mTOR inhibitors show promising in vitro activity in bladder cancer and head and neck squamous cell carcinoma.

Bladder cancer and head and neck squamous cell carcinoma (HNSCC) are frequent but lack efficient therapies especially in advanced disease. Almost no studies on mTOR function and inhibition in these tumor entities have been reported. We examined the gene and protein expression levels of mTOR and its activated form (pmTOR) in three human bladder carcinoma cell lines (RT-4, T24, EJ28) and three HNSCC cell lines (PCI-1, PCI-13, BHY).

In vivo studies on the availability and toxicity of antisense oligonucleotides in bladder cancer.

Background: The urinary bladder is an ideal organ for topical treatment. A substantial number of bladder cancer patients are resistant to conventional intravesical therapy. In search of new agents, antisense oligonucleotides (AS-ON) may be interesting candidates.

Inhibition of bcl-2 enhances the efficacy of chemotherapy in renal cell carcinoma.

Objectives: Renal cell cancer (RCC) is highly resistant to chemotherapy. Increased expression of the antiapoptotic gene bcl-2 in tumors is known to be associated with poor responses to systemic treatment of cancer. Down-regulation of bcl-2 expression using antisense oligonucleotides (asON) has been shown to increase chemosensitivity in clinical phase I-III studies with various cancers.

Cytogenetic tetraclonality in a rare spindle cell variant of an anaplastic carcinoma of the thyroid.

We report a case of an unusual anaplastic carcinoma with spindle cell differentiation in an 85-year-old patient. Although the tumor showed sarcoma-like features its occurrence in the thyroid of an elderly person supported the diagnosis of an anaplastic carcinoma. This diagnosis is also supported by the results of cytogenetic studies that revealed four independent clones.

Chromosomal translocations affecting 12q14-15 but not deletions of the long arm of chromosome 7 associated with a growth advantage of uterine smooth muscle cells.

Cytogenetically, uterine leiomyomata are the best investigated human tumours. The most frequent clonal abnormalities are structural rearrangements involving 12q14-15 and deletions of part of the long arm of chromosome 7. The present study investigated a possible growth advantage conferred by these abnormalities, when compared with myomata having an apparently normal karyotype.

Structural abnormalities of chromosome 2 in benign thyroid tumors. Three new cases and review of the literature.

Here we report our cytogenetic findings on three cases of nodular goiter, all showing structural clonal abnormalities of chromosome 2. In the first case, we found a t(2;3)(q21;q27 or q28) in two nodules of the same patient. The second case revealed a t(2;20;3)(p21;q11.

Follicular thyroid carcinoma: chromosome analysis of 19 cases.

Short-term cultures of 19 follicular thyroid carcinomas were examined cytogenetically. Clonal chromosomal changes were detected in 12 tumors. Two follicular carcinomas had only numerical alterations: one with a hyperdiploid karyotype with trisomies/polysomies of chromosomes 7 and 12, similar to the karyotypes previously identified in a sub-group of benign thyroid lesions, and the other with monosomy 20.

Cytogenetic investigations of 340 thyroid hyperplasias and adenomas revealing correlations between cytogenetic findings and histology.

Cytogenetic analyses were performed on 340 follicular thyroid adenomas and goiters after short-term culture. Clonal chromosomal changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases).

[Cytogenetic changes in benign thyroid gland hyperplasias and adenomas correlated with histology].

In order to elucidate cytogenetic changes associated with the development of benign growth of follicular epithelial cells of the thyroid, cytogenetic analyses were performed on 340 follicular thyroid adenomas and goiters after short-term culture. Clonal chromosome changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases).

An endometrial polyp with a rearrangement of HMGI-C underlying a complex cytogenetic rearrangement involving chromosomes 2 and 12.

Cytogenetic studies of an endometrial polyp of an 82-year-old patient revealed a karyotype 46,XX,der(2)inv(2)(p25q21)ins(2;12)(p25;q13q14)t(2;12)(q21; q15),der(12)del(12)(q13q14)del(12)(q15). By fluorescence in situ hybridization (FISH) we found the chromosome 12 translocation breakpoint to be mapping within the third intron of the HMGI-C gene also harboring the breakpoints of translocations involving 12q15 seen in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondroid hamartomas.

