MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Rizikové a zhoršující faktory

Serotonin

5-HT1D receptor type

  • Involved in stimulation of cell proliferation by serotonin in human small cell lung carcinoma
  • serotonin stimulates DNA synthesis in the same cell lines
  • GLC8 cells this mitogenic effect is not counteracted by ketanserin
  • ICS 205–930 and GR 113–808 which are antagonists of the 5-HT2, 5-HT3 and 5-HT4 receptors
  • Antagonists metergoline, methysergide, SDZ 21-009 and methiothepin
    • Inhibit the 5-HT-stimulated incorporation of [3H]thymidine in GLC8 cells
  • Specific antagonists for this type of receptor might to be useful for the growth control of this very aggressive tumor.

Sumatriptan agonist and 5-HT


  • Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors
  • The 5-HT1A receptor antagonists spiperone and SDZ 216-525 completely abolished the effect of 8-OH-DPAT (IC50 30 nM for both drugs) behaving as pure antagonists.
  • pubmed.ncbi.nlm.nih.gov/8566173/

HIV medikace

  • Some of these studies have found that patients with HIV who are taking anti-HIV medication are more likely to develop SCLC than patients with HIV who are not taking anti-HIV medication. For example, one study found that the risk of developing SCLC was increased by 28% for patients with HIV who were taking anti-HIV medication.

Long exposure to carboplatin

  • Posed a “refractory” SCLC with an extremely poor prognosis, demanding participant of the second-line chemotherapy
  • Toptecan,
  • Clophosphamide,
  • Doxorubincin an
  • Vincristine
  • Were reported as the second-line SCLC’s drugs

Failed to demonstrate a survival advantage in SCLC


Nikotin and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

  • Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells
  • Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
    • Two major components in cigarette smoke
    • Significantly contribute to the development of human lung cancer
  • Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells
  • NNK is a more potent carcinogen
    • Induces single-strand DNA breaks
    • Oxidative DNA damage
    • Stimulates survival and proliferation of normal lung epithelial and lung cancer cells
  • Signaling links between nicotine/NNK and Bcl2 family members have been identified
    • Regulate survival and proliferation
  • www.semanticscholar.org/paper/Bcl2-Family-Functions-as-Signaling-Target-in-of-Deng/deb9e4d5e36ac841ad2110c22989afbe3909275f

Celecoxib

  • Cox-2 inhibitor
  • At clinically relevant concentrations promotes NSCLC cells to
    • Undergo EMT
    • Renders cell-enhanced invasive potentials
    • Chemoresistance
  • Another Cox inhibitor-induced cellular morphological change and migration via EMT in NSCLC cells
  • Evidence for interpreting the outcome of clinical studies reported previously
    • Failed to achieve survival benefit by introducing celecoxib into the conventional regimen in the NSCLC treatment.

Celecoxib and etodolac

  • Both inhibited the PGE2 synthesis
  • Celecoxib-induced EMT in A549 cells is independent of PGE2 level and Cox-2 protein
  • Selective Cox-2 inhibitor celecoxib induces epithelial-mesenchymal transition in human lung cancer cells via activating MEK-ERK signaling

CO2

  • Lung diseases that impair pulmonary oxygenation while increasing the levels of intrapulmonary carbon dioxide (CO2)
    • Documented risk factor for the development of lung cancer in smokers and nonsmokers

Cell lines derived from human small cell lung cancer (SCLC) and non-small cell lung carcinoma

  • Elevated CO2 concentrations in the range of those found in the diseased lung
    • Selectively stimulated the proliferation of SCLC but not adenocarcinoma or squamous cell carcinoma
  • Proliferative response of SCLC cells involved activation of the
    • Mitogen-activated protein kinases ERK-1 and ERK-2,
    • P70 ribosomal S6 kinase
    • Autocrine serotonergic loop
  • Kinase activation was unrelated to changes in intracellular pH.
  • CO2 is an important messenger molecule for SCLC which may contribute significantly to the high lung cancer burden observed in individuals with chronic lung disease,
  • www.sciencedirect.com/science/article/abs/pii/S0012369216317500

Poznámka:

Dechová cvičení a oxygenoterapie by mohly dávat smysl.

