Bladder preservation by concurrent chemoradiation for muscle-invasive bladder cancer: Applicability in low-income countries

Background

Radical cystectomy is the standard treatment for patients with muscle-invasive urinary bladder cancer; however, is associated with major treatment – related morbidity. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. As such, several groups have explored effectiveness of less radical therapeutic strategies that aim at bladder preservation. Nonetheless, there is scarcity of reports assessing the applicability of urinary bladder-sparing outside developed countries.

Aim

Determine the achievable outcomes for patients with muscle-invasive urinary bladder cancer treated via bladder-sparing techniques in a low income country.

Materials and methods

Fourteen consecutive patients with a diagnosis of muscle-invasive urinary bladder cancer (clinical stage; T2-3N0M0) were treated via a bladder-sparing approach at King Hussein Cancer Center (Amman, Jordan) between 2005 and 2009. Records were electronically retrieved and retrospectively analyzed and included 11 males and 3 females from 41 to 74 years of age (median age, 61). Initial therapy consisted of trans-urethral resection of bladder tumor (TURBT) followed by induction chemotherapy then irradiation (4500cGy) with concurrent platinum-based chemotherapy. Urological evaluation directed additional therapy in a proportion of patients with irradiation (up to 6400 cGy) in patients who achieved CR.

Results

Eleven patients were evaluable for pathological response at time of re-staging; of whom 8 (73%) achieved CR and 3 (27%) achieved partial response (PR). In all but one patient; combined-modality treatment was well tolerated. After a median follow-up of 18.5 months (range, 3–48 months); 5 of 8 (62.5%) patients with CR were alive.

Conclusions

Bladder-sparing strategies via concurrent chemoradiation for muscle-invasive bladder cancer results in an acceptable rate of complete pathological response with adequate short-term outcomes. This approach appears applicable in low-income countries.     

Jordan Raff

Jordan Raff is a Cancer Research UK funded group leader at the Wellcome/CR-UK Gurdon Institute in Cambridge, England. He obtained his PhD from the Department of Biochemistry at Imperial College, London, and he worked as a Post-doctoral fellow at the Department of Biophysics and Biochemistry, University of California, San Francisco. He is currently a Director of the Company of Biologists, and on the committee of the British Society of Cell Biology. He has studied centrosomes and cell division in fruit flies throughout his scientific career.     

Epigenetic mechanisms in health and disease: BCEC 2017

The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Epigenetic Mechanisms in Health and Disease” was held in Barcelona, October 26-26, 2017. The 2017 BCEC was the fifth and last edition of a series of annual conferences organized as a joint effort of five leading Barcelona research institutes together with B-Debate. This edition was organized by Albert Jordan from the Molecular Biology Institute of Barcelona (IBMB-CSIC) and Marcus Bushbeck from the Josep Carreras Leukaemia Research Institute (IJC). Jordi Bernués, Marian Martínez-Balbás, and Ferran Azorín were also part of the scientific committee. In 22 talks and 51 posters, researchers presented their latest results in the fields of histone variants, epigenetic regulation, and chromatin 3D organization to an audience of around 250 participants from 16 countries. This year, a broad number of talks focused on the epigenetic causes and possible related treatments of complex diseases such as cancer. Participants at the 2017 BCEC elegantly closed the series, discussing progress made in the field of epigenetics and highlighting its role in human health and disease.     