Deletions of the short arm of chromosome 2 characterize a new cytogenetic subgroup of benign thyroid tumors.

Cytogenetic studies of thyroid hyperplasias and adenomas have shown that besides cases with an apparently normal karyotype different groups of cytogenetic abnormalities exist. Herein we describe the cytogenetic analyses of two benign thyroid tumors with deletions of the short arm of chromosome 2. A similar case has been described previously.

Structural aberrations of chromosome 6 in three uterine smooth muscle tumors.

Clonal karyotypic alterations of chromosome 6 in three uterine smooth muscle tumors are reported. In all cases an apparently identical breakpoint on the short arm of chromosome 6 was found. Two cases displayed the histologic features of cell-rich myomas with severe nuclear atypia but no clear evidence for malignancy.

Cytogenetic biclonality corresponding to multiphasic differentiation in an atypical thyroid adenoma.

Cytogenetic aberrations have been described in about 30% of benign thyroid tumors, but their role for tumorigenesis or progression has not yet been elucidated. We describe the cytogenetic analyses in a thyroid adenoma with two different clonal cytogenetic stemlines: 45,XX,der(1)t(1;14)(p13;q11.2-q(13),t(5;12)(q11.

A characteristic sequence of trisomies starting with trisomy 7 in benign thyroid tumors.

The cytogenetic results from a series of 113 thyroid hyperplasias and adenomas are reported; 15 showed clonal karyotypic alterations. In addition to a group showing translocations involving 19q13, another subset of lesions characterized by polysomies can be found. Based on our own cases belonging to this subset and a review of the cases reported in the literature, we conclude that the characteristic feature of this group is a sequence that always starts with trisomy 7, but that sometimes even leads to chromosome numbers in the hypertriploid range.

[Cytogenetic subtyping of 139 uterine leiomyoma].

A cytogenetic study of 139 uterine leiomyomas of 70 patients is presented. 26 of the tumours failed to grow, 87 showed an apparently normal karyotype and 26 tumours were characterised by clonal aberrations. In 5 tumours, a numerical change was the only abnormality, including 2 tumours with a trisomy 12.

Pleomorphic adenoma cells vary in their susceptibility to SV40 transformation depending on the initial karyotype.

Chromosomal aberrations involving 8q12 or 12q13-15 characterize two cytogenetic subgroups of salivary gland pleomorphic adenomas. As the tumors of the two groups differ in their clinical and histologic characteristics, we decided to determine their susceptibility to SV40 transformation. We transfected cell cultures from 13 adenomas with aberrations involving 8q12 and from seven adenomas with involvement of 12q13-15 using an SV40 plasmid coding for the early region of the viral genome.

Aberrations of chromosome 19. Do they characterize a subtype of benign thyroid adenomas?

We describe the cytogenetic findings in two benign thyroid hyperplasias with aberrations of chromosome 19. In the first patient, two of four nodules showed identical translocations involving chromosome 19 and 22: 46,XX,der(19)t(19;?)(q13;?),der(22)t(22;?)(q12;?), the remaining nodules had an apparently normal karyotype. Two nodules from a second patient were karyotyped.

Deletion of part of the long arm of chromosome 13 as the only karyotypic aberration in a follicular thyroid adenoma.

A follicular thyroid adenoma is described showing a del(13)(q14) as the only karyotypicabnormality. The karyotypic similarities to another benign tumor, the lipoma, are discussed.

Leiomyoma cells with 12q15 aberrations can be transformed in vitro and show a relatively stable karyotype during precrisis period.

Tumor cells from three uterine leiomyomas showing translocations involving 12q14-15 were transformed by transfection using the "early regions" of the SV40 genome. The cells had a higher proliferative capacity, were able to form colonies in soft agar, and showed an increased growth potential. Karyotype analyses of these transformed leiomyoma cells showed that the cells had retained the initial t(12;14) and t(12;15).