human colorectal carcinoma cell lines.

The aim of the present study was to examine whether the expression of growth factor genes, proto-oncogenes and carcinoembryonic antigen (CEA) gene in human colorectal cancer cell lines was related to their clinicobiological behavior. A significant variability among cell lines was detected for both insulin-like growth factor II and transforming growth factor beta gene message. Detectable levels of c-myc, Her-2, c-myb, K-ras and EGF receptor mRNA were found in most cell lines, whereas only 1/11 and 2/11 cell lines were positive for N-myc and c-sis message, respectively.

Medical and legal implications of screening and follow-up procedures for breast cancer.

Grievances result from false expectations on the part of both practitioners and patients when a disease treatment problem is unsolved because of biological variations in the disease itself. Widely publicized screening and follow-up recommendations are often the source of the grievances. Even when recommendations are followed exactly, bad outcomes are still associated with incurable cancer even though a fatal outcome is inevitable.

Phase II study of multiple daily fractionations in the palliation of advanced pelvic malignancies: preliminary report of RTOG 8502.

This Phase II protocol was designed around the format of a previously reported study for the palliation of advanced pelvic malignancies (RTOG 7905). The large dose per fraction (1000 cGy) of the first study unexpectedly demonstrated frequent late gastrointestinal toxicity and was replaced in the present study by 2 days of twice daily fractionation (370 cGy/fraction totaling 1480 cGy/course) based on linear quadratic consideration of acute and late toxicities. The interval between courses of 4 weeks was retained and the total dose for three courses was 4440 cGy.

Differential protection of radiation-induced DNA single-strand breaks and cell survival by solcoseryl.

V79 Chinese hamster cells were studied in vitro for modification of cobalt-60 gamma radiation effects by solcoseryl. This treatment did not modify cell survival but did protect against DNA single-strand breaks.

Influence of column length and pore size on high-performance ion-exchange chromatography of estrogen and progestin receptors.

A high-performance liquid chromatographic (HPLC) procedure has been evaluated to establish a routine test in the clinical laboratory for measuring the profiles of estrogen and progestin receptor isoforms in human breast and endometrial tumors. This procedure will be used to determine if there is a relationship between particular isoform profiles and response to various endocrine therapies. Evaluation of various HPLC modes has shown that high-performance ion-exchange chromatography (HPIEC) with silica-based anion exchangers offers a promising approach.