Carlo M. Croce: Seeking Truth and Beauty

Believe it or not, as a boy Carlo Croce liked to hang out in art museums, to his mother’s chagrin. There are a lot of art museums in Italy, so his mother started dropping him off and going off to the coffee bar to find more interesting company. He bought his first painting, an old master, at age 12 and that used all his savings. He didn't resume his old master collection until he was in his 30s and had saved some money from his job at the Wistar Institute in Philadelphia. He now has an exciting and growing collection.In the meantime, he received his MD degree from the University of Rome “La Sapienza” while reading textbooks and journals in English to supplement the old style medical education. He planned to join Karl Habel at Scripps Clinic in 1970 for a research fellowship just as Dr. Habel was struck in his prime by a monkey B virus infection, so Carlo was diverted from California to Philadelphia to join Hilary Koprowski's internationally known Wistar Institute of Anatomy and Biology. I was a Ph.D. student at Wistar at the time and witnessed the arrival of the quiet 25 yr. old Italian who was too shy to try out his textbook English.He began his work in somatic cell genetics and virology in a large laboratory where a number of us worked on related projects, including Barbara Knowles (now Associate Director for Research at Jackson Laboratory) and Davor Solter (now Director of Developmental Biology, Max Planck Institute, Freiburg, Germany).One of his first accomplishments was to map the very first viral integration site on chromosome 7q in an SV40 transformed fibroblast cell line, using human-mouse somatic cell hybrids that retained human chromosome 7, the SV40 T-antigen and the SV40 genome. Very recently, one of his hybrid clones was used by others to clone the SV40 genome integration site and to show that the SV40 genome had integrated into a common fragile site.Still using somatic cell hybrids, Carlo Croce and his laboratory began in the late 70s and early 80s to map genes important in cancer, such as the immunoglobulin genes that are rearranged in lymphomas, along with the MYC and BCL2 genes among others. These experiments took advantage of the leukemia/lymphoma specific translocation to walk from immunoglobulin loci, and later TCR loci, into the oncogene loci juxtaposed by translocation, the beginning of positional cloning of translocation breakpoints. These studies involved collaborations with valued colleagues, including Peter Nowell, the co-discoverer with David Hungerford, of the Philadelphia chromosome, the first reported cancer specific chromosome alteration. In the exciting decode of the 1980s, the Croce laboratory published 23 reports in Science, including the discovery of the BCL2 gene with Yoshiide Tsujimoto (now University of Osaka). They also observed that mistakes by immunoglobulin family rearrangement/recombination machinery was responsible for the type of chromosome translocations that involved the IG and TCR genes.Carlo Croce has been not only an outstanding laboratory scientist with numerous important discoveries to his credit; he has also been the Director of an NCI designated Cancer Center, first at the Fels Institute for Cancer Research, where he built a first class basic cancer research faculty from the ground up. In 1991, he moved his cancer research faculty to Jefferson Medical College, where it took the name of its benefactor, Sidney Kimmel, and became the Kimmel Cancer Center. At KCI the Croce laboratory continued to find and study genes involved in cancer development: oncogenes activated by translocation such as ALL1, involved in biphenotypic leukemias, discovered with another important collaborator, Eli Canaani and TCL1 (with Gianni Russo’s lab) activated by translocation to the TCRa locus in lymphomas of ataxia telangiectasia patients; or tumor suppressor genes, lost usually through deletions in epithelial cancers, such as FEZ1/LZTS1 at 8p22 lost in prostate, breast and other cancers and the FHIT gene at the 3p14.2 common fragile site (discovered in a collaboration with my laboratory), confirming a long held hypothesis that genes at chromosome fragile sites could contribute to cancer development through frequent chromosomal rearrangements. At the same time, Carlo Croce was living the nearly always tumultuous life of a Director of a Cancer Center, involving recruitment of faculty, constant bargaining with Deans, department chairman, University administrators, but he still manages to fit in a few skiing meetings, gossip sessions with colleagues like Web Cavenee, visits for good coffee, good food and TV appearances in his beloved Italy and most of all, he still manages to study, examine, buy, transport, restore, reframe and admire his old master paintings. I think he loves it as much as science because discovering a beautiful but misattributed painting at an obscure or even well known auction house, buying it and then proving that it is actually a painting by a Gentileschi or a Cavallino is as thrilling and elegant as discovering the connection between a specific gene alteration and its cancer.     

