Direct Evidence on the Immune-Mediated Spontaneous Regression of Human Cancer: An Incentive for Pharmaceutical Companies to Develop a Novel Anti-Cancer Vaccine

Ai Scientific Awarded R&D Start Grant. CSIRO Drug Effective against Bird Flu. AustCancer Commences Anti-cancer Vaccine Phase II Trial. New Approach against Cancer. Non-invasive Cancer Test. China’s Chemical Pharmaceutical Sector Q1 2003 Performance. International Generic Companies Target India’s Manufacture Infrastructure. Cardinal Health Sets up Regional Office in Singapore. BRV Enters Agreement with Genedata.

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Vigorous Premalignancy-specific Effector T Cell Response in the Bone Marrow of Patients with Monoclonal Gammopathy

Journal of Experimental Medicine ◽

10.1084/jem.20031030 ◽

2003 ◽

Vol 198 (11) ◽

pp. 1753-1757 ◽

Cited By ~ 131

Author(s):

Madhav V. Dhodapkar ◽

Joseph Krasovsky ◽

Keren Osman ◽

Matthew D. Geller

Keyword(s):

T Cells ◽

Immune System ◽

T Cell ◽

Cell Response ◽

Direct Evidence ◽

Human Cancer ◽

T Cell Response ◽

Immune Recognition ◽

Effector T Cell ◽

Specific Effector

Most approaches targeting the immune system against tumors have focused on patients with established tumors. However, whether the immune system can recognize preneoplastic stages of human cancer is not known. Here we show that patients with preneoplastic gammopathy mount a vigorous T cell response to autologous premalignant cells. This preneoplasia-specific CD4+ and CD8+ T cell response is detected in freshly isolated T cells from the BM. T cells from myeloma marrow lack this tumor-specific rapid effector function. These data provide direct evidence for tumor specific immune recognition in human preneoplasia and suggest a possible role for the immune system in influencing the early growth of transformed cells, long before the development of clinical cancer.

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Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies

Cancers ◽

10.3390/cancers12113327 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3327

Author(s):

Tabitha G. Cunliffe ◽

Emily A. Bates ◽

Alan L. Parker

Keyword(s):

Viral Genome ◽

Recent Progress ◽

Oncolytic Viruses ◽

Transformed Cells ◽

Immunogenic Cell Death ◽

Full Potential ◽

Immune Mediated ◽

Efficacious Treatment ◽

Anti Cancer ◽

Improvement In Survival

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, although immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus, have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergise with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.

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Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment

Chemical Science ◽

10.1039/c9sc06334j ◽

2020 ◽

Vol 11 (15) ◽

pp. 3996-4006 ◽

Cited By ~ 3

Author(s):

Iris A. Bermejo ◽

Claudio D. Navo ◽

Jorge Castro-López ◽

Ana Guerreiro ◽

Ester Jiménez-Moreno ◽

...

Keyword(s):

Conformational Analysis ◽

Cancer Vaccine ◽

In Vivo Assays ◽

Anti Cancer

An anti-cancer vaccine based on an unnatural antigen with an sp2-iminosugar fragment.

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The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181115112236 ◽

2019 ◽

Vol 17 (1) ◽

pp. 57-67

Author(s):

Yepeng Luan ◽

Jinyi Liu ◽

Jianjun Gao ◽

Jinhua Wang

Keyword(s):

Cell Lines ◽

High Efficiency ◽

Human Cancer ◽

Human Tumor ◽

Cytotoxic Agents ◽

Cancer Drug ◽

Human Cancer Cell Lines ◽

Incidence And Mortality ◽

Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

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Characterization of the anti-cancer-cell parasporal proteins of aBacillus thuringiensisisolate

Canadian Journal of Microbiology ◽

10.1139/w00-084 ◽

2000 ◽

Vol 46 (10) ◽

pp. 913-919 ◽

Cited By ~ 17

Author(s):

Satoko Yamashita ◽

Tetsuyuki Akao ◽

Eiichi Mizuki ◽

Hiroyuki Saitoh ◽

Kazuhiko Higuchi ◽

...

Keyword(s):

Bacillus Thuringiensis ◽

Cancer Cell ◽

Human Cancer ◽

Proteolytic Processing ◽

Proteinase K ◽

Major Protein ◽

Human Cancer Cell ◽

Soil Isolate ◽

Anti Cancer

An unusual activity, associated with non-insecticidal and non-haemolytic parasporal inclusion proteins of a Bacillus thuringiensis soil isolate, designated 89-T-26-17, was characterized. The parasporal inclusion of this isolate was bipyramidal, rounded at both ends, containing proteins of 180, 150, 120, 100, and 88 kDa. No homologies with the Cry and Cyt proteins of B. thuringiensis were detected based on N-terminal sequences. Proteolytic processing of the inclusion proteins by proteinase K, trypsin, and chymotrypsin produced a major protein of 64 kDa exhibiting cytocidal activity against human leukaemic T cells and uterus cervix cancer (HeLa) cells. The protease-activated proteins showed no cytotoxicity to normal T cells.Key words: Bacillus thuringiensis parasporal inclusion, non-insecticidal, non-haemolytic, cytocidal activity, human cancer cell.

