CD34: to select or not to select? That is the question.

Recent evidence suggests that expression of CD34 on the cell membrane does not always correlate with stem cell activity. In the mouse, there is a highly quiescent population of stem cells that lacks CD34 expression, but has full reconstituting capacity. The current review addresses the discovery of a similar population of dormant CD34-negative human hematopoietic stem cells. This information casts some uncertainty on the benefits of CD34+ cell isolation for stem cell transplantation, until more is known about the novel CD34-negative stem cell population. Methods designed to achieve removal of specific mature blood cell lineages might prove to be most advantageous in the future.     

Resveratrol--from the bottle to the bedside?

Resveratrol, a naturally occurring plant antibiotic has been the focus of a number of studies investigating its biological attributes, which include anti-oxidant activity, anti-platelet aggregation effect, anti-atherogenic property, estrogen-like growth promoting effect, growth inhibiting activity, immunomodulation, and chemoprevention. More recently, since the first report on the apoptosis inducing activity of resveratrol in human cancer cells, the interest in this molecule as a potential chemotherapy agent has significantly intensified. Not only has its role as an anti-cancer agent been corroborated, but the precise mechanism(s) of the anti-cancer activity of resveratrol is/are being elucidated. Our group has been active in studying the cross talk between the caspase family of proteases and mitochondria, in drug-induced apoptosis. In this regard, we have shown that the cancer preventive activity of resveratrol could be attributed to its ability to trigger apoptosis in human leukemia and breast carcinoma cells. The cytotoxicity of resveratrol is restricted against these transformed cell types due to its ability to selectively upregulate CD95-CD95L interaction on the tumor cell surface, unlike normal peripheral blood cells. Despite the involvement of the CD95 signaling pathway, apoptosis induced by resveratrol is not accompanied by robust caspase 8 activation, but involves mitochondrial release of cytochrome C and downstream activation of caspases 9 and 3. We also extrapolate these in vitro findings in a murine model of carcinogensis, and demonstrate in vivo induction of apoptosis in mouse skin papillomas. These findings highlight the chemotherapeutic potential of this polyphenolic compound.     

Laudation to Professor Dr.Dr.h.c. Qiu Fazu—Greetings to his 90th Birthday

The story goes back to the early time of 1945, a verycold winter in Germany. The temperature of Munich andits vicinities dropped to 20 degree of frost and it was snow-ing heavily. German army was su?ering defeat on botheastern and western fronts. The bombers of the AlliedArmy bombed almost all German cities and towns, with80% of the cities being destroyed. American army wouldsoon liberate the Dachau, a city near Munich. SS-troops,with jail prisoners under their escort, retreated to BadT¨…     

Primary non-Hodgkin lymphoma of the breast. Is it possible to avoid mastectomy?

Primary lymphoma of the breast is a rare disease that has been estimated to represent from 0.05% to 0.53% of all malignant breast tumors and approximately 2.2% of all extranodal lymphomas. The aim of this study is to review all cases of primary lymphoma of the breast at the Institute of Oncology and Radiology of Serbia from 1984 to 1996 in order to determine the incidence, patterns of clinical presentation, radiological features, histopathology, mode of therapy and outcome of the disease. The criteria for inclusion in this retrospective study corresponded to a revision of the original criteria suggested by Wiseman and Liao. The clinical histories of ten patients with breast lymphomas were reviewed. Clinical follow-up was obtained through a review of the patients hospital chart or by direct contact with the patients. Ten cases of primary lymphoma of the breast have been identified during the 12-yr period, presenting 0.05% of all patients with malignant breast disease. All patients were female, median age at diagnosis 58 years (range 49-69), all presented with breast lumps (3 right, 7 left) of median size 5 cm (range 3.5-8 cm). Mammography and breast echography were unable to bring a suspicion of lymphoma. Histologically, 6 cases were diffuse large cell, 3 of which with features consistent with immunoblastic lymphoma; 2 were diffuse mixed cells and 2 had small lymphocytic morphology. In 4 out of 5 patients, in the clinical stage corresponding to the "operable breast cancer" category, the ex tempore histological analysis could not differentiate lymphoma from cancer, so that all of them had mastectomy with axillary dissection. Those corresponding to the "locally advanced breast cancer" category, escaped mastectomy and a classical biopsy was performed, anticipating eventual neoadjuvant procedures. Thus, four patients underwent radical mastectomy, 1 wide local excision and 5 diagnostic biopsies. Further treatment included chemotherapy for 8 patients. The projected probability of a 10-years survival was 0,60. The rarity of this disease, and uneven treatment modalities make prognosis of breast lymphoma difficult. It seems that cooperation between the surgeon and the pathologist is necessary in order to reach the correct diagnosis during ex tempore analysis. With the limitations of available diagnostic procedures, it appears that most patients with breast lymphoma, in the stage corresponding to the "operable breast cancer" category, will unnecessarily undergo mastectomy and axillary dissection as primary treatment approach.     