Four decades of discovery in breast cancer research and treatment--an interview with V. Craig Jordan. Interview by Marc Poirot

V. Craig Jordan is a pioneer in the molecular pharmacology and therapeutics of breast cancer. As a teenager, he wanted to develop drugs to treat cancer, but at the time in the 1960s, this was unfashionable. Nevertheless, he saw an opportunity and through his mentors, trained himself to re-invent a failed "morning-after pill" to become tamoxifen, the gold standard for the treatment and prevention of breast cancer. It is estimated that at least a million women worldwide are alive today because of the clinical application of Jordan's laboratory research. Throughout his career, he has always looked at "the good, the bad and the ugly" of tamoxifen. He was the first to raise concerns about the possibility of tamoxifen increasing endometrial cancer. He described selective estrogen receptor modulation (SERM) and he was the first to describe both the bone protective effects and the breast chemopreventive effects of raloxifene. Raloxifene did not increase endometrial cancer and is now used to prevent breast cancer and osteoporosis.The scientific strategy he introduced of using long term therapy for treatment and prevention caused him to study acquired drug resistance to SERMs. He made the paradoxical discovery that physiological estrogen can be used to treat and to prevent breast cancer once exhaustive anti-hormone resistance develops. His philosophy for his four decades of discovery has been to use the conversation between the laboratory and the clinic to improve women's health.     

Thermotolerant strain of Bacillus licheniformis producing lipase

A thermotolerant variant of Bacillus licheniformis strain H1 (isolated from Jordan valley soil), was highly active in degrading macromolecules, and possessed a lipase activity with a half life of 30 min at 70°C. This activity was produced during exponential growth. The extracellular crude lipase showed maximal activity at pH 10, and retained 65% of its stability at pH 12.The author is with the Department of Biological Sciences, University of Jordan, P.O. Box 2686, Amman 11181, Jordan     

Geographic Aspects of Malignant Disease

In view of recent publications describing a malignant lymphoma in African children, a review is presented of the geographical distribution of various cancers throughout the world. The epidemiological studies which have revealed these malignant tumours have provided valuable clues to the control of cancer and represent an effort to reduce and ultimately to eliminate certain forms of malignant disease. In Canada the distribution of cancer of the stomach has been observed to vary among provinces, being higher in Newfoundland than elsewhere. A study to determine the validity of this observation is currently being undertaken by the National Cancer Institute of Canada.     

Distribution of transferrin C subtypes among the Bedouin and non-Bedouin populations of Jordan

The distribution of transferrin C subtypes was studied in the population of Jordan. The sample comprised 121 Bedouins and 382 other Jordanians from Amman. The frequency of TfC2 was found to be 0.26 among the Bedouins and 0.23 among the non-Bedouin population. TfD was present in low frequency (0.005) among both the Bedouin and non-Bedouin populations.     

The Distribution of Heavy Metals in Urban Street Dusts of Karak City,Jordan

Street dust samples from urban and suburban areas were collected from the city of Karak, Jordan, during the summer season of 2004. Samples were analyzed for their heavy metal concentrations (Pb, Cu, Zn, Ni, Fe, Cr, Cd, and Mn). The results showed that all heavy metals are higher in city urban areas than the surrounding suburbs. The distribution and concentrations of heavy metals in all areas show automobile originated sources such as emissions and wear and tear of automobiles were the main source of pollution. Despite the fact that the city of Karak and the capital Amman are under the same climatic conditions and same type of fuel used in both cities, the heavy metal concentrations of street dust samples were lower in Karak than Amman due to the lower traffic density.     

In vitro cultivation of human renal cell cancer

Summary A technique for initiating and propagating epithelial cell cultures of human renal cell cancer and adjacent nontumor kidney is described. Seventy-five percent of the tumors and 79% of the adjacent kidney specimens cultured with this method have shown initial outgrowth and have been subcultured at least once. Two renal cell cancer cultures initiated by this method have now been in continuous culture more than 6 months, have been subcultured 27 and 19 times, and now appear to be stable lines. The ability to establish long-term in vitro cultures of human renal cell cancers will facilitate studies concerning the immunoreactivity, cholesterol metabolism, the isolation of renal-cell-cancer-specific antigens, and in vitro chemotherapy testing and will further our understanding of the basic biology of human renal cell cancer. American Cancer Society Clinical Fellow 1975–1976. Supported in part by Grants CA 13095-03 and CA 15551-03 from the National Cancer Institute.     