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New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells

Antioxidants ◽

10.3390/antiox9111077 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1077

Author(s):

Gabriele Carullo ◽

Sarah Mazzotta ◽

Adrian Koch ◽

Kristin M. Hartmann ◽

Oliver Friedrich ◽

...

Keyword(s):

Healthy Lifestyle ◽

Apoptotic Cell ◽

Human Cancer ◽

Natural Antioxidants ◽

In Vitro Assays ◽

Human Cancer Cell Lines ◽

Cancer Management ◽

Anti Cancer ◽

Colorectal Cancer Cells

Nowadays, the beneficial role of a healthy lifestyle, particularly emphasizing the quality of foods and cancer management, is accepted worldwide. Polyphenols and oleic acid play a key role in this context, but are still scarcely used as anti-cancer agents due to their bio-accessibility limits. Therefore, we aimed to synthesize a set of new oleoyl-hybrids of quercetin, morin, pinocembrin, and catechin to overcome the low bioavailability of polyphenols, throughout a bio-catalytic approach using pancreatic porcine lipase as a catalyst. The in vitro assays, using a wide panel of human cancer cell lines showed, mainly for two novel regioisomer oleoyl-hybrids of quercetin, a remarkable increase in apoptotic cell populations. We suggested that the DNA damage shown as ɣH2AX signals might be the major cause of apoptotic cell death. Finally, we demonstrated convincing data about two novel polyphenol-based hybrids displaying a highly selective anti-cancer cytotoxicity and being superior compared to their reference/parental compounds.

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A Comprehensive Study on Availability of Anti-cancer drugs in Dhaka City, Bangladesh

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v23i2.48336 ◽

2020 ◽

Vol 23 (2) ◽

pp. 155-166

Author(s):

Rumman Reza ◽

Md Nazmus Samdani ◽

Niaz Morshed ◽

Nusrat Ahmed

Keyword(s):

Cancer Care ◽

Negative Relationship ◽

Pharmaceutical Journal ◽

Expert Advice ◽

Pharmaceutical Companies ◽

Dhaka City ◽

Cancer Drugs ◽

College Hospital ◽

Medical College ◽

Anti Cancer

With the increasing rate of people being affected by cancer in Bangladesh, the disease has become a national concern. Anti-cancer drugs play a significant and crucial role in cancer treatment regimen. Inadequate access to essential anti-cancer medicines may impose serious public health problems in Bangladesh. The present study gives an insight on the availability of eleven WHO enlisted essential anticancer drugs that are commonly prescribed for the top five prevalent cancer types (Breast, Oesophagus, Lung, Cervix, Lips and Oral cavity) in Bangladesh. Expert advice on which essential anti-cancer medicines are commonly prescribed were gathered from oncologists of three medical college hospitals (Dhaka Medical College Hospital (DMCH), Bangabandhu Sheikh Mujib Medical University (BSMMU) and National Institute of Cancer Research and Hospital (NICRH). The study was conducted among a total of 151 pharmaceutical drug stores including 119 retail, 27 model and 5 hospital pharmacies. The sample size of 151 pharmacies was calculated for 4547 pharmacies in Dhaka district with 95% confidence interval and 8% margin of error. It was found that 74% of the pharmacy stores surveyed kept no anti-cancer drugs at all. There is a significant negative relationship between price and availability of oncology medicine for which Pearson’s correlation co-efficient ‘r’ is found to be -0.739 (p=0.01). This means that high priced medicines are less available. Pharmacy stores keep anti-cancer drugs from both local (81.9%) and foreign (18.1%) pharmaceutical companies. In order to evaluate sales performance of pharmacies in context of oncology drugs, monthly number of cancer patients buying medicines from these pharmacies has been studied as well. It has been found that supply of anti-cancer drugs by pharmaceutical companies among medicine stores is not homogenous. Availability and sales rate of oncology products in some pharmacies situated within the same area is way more than others and the number of customer (cancer patient) varies by wide margins. A comparative analysis on availability rate of model versus retail pharmacies in different areas of Dhaka city has been carried out. Retail pharmacies near cancer-care hospitals tend to keep more anti-cancer medicines compared to those situated away from cancer-care hospitals. Bangladesh Pharmaceutical Journal 23(2): 155-166, 2020

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