Preface to the Inaugural Issue

This is the first issue of the English edition for the Chinese Jotn‘nal of Clinical Oncology, an official journal of the Chinese Anti-Cancer Association (CACA). As the editor-in-chief, I would like to express my appreciation to all the editors and editorial staff who have made tremendous effort in giving birth to this new journal. I would also     

Laudation to Professor Dr.Dr.h.c.Qiu Fazu Greetings to his 90~(th) Birthday

The story goes back to the early time of 1945,a verycold winter in Germany.The temperature of Munich andits vicinities dropped to 20 degree of frost and it was snow-ing heavily.German army was suffering defeat on botheastern and western fronts.The bombers of the AlliedArmy bombed almost all German cities and towns,with80% of the cities being destroyed.American army wouldsoon liberate the Dachau,a city near Munich.SS-troops,     

To PET or not to PET? That is the question. Staging in anal cancer

BackgroundAnal cancer is a rare tumour accounting for ∼2% of all colorectal cancers between 1997 and 2000 in the UK. Staging is still dominated by DRE (digital rectal examination), computed tomography (CT) and magnetic resonance imaging (MRI) imaging. The role of PET as a definitive modality is still emerging and there are relatively few adequate studies in the literature.MethodsWe looked at patients treated radically for anal cancer at Mount Vernon Cancer Centre (UK) between 2009 and 2010. Eighty-eight patients underwent treatment according to data-based coding records of which 46 had positron emission tomography (PET)/CT scans. Notes were unavailable for three patients. We compared staging following conventional modalities (DRE, MRI and CT) and PET/CT scans for these 43 patients.ResultsIn 18 patients, the PET/CT stage differed from MRI. PET/CT altered the stage in 42% of patients but changes in subsequent management were not implemented.ConclusionsOur data show that PET/CT does alter staging in a significant number of cases although it did not lead to change in management under the current guidelines. Furthermore, there is agreement that PET/CT shows greater sensitivity for detection of lymph nodes and our study has demonstrated a distinct trend towards upstaging of anal cancer with PET/CT.     

Evaluating the drug-target relationship between thymidylate synthase expression and tumor response to 5-fluorouracil. Is it time to move forward?

Thymidylate synthase is a target of 5-fluoruracil, a pyrimidine analog used to treat gastrointestinal and other cancers. The 5-fluorouracil metabolite, fluoro-deoxyuridine monophosphate, forms a ternary complex with thymidylate synthase and 5,10-methylene tetrahydrofolate. The purpose of this study was to evaluate the time-honored connection between thymidylate synthase and 5-fluorouracil. From our literature search spanning reports from 1995 to 2007 published in journals having an impact factor greater than 2, we stratified the tumors within each article, according to low versus high thymidylate synthase expression. These groups were subdivided into responders, stable disease or disease progression. The relationship between thymidylate synthase expression and 5-fluorouracil response was analyzed for the overall group, as well as for subsets. Overall, the literature supported an approximately 2-fold inverse relationship between thymidylate synthase expression and response to 5-fluoruracil. We found no change in the trend for a relationship between thymidylate synthase and 5-fluorouracil when the literature was stratified by date of publication, impact factor of the journal in which the report was published, or substrate (mRNA versus protein) for measuring thymidylate synthase expression. Of note, there is no significant change in the trend when comparing 5-fluorouracil treatment alone or in combination with leucovorin. We found a decline of this trend when certain chemotherapeutics were used in combination with 5-fluorouracil. In sum, the connection between thymidylate synthase expression and patient response to 5-fluorouracil does not satisfy expectations for an effective drug-target relationship; and thus, studies of the thymidylate synthase tandem repeat status might only be clinically valuable in regards to patient toxicity. Thus, we question the reliability of thymidylate synthase expression as a clinical predictor of 5-fluorouracil response. Future research could perhaps be directed towards alternate targets and metabolites of 5-fluorouracil, in an effort to find a clinically relevant biomarker panel for response and to optimize fluoropyrimidine-based therapy.     

