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J H Kearsley

Publications and source records attributed to J H Kearsley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Radiation sensitivity of Merkel cell carcinoma cell lines.

PURPOSE: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. METHODS AND MATERIALS: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after gamma irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. RESULTS: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to gamma irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. CONCLUSION: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution.

Carcinoma, Merkel Cell↗
PubMed1995

The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma.

PURPOSE: To determine the role of postoperative radiation therapy in the treatment of Merkel cell carcinoma (MCC). METHODS AND MATERIALS: Eighty patients with MCC of the skin were treated with curative intent at the Queensland Radium Institute between 1981 and 1991. Fifty-one patients (63.7%) were referred after initial biopsy for further treatment and 29 patients (36.3%) were referred with locally recurrent disease following primary surgery elsewhere. Thirteen patients (16.3%) presented with nodal disease without a clinically definable primary skin lesion. RESULTS: Of the 80 patients, 38 had undergone surgery (S) alone, 34 surgery plus radiotherapy (S + RT), 7 RT after incomplete S, and 1 patient had chemotherapy (CT) plus RT. Overall survival at 36 months for all patients was 68%. All of the 38 patients treated with S alone relapsed. The median time to recurrence was 5.5 months. Ten of the 34 patients treated with S + RT relapsed. The median time to recurrence was 16.5 months. Of the 80 patients, 55 have relapsed after primary treatment, 25 have developed systemic metastases, and 26 patients have died as a direct result of MCC. CONCLUSION: Our large series confirms earlier reports from this Institute and highlights the importance of S + RT over S alone in preventing local recurrence of this highly malignant skin cancer.

Adult↗
PubMed1995

Characterisation of four Merkel cell carcinoma adherent cell lines.

We have previously described the establishment of a number of cell lines from Merkel cell carcinoma (MCC), also known as small cell cancer of the skin or neuroendocrine carcinoma of the skin. These cells, all of which grew as suspension cultures, were found to resemble small cell lung cancer (SCLC) lines types 1, 2 and 3 by their morphology and growth characteristics. We now report 4 more MCC cell lines which resemble the SCLC type 4 cell lines in that they grow as adherent monolayers. These MCC lines would belong to the variant subgroup as they no longer express most neuroendocrine markers, grow at low cell density and have population doubling times of 1-5 days in contrast to the MCC suspension lines which have doubling times of 6-12 days. MCC14/1 and MCC14/2 were established from the same metastatic node and would appear to represent 2 clones of the tumour which differ in morphology, histochemical markers and DNA content. We present details of the morphology, DNA content and immunohistochemistry of these 4 lines and compare their growth patterns with those of SCLC and MCC lines which grow in suspension.

Aged↗
PubMed1995

Post-orchidectomy radiation therapy alone for patients with early stage non-seminomatous germ cell tumours of the testis.

The aim of this study was to review the patterns of disease relapse and survival outcomes for patients treated post-orchidectomy with radiotherapy for early stage (I and IIA) non-seminomatous germ cell tumors of the testis (NSGCT). The clinical records were reviewed of 117 men consecutively treated at the Queensland Radium Institute from 1960-90 (inclusive) for stage I or IIA NSGCT. A total of 108 patients received radiotherapy to the para-aortic nodes and ipsilateral hemipelvis following orchidectomy; nine patients received radiotherapy to the para-aortic nodes and whole pelvis. Twenty-two of 99 (22.2%) stage I and eight of 18 (44.4%) stage IIA patients relapsed following definitive radiotherapy. The 5 year overall and recurrence-free survivals were 84 and 75%, respectively. Factors associated with a significantly worse outcome included: (i) patients with stage IIA disease; (ii) the presence of undifferentiated elements in the operative specimen; (iii) a primary tumor < 5 cm size; and (iv) treatment given prior to 1979. Given the unsatisfactory recurrence rate following radiation therapy alone and the availability of cisplatin-based chemotherapy regimens, it is recommended that radiation therapy alone for patients with early stage NSGCT be abandoned in favour of other management strategies.

Adult↗
PubMed1995

Familial Klippel-Feil syndrome and paracentric inversion inv(8)(q22.2q23.3).

Klippel-Feil Syndrome (KFS) is characterized by congenital vertebral fusion believed to result from faulty segmentation along the embryo's developing axis. KFS appears to be a heterogeneous disease often associated with craniofacial malformation. Here we provide the first evidence of a familial KFS gene locus on 8q, where an inv(8)(q22.2q23.3) has been found segregating with congenital vertebral fusion. The four-generation KF2-01 family present with dominant form of the KFS where the sequence of vertebral fusion was confined to the cervical spine (always including the C2-3 fusion and reduced expression of the C4-5 and C6-7 fusions) in association with malformation of laryngeal cartilages and mild-to-severe vocal impairment.

Chromosome Inversion↗
PubMed1994

Post-orchidectomy radiation therapy for patients with stage I seminoma of the testis.