Corticosteroids

  • Broadly used as premedication for chemotherapy regimens and are frequently used to alleviate pain or dyspnea, to stimulate appetite
  • Corticosteroids have anti-inflammatory and immunosuppressive effects which was significantly related to worse clinical outcomes with cancer immunotherapy
  • ORR, PFS and OS were significantly worse in NSCLC patients treated with baseline steroid treatment in symptom relief as found in the report by Ricciuti et al.
  • bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-023-02754-4

Deficit selenu

The NPC trial

  • selenium supplementation may reduce risk of cancer including lung cancer
    • Among those with lower serum selenium (pod 106 ng/mL)

Study in lung cancer patients with low serum selenium (pod 70.4 ng/mL)

  • Found beneficial effects on leukopenia, hematological toxicity, and nephrotoxicity associated with cisplatin therapy
  • In the treatment of cancer, selenium may reduce toxicities and side effects associated with cisplatin and radiation therapy [41].

The results of the NPC trial and sixteen observational studies

  • Moderate but not very high selenium levels may reduce risk of lung cancer
    • Pod 106 ng/ml had significantly lower risk of lung cancer when given selenium, HR 0.42 (95%CI 0.18–0.96)
  • Those in the highest tertile (over 122 ng/ml)
    • Had non-significantly increased risk, HR 1.25 (95%CI 0.49–3.21)
    • Non-significantly increased risk with higher selenium status or supplementation in the NPC trial and four observational studies
  • selenium has its strongest chemopreventive effects in populations with lower baseline selenium status
  • Above a certain threshold it may be of limited benefit
    • 400mcg was not more effective than placebo in reducing lung cancer risk
      • Further than the 200mcg dose, to 250 ng/mL compared to 200 ng/mL by the 200mcg dose [12].

A 2004 meta-analysis of 16 observational

  • selenium had a protective effect primarily in populations where average selenium intake is low
  • Relative risk of lung cancer for highest versus lowest selenium intake groups
    • 0.74 (95% CI 0.62–0.88) (p<0.01), with high defined as over 100 ng/mL serum selenium or over 55 mcg/d dietary intake
  • Effect was significant only in areas where population serum levels were also low
    • RR 0.72 (0.56–0.93) (p<0.01),
  • Disappeared in areas where population selenium levels were higher
    • Nad 100 mcg/L or intake >55 mcg/d) RR 0.86 (0.65–1.15)
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC3208545/

Down-regulation of P-Glycoprotein

  • Associated with Resistance to Cisplatin and VP-16 in Human Lung Cancer Cell Lines

EP4 agonist (PGE1 alcohol)

Poznámka:

  • Dohledat, které další látky jsou aktivátory EP4 receptoru = rizikové

Glukóza, hyperglykémie



Mléko a mléčné výrobky

  • Několik studií, které naznačují, že konzumace mléka a mléčných výrobků může být spojena s vyšším rizikem vzniku některých typů rakoviny, včetně malobuněčného karcinomu plic.
  • Studie z roku 2022, v časopise Cancer Causes & Control
    • Lidé, kteří konzumovali více mléka a mléčných výrobků
      • Měli vyšší riziko vzniku malobuněčného karcinomu plic.
      • Více než 1 000 lidí po dobu pěti let
      • Nejvíce mléka a mléčných výrobků, měli o 20 % vyšší riziko vzniku malobuněčného karcinomu plic
        • Než ti, kteří konzumovali nejméně mléka a mléčných výrobků.
  • Studie, v časopise Cancer Epidemiology, Biomarkers & Prevention v roce 2021
    • Lidé, kteří konzumovali více mléka a mléčných výrobků
      • Měli vyšší riziko recidivy malobuněčného karcinomu plic.
    • Studie sledovala více než 1 000 lidí po dobu pěti let
      • Konzumovali nejvíce mléka a mléčných výrobků, měli o 30 % vyšší riziko recidivy malobuněčného karcinomu plic
        • Než ti, kteří konzumovali nejméně mléka a mléčných výrobků.
  • Závěry těchto studií naznačují, že konzumace mléka a mléčných výrobků může zvýšit riziko vzniku a recidivy malobuněčného karcinomu plic.
  • Mezi možné mechanismy, kterými by mléko a mléčné výrobky mohly zvýšit riziko vzniku rakoviny, patří:
    • Mléko a mléčné výrobky obsahují
    • Hormony, které mohou ovlivnit růst a šíření rakovinných buněk.
    • IGF-1 je růstový faktor, který může podporovat růst rakovinných buněk. Mléko a mléčné výrobky obsahují IGF-1.
    • Prozánětlivé faktory, které mohou poškodit DNA buněk a zvýšit riziko vzniku rakoviny.
  • Lidé s malobuněčným karcinomem plic by měli omezit konzumaci mléka a mléčných výrobků.
Bard Gogle Gemini


PEG2



PPI

Proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis.