How to manage the menopause following therapy for breast cancer. is raloxifene a safe alternative?

Raloxifene is a selective oestrogen receptor modulator (SERM) that has anti-oestrogenic effects on breast and endometrial tissue and oestrogenic actions on bone, lipid metabolism and blood clotting. In postmenopausal women raloxifene decreases bone turnover and increases bone mineral density, reducing the incidence of vertebral fractures. Unlike tamoxifen, raloxifene does not cause endometrial hyperplasia or cancer, as demonstrated by endometrial monitoring with ultrasonography and biopsy during treatment. Evidence suggests that raloxifene lowers total low-density lipoprotein cholesterol levels behaving like oestrogens, but does not increase high-density lipoprotein cholesterol levels. In randomised clinical trials on postmenopausal women with osteoporosis, raloxifene reduced the risk of newly diagnosed ER-positive invasive breast cancer by 76% during a median of 40 months of treatment. However, raloxifene does not alleviate early menopausal symptoms, such as hot flushes and urogenital atrophy, and may even exacerbate some of them. In conclusion, raloxifene may be an alternative for the prevention of long-term effects of oestrogen deficiency (osteoporosis and heart diseases) in women with previous breast cancer not having hot flushes. For symptomatic patients, the association of raloxifene with different drugs which have demonstrated efficacy in the control of vasomotor symptoms is now under evaluation.     

Thyroid cancer in children and young adults in the North of England. Is increasing incidence related to the Chernobyl accident?

Population-based data on thyroid carcinomas was obtained from the Northern Region Young Person's Malignant Disease Registry to analyse the incidence of thyroid cancers in young people (<25 years) in the North of England for the period 1968 and 1997 and to assess if changes in incidence were consistent with the spatial and temporal distribution of the fallout from the Chernobyl nuclear accident. We compared incidence rates for differentiated (papillary or follicular) thyroid carcinomas 1968-1986 with those for 1987-1997. There were 75 cases of thyroid carcinoma diagnosed over the study period, of which 63 were differentiated carcinoma and 12 were medullary carcinoma. There were 26 young adults (15-24 years) diagnosed with differentiated thyroid carcinoma in the 19-year period 1968-1986 and 30 in the subsequent 11 years 1987-1997, Age standardised rate (ASR) 3.0 versus 6.5, respectively (rate ratio 2.2, 95% confidence interval (CI): 1.3-3.6). There were three children (aged <15 years) diagnosed with differentiated carcinoma in the period 1968-1986 and four in the period 1987-1997, ASR 0.2 versus 0.6 (rate ratio 2.7, 95% CI: 0.6-12.1). Regression models showed a significant increase in the incidence of thyroid cancer after the Chernobyl accident (P=0.002). In Cumbria, the area receiving the heaviest fallout in the UK, the increase in incidence was much greater (rate ratio 12.19, 95% CI 1.5-101.2). These temporal and spatial changes in incidence are consistent with a causal association with the Chernobyl accident although a greater effect in the younger rather than the older age group would have been anticipated. However, factors including improvements in ascertainment and earlier detection of tumours may also have contributed to the increasing incidence. Further collaborative international studies are needed to investigate changes in the incidence of thyroid cancer in children and young adults.     

Can the stroma provide the clue to the cellular basis for mammographic density?

Mammographic density is recognised as a useful phenotypic biomarker of breast cancer risk. Deeper understanding is needed of the cellular basis, but evidence is limited because of difficulty in designing studies to validate hypotheses. The ductal epithelial components do not adequately explain the physical and dynamic features observed. The stroma is thought to interact with ductal structures in cancer initiation. Stromal tissues might account for the mammographic features, and this interplay can be hypothesised to relate risk to density. In a paper in this issue of Breast Cancer Research, Alowami has shown a relationship between density and stromal proteins, which might provide useful insight into mammographic density.