ஜர்னல் ஆஃப் ஆன்காலஜி மொழிபெயர்ப்பு ஆராய்ச்சி

Metformin is the most widely administered anti-diabetic agent worldwide. In patients receiving metformin for metabolic syndrome or diabetes, it reduces the incidence and improves the survival of breast cancer (BC) patients. We have previously shown that metformin is particularly potent against triple negative breast cancer (TNBC), with a reduction of proliferation, oncogenicity and motility, inhibition of pro-oncogenic signaling pathways and induction of apoptosis. These BCs are well recognized to be highly dependent on glucose/glucosamine (metabolized through anaerobic glycolysis) and lipids, which are metabolized for the production of energy and cellular building blocks to sustain a high rate of proliferation. We have previously demonstrated that metformin inhibits lipid metabolism, specifically targeting fatty acid synthase (FASN), cholesterol biosynthesis and GM1 lipid rafts in TNBC. We also reported that glucose promotes phenotypic aggression and reduces metformin efficacy. We now show that metformin inhibits several key enzymes requisite to glucose metabolism in TNBC, providing additional insight into why metformin is especially toxic to this subtype of BC. Our data suggests that the use of metformin to target key metabolic defects in lipid and carbohydrate metabolism in cancer may be broadly applicable, especially against highly aggressive malignant cells.

Background: The commonly encountered hazards in a healthcare setup include biological (infectious) hazards, chemical hazards, physical hazards, environmental hazards, and psychological hazards. The aim of this study was to conduct a survey of work related occupational hazards amongst the full time staff from various work areas and to assess the awareness, perceptions and levels of compliance to universal precautions and bio-safety measures.
Methods: A pre-structured questionnaire was developed based on literature survey and was distributed amongst staff from various work areas of the hospital viz. diagnostic laboratories, department of transfusion medicine and nursing department. Scales were based on standard methods.
Results: Responses were obtained from 66 participants (18 men, 48 women). Most respondents were nurses (57.57%) and technologists (28.79%). Common injuries encountered were musculoskeletal (62.12%), sharps (12.12%) and allergies (36.36%). Compliance to safe work practices including personal protective equipment and waste disposal ranged from 92-98%. Employee perceptions and awareness with respect to safety measures were generally ≥ 90%.
Conclusion: The survey showed that healthcare staffs were generally well aware of occupational hazards and biosafety issues. The general level of compliance to safety measures was high.

PARP1 is identified as an enzyme for addition of poly (ADP-ribose) to target protein(s) and is also important for DNA repair at the site of DNA single strand break (SSB). However, under PARP-inactivated states, unrepaired SSB is converted to double strand break (DSB) in S-phase, and then homologous recombination (HR) system participates in repair of DSB-injured DNA. In this process, BRCA1/2 and their binding effectors, such as RAD51 and PALB1, are recruited to the injured site for initiating HR-based DNA repair. If HR-associated molecules, such as BRCA1/2, are deficient via a dysfunctional mutation or down-regulated (so called, BRCAness), cancer cells undergo further DSBs and eventually result in apoptotic cell death. In response to HR-deficiency, PARP1 is activated to repress SSB, a source of DSB before DNA replication, hence suggesting a new target of PARP1 for inducing synthetic lethality under BRCAness. Indeed, PARP1 inhibitor (PARPi) is found to be useful for delaying the progression of BRCA1/2-mutated ovarian cancers in phase-II clinical trials. Metastatic prostate cancer (PCa) is now the second leading cause of cancer deaths among males in the Western countries. Radiation and androgen receptor inhibition (ARi) (i.e., pharmaceutical castration) are the standard therapy to delay PCa progression, but these conventional treatments result in a malignant selection of castration-resistant PCa clones. Previous studies described the potential use of PARPi for sensitizing radiotherapy or chemotherapy to castration-sensitive PCa in a rodent model. The recent highlighted finding is that ARi treatment down-regulates BRCA1, Rad51, Rad54 and RMI2, all are necessary for HR post-DNA DSB damage, thus indicating the acquisition of BRCAness-like phenotypes by ARi. In this review, we will describe the recent information on significance of PARPi in advanced PCa. Clinical effects are now being evaluated in patients with metastatic PCa, and some are promising. PARP1 inhibition may become a principle-based strategy for arresting metastatic PCa, if patient selection is carefully performed, on the basis of genomic (or phenotypic) detection of BRCAness.

Soft tissue sarcomas (STSs) are rare, aggressive and heterogeneous malignancies with poor outcomes. They include more than 50 different histologic subtypes with variable molecular and cytogenetic profiles responsible for the heterogeneity of these tumors. Radical surgery, chemotherapy and radiation therapy are still the mainstay of treatment with limited therapeutic options in case of metastatic and locally advanced unresectable disease. The current available cytotoxic and targeted therapies are only offering short living disease control. In the era of immunotherapy, STSs were affected by this ‘tsunami’ with very promising results, but larger randomized trials are still needed to prove their benefit in terms of survival and efficacy. They are not included yet in the standard of care. In this review of the literature, we are developing the active immunotherapeutic strategies (vaccines), as well as the passive strategies (adoptive cell therapy) and the checkpoint inhibitors emphasizing on the most recent results and on the limitation of the immunotherapy in this heterogenic media.