The outcome of radiotherapy in patients with stage I testicular seminoma was evaluated. During the period 1960-89 (inclusive) 270 patients with stage I seminoma of the testis received radiotherapy to the para-aortic nodes and ipsilateral hemipelvis following radical orchidectomy. Two hundred and fifty seven patients (95.2%) received a minimum tumour dose of 30Gy in 20 daily fractions using 4-6 MV photons. The 5 year overall and recurrence-free survival rates were 97 and 95%, respectively. Only eight of the 270 patients relapsed and three were cured with 'salvage' therapies. Of the 11 patients who died, four deaths (36%) were the result of uncontrolled testicular cancer, six (55%) intercurrent illness and one (9%) the result of attempted salvage. Patients staged and treated prior to 1979 had a significantly worse disease-free survival compared to patients treated during and after 1979. As side effects were negligible, it was concluded that radiotherapy for stage I seminoma provides excellent cure rates. The difficulties arranging a 'surveillance' programme in so large a State as Queensland are discussed.

Adolescent↗
PubMed1994

Molecular biology and the radiation oncologist.

An overview is provided of several recent advances in our understanding of the molecular events that occur when cells are exposed to ionizing radiation. A basic knowledge of molecular radiobiology is necessary so that the radiation oncologist can (i) screen cancer patients for an abnormally reduced or exaggerated response to radiotherapy; and (ii) devise novel ways to counter the molecular pathways that sustain malignant progression.

Animals↗
PubMed1994

Some basic guidelines in the use of chemotherapy for patients with incurable malignancy.

The increasing use of cytotoxic chemotherapy for patients with incurable malignancy has raised a number of practical and ethical dilemmas for health care workers in the fields of oncology and palliative medicine. This paper addresses some of these issues and attempts to suggest basic principles which may contribute to the successful use of palliative chemotherapy.

Antiemetics↗
PubMed1993

Characterization of cell lines established from Merkel-cell ("small-cell") carcinoma of the skin.

Six cell lines have been established from different biopsies of the rare small-cell skin cancer of neuro-endocrine origin known as Merkel-cell carcinoma (MCC). These were established from metastatic lesions and have now been in culture for periods varying from 1 to 3 years. All lines grow as suspension cultures and exhibit typical MCC cytological features of small round cells with little cytoplasm, round nuclei and tight junctions. There was variation in the number and size of nucleoli and dense-core granules. We present details of their immunohistochemistry and growth characteristics in culture. The latter were similar to small-cell lung-cancer (SCLC) lines and can be subdivided, by their appearance, into type I, type II and type III in the same way as SCLC lines. This classification may be of significance for the prognosis and management of MCC.

Carcinoma, Merkel Cell↗
PubMed1993

Chromosomes 1, 11, and 13 are frequently involved in karyotypic abnormalities in metastatic Merkel cell carcinoma.

We report a cytogenetic study of six Merkel cell carcinomas (MCC) in which rearrangement of chromosome 1 was noted in four cases: two cases were trisomic, in one case there was a reciprocal translocation between chromosomes 1 and 5 [t(1;5)(p36;p13)], and in the fourth case all cells had a normal chromosome 1 and three derivatives, a del(1)(p22) and del(1)(q21), and a translocation involving material of unknown origin to the long arm, t(1;?)(q21;?). Four cases demonstrated loss of chromosome 13; in two of these, both copies were lost, and the survival for these two patients was much longer than is common for MCC patients. Partial trisomy of chromosome 11 was noted in two cases, and two patients demonstrated loss of chromosome 22 in all cells examined. Although no consistent chromosome change was noted in our cases, our data and those of previously published reports, show that abnormalities of chromosomes 1, 11, and 13 occur in 30-47% of cytogenetic reports of this rare malignancy.

Aged↗
PubMed1993

Prognostic markers in cancers of the head and neck region.

Increasing research initiatives in head and neck cancer over the past 5 years have resulted in the identification of several 'new' biologic parameters which may be of prognostic importance. This review discusses the limitations of traditional parameters and outlines several promising developments in the study of proliferation markers, molecular biology, immunobiology and flow cytometry as they relate to head and neck cancer.

Biomarkers, Tumor↗
PubMed1993

Chemosensitivity testing of primary cultures of Merkel cell cancer.

Twenty-seven tumor specimens from patients with Merkel cell carcinoma (MCC) were tested for chemosensitivity against a battery of nine cytotoxic drugs in a short-term antimetabolic assay measuring inhibition of thymidine incorporation. Dose-response curves were constructed by plotting drug concentration in micrograms/ml versus % control [3H]thymidine incorporation. Specimens were considered 'sensitive' to a drug if, at the approximate peak plasma concentration (PPC), the inhibition of [3H]thymidine was greater than 50% when compared with untreated control primary cultures. The assay revealed a 'sensitive' tumor in 19 of 20 specimens and 16 of 17 patients had a tumor that was 'sensitive' to at least one drug tested in the assay system. The highest sensitivity in order of frequency was found with doxorubicin, epirubicin, cyclophosphamide, etoposide and cisplatin. At least 40% of the tumors were 'sensitive' to these five drugs. Cyclophosphamide was chosen as the most active drug (at PPC) in 10 of 19 assays (53%), etoposide in seven of 17 (41%), doxorubicin in four of 19 (21%), chlorambucil in one of 12 (8%) and cisplatin in one of 18 (5%) of assays. Though our results are preliminary, we have identified for the first time a range of cytotoxic drugs which appear effective against MCC in vitro. Our main task now is to determine whether our in vitro predictive assay will correlate with clinical benefit to the patient.

Antineoplastic Agents↗