Rays of Hope from the Ecological Restoration Alliance of Botanic Gardens,following its recent meeting in Amman,Jordan

In the spring of 2015, the Ecological Restoration Alliance (ERA) of Botanic Gardens held its fourth international meeting in Amman, Jordan, hosted by the Royal Botanic Garden of Jordan. Three regional working groups were launched, for the Middle East, East Africa, and Latin America, and new partnerships were forged to support ecological restoration initiatives led by botanic gardens in Jordan, Oman, and elsewhere. A one‐day public symposium, attended by over 100 people, was also held—the most significant public meeting on ecological restoration held to date in the Middle East. A communications strategy for regional outreach was agreed upon starting with the translation of several Society for Ecological Restoration (SER) foundation documents into Arabic. A peer‐reviewed translation of the SER International Primer on Ecological Restoration has already been produced by staff of the Royal Botanic Garden of Jordan and posted on the SER website. Further efforts will be made to promote public awareness in Jordan and regionally, in support of existing conservation and restoration programs, and to promote greater integration of ecological restoration programs in national and regional development schemes and government policies. Key action points were agreed upon to promote the practice of ecological restoration and the role of botanic gardens globally vis‐à‐vis policy makers and funders.     

Whole-genome sequencing and phylogenetic analysis of rabies viruses from Jordan

Human fatalities caused by rabies are rarely reported in Jordan; however, domestic animals are more likely to fall victim to rabies compared to wild animals, at least this is the case in Jordan due to the presence of canine rabies. In this study, twelve brain samples from domestic and wild animals suspected of being infected with rabies virus from different regions of Jordan were collected during 2019. Seven of them tested positive using the fluorescent antibody test and real-time SYBR RT-PCR assay. Five specimens were from stray dogs and two from foxes. The whole genome sequences were obtained from the positive samples. Sequence analysis showed that one dog virus from Al Quwaysimah city located in Amman governorate, was closely related to an Israeli strain belonging to a Cosmopolitan ME1a clade. The genomes of the remaining six viruses (four from dogs and two from foxes) collected from different areas of Jordan were genetically-related to each other and clustered together with sequences from Iran and Turkey; all belong to Cosmopolitan ME2 clade. These sequences were analyzed with six other Jordanian rabies virus nucleoprotein (N) gene sequences available in the public database, five of them belong to ME1a clade and one belongs to ME1b clade. Rabies virus whole genome data is scarce across the Middle East. This study provides a better understanding of the molecular epidemiology of rabies virus in the region.     

Induction of hyperplasia and anaplasia by carcinogens in organ cultures of mouse prostate

Summary In an effort to establish a test system to examine the carcinogenic potential of chemicals, mouse prostate explants were maintained as organ cultures and the effects of carcinogenic and noncarcinogenic compounds were examined at various intervals after treatment. The degree of hyperplasia produced by a compound was determined by the colcemid metaphase arrest technique. Extensive hyperplasia of the prostatic epithelium occurred at 8 days after treatment with 3-methylcholanthrene, the 11–12 epoxide of methylcholanthrene, benzo(a)pyrene and N-methyl-N-nitro-N-nitrosoguanidine. At 12 days most carcinogentreated explants were anaplastic. The noncarcinogenic compounds, pyrene and phenanthrene, did not produce a mitotic stimulatory effect on the epithelium of the explants. The data suggest that the organ culture system of mouse prostate may be employed as a test system to obtain preliminary information regarding the carcinogenicity of a compound. This investigation was supported by Contract No. NO1-CP-22064 from the Lung Cancer Segment, Division of Cancer Cause and Prevention, National Cancer Institute, NIH, Department of Health, Education and Welfare.     

