يتمتع الدكتور أشوك سيث ، أفضل جراح لإصلاح الصمام التاجي ، بخبرة واسعة في جراحة القلب والرعاية الجراحية الحرجة. مواكبة التكنولوجيا المتقدمة تتيح لفريقه توفير أفضل رعاية لحالة قلبك الفريدة ، حيث يجري أكثر من 1600 عملية جراحية سنويًا في الهند.
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surgery per se can promote cancer metastasis through a series of local and systemic events
surgery results in a serious wound that disrupts the structural barrier preventing the outspreading of cancer cells, change the properties of the cancer cells and stromal cells remaining in the tumor microenvironment, or impairs the host defense systems against cancers
Key point; add to presentation on surgery and metastasis
After the primary tumor is surgically removed, the metastases can start to grow vigorously via neoangiogenesis because the circulating inhibitors disappear
infection and inflammation during the postoperative period have been reported to increase the risk of cancer recurrence in patients
Surgeons have long suspected that surgery, even if it is a necessary step in cancer treatment, facilitates cancer metastasis
Surgery-induced cancer metastasis has been well established in animal models
tumor cell dissemination, tumor-favoring immune responses, and neoangiogenesis
the surgical resection of primary tumors is beneficial is controversial
CTCs abruptly increase just after surgery
Even externally palpitating tumors for diagnosis could increase the numbers of CTCs in skin cancer and breast cancer
immune surveillance against tumors is considered to be impaired by surgical stress
In addition to glucocorticoids, during stimulation of the HPA axis, the catecholamine hormones epinephrine and norepinephrine are released from the adrenal medulla
NK cell suppression may be attributed to increased levels of catecholamines as well as glucocorticoids
In mice bearing a primary tumor, it was observed that the removal of the primary tumor facilitated the growth of highly vascularized metastases
primary tumors may secrete angiogenic inhibitors as well as angiogenic activators
second phase of tumor recurrence and metastasis, which are newly acquired events, rather than just outcomes of incomplete treatment.
HIF-1 in neutrophils plays a critical role in NETosis and bacteria-killing activity
neutrophils play various roles in the initiation and progression of cancer
NETosis
many inflammatory and neoplastic diseases
formation of neutrophil extracellular traps (NETs), which are large extracellular complexes composed of chromatin and cytoplasmic/granular proteins1
NETosis has been highlighted as an inflammatory event that promotes cancer metastasis
Once activated, neutrophils produce intracellular precursors by using DNA, histones, and granular and cytoplasmic proteins and then spread the mature form of NETs out around themselves
Neutrophils are the most abundant type of granulocytes, comprising 40–70% of all white blood cells
two types of NEToses, suicidal (or lytic) NETosis and vital NETosis
Suicidal NETosis mainly depends on the production of reactive oxygen species (ROS)
Since neutrophils die during this process, it is called suicidal NETosis.
vital NETosis
vital NETosis occurs independently of ROS production
Vital NETosis can be induced by Gram-negative bacteria. LPS
NETs are present in a variety of cancers, such as lung cancer, colon cancer, ovarian cancer, and leukemia
neutrophils actively undergo NETosis in the tumor microenvironment
Hypoxia
NETosis plays a pivotal role in noninfectious autoimmune diseases,
cytokines
tumor-derived proteases
tumor exosomes
NETosis generally actively progresses in the tumor microenvironment.
the proliferative cytokines TGFβ and IL-10 and the angiogenic factor VEGF are representative of neutrophil-derived tissue repair proteins.
NETosis is a defense system to protect the body from invading pathogens
when neutrophils are excessively stimulated, they produce excess NETs, thereby leading to pathological consequences
plasma levels of NETosis markers are elevated after major surgeries
local invasion, intravasation into the blood or lymphatic vessels, escape from the immune system, anchoring to capillaries in target organs, extravasation into the organs, transformation from dormant cells to proliferating cells, colonization to micrometastases, and growth to macrometastases
NETs promote metastasis at multiple steps
NETs loosen the ECM and capillary wall to promote the intravasation of cancer cells
NETs and platelets wrap CTCs, which protects them from attack by immune cells and shearing force by blood flow
NETs promote the local invasion of cancer cells by degrading the extracellular matrix (ECM)
neutrophil elastase, matrix metalloproteinase 9, and cathepsin G
NETs also promote the intravasation of cancer cells
millions of tumor cells are released into the circulation every day,
NETs can wrap up CTCs with platelets
β1-integrin plays an important role in the interaction between CTCs and NETs
NET-platelet-CTC aggregates.
After metastasizing to distant tissues, tumor cells are often found to remain dormant for a period of time and unexpectedly regrow late
NETs are believed to participate in the reactivation of dormant cancer cells in metastatic regions
NET-associated proteases NE and MMP-9 were found to be responsible for the reactivation of dormant cancer cells
daily doses up to 400 mg of HCQ or 250 mg CQ for several years are considered to carry an acceptable risk for CQ-induced retinopathies, with the exception of individuals of short stature
chronic CQ or HCQ therapy be monitored through regular ophthalmic examinations (3–6 month intervals), full blood counts and blood glucose level checks
long-term HCQ exposure, skeletal muscle function and tendon reflexes should be monitored for weakness
both CQ and HCQ, specific caution is advised in patients suffering from impaired hepatic function (especially when associated with cirrhosis), porphyria, renal disease, epilepsy, psoriasis, glucose-6-phosphate dehydrogenase deficiency and known hypersensitivity to 4-aminoquinoline compounds
CQ and HCQ can effectively increase the efficacy of various anti-cancer drugs
CQ can prevent the entrapment of protonated chemotherapeutic drugs by buffering the extracellular tumour environment and intracellular acidic spaces
This study recommends an adjuvant HCQ dose of 600 mg, twice daily.
HCQ addition was shown to produce metabolic stress in the tumours
HCQ (400 mg/day)
important effects of CQ and HCQ on the tumour microenvironment
The main and most studied anti-cancer effect of CQ and HCQ is the inhibition of autophagy
the expression levels of TLR9 are higher in hepatocellular carcinoma, oesophageal, lung, breast, gastric and prostate cancer cells as compared with adjacent noncancerous cells, and high expression is often linked with poor prognosis
TLR9-mediated activation of the NF-κB signalling pathway and the associated enhanced expression of matrix metalloproteinase-2 (MMP-2), MMP-7 and cyclo-oxygenase 2 mRNA
HCQ can activate caspase-3 and modulate the Bcl-2/Bax ratio inducing apoptosis in CLL, B-cell CLL and glioblastoma cells
In triple-negative breast cancer, CQ was shown to eliminate cancer stem cells through reduction of the expression of Janus-activated kinase 2 and DNA methyl transferase 1 [106] or through induction of mitochondrial dysfunction, subsequently causing oxidative DNA damage and impaired repair of double-stranded DNA breaks
CQ or HCQ would be considered for use in combination with immunomodulation anti-cancer therapies
Therapies used in combination with CQ or HCQ include chemotherapeutic drugs, tyrosine kinase inhibitors, various monoclonal antibodies, hormone therapies and radiotherapy
Most studies hypothesise that CQ and HCQ could increase the efficacy of other anti-cancer drugs by blocking pro-survival autophagy.
daily doses between 400 and 1200 mg for HCQ are safe and well tolerated, but two studies identified 600-mg HCQ daily as the MTD
HCQ is often administered twice daily to limit plasma fluctuations and toxicity
تعتبر المستشفيات الكبرى لإصلاح صمام القلب في الهند رائدة في تقديم رعاية قلب رائعة بشكل استثنائي. قامت معظم المستشفيات الكبرى لإصلاح صمام القلب في الهند بدمج التكنولوجيا المتقدمة التي تساعد في تحقيق معدلات نجاح أعلى.
اتصل بنا على + 91-9370586696 أو راسلنا عبر البريد الإلكتروني على enquiry@indiacardiacsurgerysite.com