Role of oncoproteomics in the personalized management of cancer

Oncoproteomics is the term used to describe the application of proteomic technologies in oncology and parallels the related field of oncogenomics. It is now contributing to the development of personalized management of cancer. Proteomic technologies are used for the identification of biomarkers in cancer, which will facilitate the integration of diagnosis and therapy of cancer. Molecular diagnostics, laser capture microdissection and protein biochips are among the technologies that are having an important impact on oncoproteomics. The discovery of protein patterns developed by the US Food and Drug Administration/National Cancer Institute Clinical Proteomics Program is capable of distinguishing cancer and disease-free states with high sensitivity and specificity and will also facilitate the development of personalized therapy of cancer. Examples of application are given for breast and prostate cancer and a selection of companies and their collaborations that are developing application of proteomics to personalized treatment of cancer are discussed. Continued refinement of techniques and methods to determine the abundance and status of proteins in vivo holds great promise for the future study of normal cells and the pathology of associated neoplasms. Personalized cancer therapy is expected to be in the clinic by the end of the first decade of the 21st century.     

Highlights of recent developments and trends in cancer nanotechnology research—View from NCI Alliance for Nanotechnology in Cancer

Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood.     

癌症痛的神经生物学机制研究进展

癌症痛是影响癌症病人生活质量的一个严重问题 ,但长期以来由于缺乏合适的动物模型 ,对其神经机制的研究甚少。近年出现的小鼠股骨、跟骨、肱骨和大鼠胫骨癌症痛模型 ,极大地推动了癌症痛的基础研究。初步研究表明 ,癌症痛有其独特的神经化学机制 ,骨质破坏、外周敏化、中枢敏化及神经侵蚀都参与了癌症痛的产生。本文综述了癌症痛动物模型、癌症痛的产生机制及其药物治疗等方面的研究进展。     

The cytotoxicity of protoneodioscin (NSC-698789), a furostanol saponin from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro

Protoneodioscin (NSC-698789) is a furostanol saponin isolated from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for cancer treatment. Our studies showed that protoneodioscin is cytotoxic against most cell lines from leukemia and solid tumors in the NCI's (National Cancer Institute, USA) anticancer drug screen. Leukemia, CNS cancer, and prostate cancer are the most sensitive subpanels to protoneodioscin, while melanoma, ovarian cancer, and renal cancer are less sensitive. The preliminary animal studies showed that the maximum tolerant dose of protoneodioscin was 600 mg/kg to mice. Based on an analysis of the COMPARE software with protoneodioscin as a seed compound, no compounds in the NCI's database have similar cytotoxicity patterns to those of protoneodioscin, indicating a potentially novel mechanism of anticancer action involved.     

Emerging roles for cancer registries in cancer control

Cancer registries are a vital part of the national cancer effort to cut United States cancer mortality rates in half by the year 2000. Registries provide the data to focus programs and monitor progress. Success in meeting the year 2000 goal will require aggressive attention to the opportunities for prevention, early detection, treatment, and applied cancer control research, all of which complement the current emphasis on basic research.     

Synthesis and in vitro antineoplastic evaluation of certain 16-(4-substituted benzylidene) derivatives of androst-5-ene

In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antiproliferative activity against cancer cells, we synthesized certain 16-[4-(NO2, CN, and i-Pr)substituted]benzylidene derivatives of androst-5-ene, 7-25, with pyrrolidino functionality in the 3beta-position of the steroid nucleus, i.e., 13-18 and 25. The selected compounds were examined for their cytotoxicity against a panel of three human cancer cell lines at the National Cancer Institute (NCI), Bethesda, USA. The results presented herein provide experimental evidence that compounds 7, 9, 10, 12, 16, and 19-21 induced apoptosis in human cancer cells.