  • 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy retrospectively analyzed
  • Divided into PPI group and control group
  • Effects of different doses of PPI on patient condition from two groups were compared
  • 57 cases in PPI group
  • 27 cases in control group
  • White blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05)
    • Radiation pneumonitis tended to be more severe in PPI group
  • PPI on prognosis of two groups
    • Remission rate of radiation pneumonia in PPI group was significantly less than that of the control group
  • Among 57 cases in PPI group (???)
    • 31 patients applied with PPI pod 1DDD
    • 31 patients applied with PPI nad 1DDD
  • 7 days after being applied with different doses of PPI
    • no significant differences between the parameters of radiation pneumonitis
  • PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC4182645/

Platinum sensitivity / resistance

  • I’m thinking about lurbinectedin as my second-line option
    • I can always go back to a platinum doublet later
  • I’ve given lurbinectedin straight up to patients who would have otherwise met all the criteria for re-treatment with platinum. If you do that enough times
  • They may stack up similarly
  • Probably just a matter of whether these tumors have undergone EMT [epithelial-mesenchymal transition] or whatever their resistance mechanism is going to prevent them from responding to cytotoxic therapy
    • It’s not about the platinum at all.
  • www.onclive.com/view/treatment-options-for-relapsed-small-cell-lung-cancer

Polyamines (putrescine, spermidine, and spermine) are increased



Mohou stimulovat růst

  • Potraviny s vysokým obsahem tuku, zejména nasyceného a transtuků
  • Potraviny s vysokým obsahem cukru
    • Cukr může podporovat růst nádorů a také oslabovat imunitní systém.
  • Potraviny s vysokým obsahem soli
    • Sůl může poškodit sliznice v těle, což může usnadnit rakovinným buňkám šíření.
  • Potraviny s vysokým obsahem rafinovaných sacharidů
    • Rafinované sacharidy mohou způsobovat zánět, který může podporovat růst rakoviny.
  • Potraviny s vysokým obsahem červeného masa
    • Červené maso obsahuje látky, které mohou podporovat růst rakoviny, zejména karcinomu plic.
    • Salámy a jiné uzeniny
    • Sýry s vysokým obsahem tuku
    • Krémové polévky a omáčky
    • Sladkosti, včetně cukrovinek, zmrzliny a pečiva
    • Potraviny s vysokým obsahem soli, jako jsou konzervované potraviny, slané pochutiny a fast food
  • Lidé s malobuněčným karcinomem plic by se měli také vyhýbat alkoholu
    • Protože může zvýšit riziko recidivy rakoviny.
  • Studie z roku 2022, v časopise Cancer Epidemiology, Biomarkers & Prevention
    • Lidé, kteří konzumovali větší množství červeného masa, měli vyšší riziko vzniku malobuněčného karcinomu plic
    • Více než 100 000 lidí po dobu 20 let
      • Nejvíce červeného masa, měli o 20 % vyšší riziko vzniku malobuněčného karcinomu plic než ti, kteří konzumovali nejméně červeného masa.
  • Studie, v časopise Cancer Causes & Control v roce 2021
    • Lidé, kteří konzumovali více červeného masa, měli vyšší riziko recidivy malobuněčného karcinomu plic
    • Více než 1 000 lidí po dobu pěti let
      • Nejvíce červeného masa, měli o 30 % vyšší riziko recidivy malobuněčného karcinomu plic než ti, kteří konzumovali nejméně červeného masa.
  • Závěry těchto studií naznačují, že konzumace červeného masa může zvýšit riziko vzniku a recidivy malobuněčného karcinomu plic.
    • Studie jsou pouze asociační
    • Nedokážou prokázat, že červené maso přímo způsobuje malobuněčný karcinom plic.
    • Nicméně poskytují důkazy, že konzumace červeného masa může být rizikovým faktorem pro tento typ rakoviny.
Google Bart Gemini


Proton-pump inhibitors

Nationwide population-based study

  • Increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment
  • Concurrent use of PPIs was associated with lower overall survival in patients with EGFR-mutant NSCLC under first-line gefitinib treatment.
  • Risk of mortality increased 21% within 90 days
    • Among patients with lung cancer who were receiving erlotinib with a concomitant PPI.
  • Treatment with other TKIs like sunitinib and imatinib had no significant association between the risk of death and concomitant TKI-PPI treatment.
  • Despite the recommendation of the US Food and Drug Administration (FDA) to avoid concomitant use of gefitinib with PPIs, we found that 24.17% patients with lung cancer taking first-line gefitinib received PPIs at the same time.
  • Anti-acid-secreting agents increased gefitinib-induced hepatotoxicity about 1.5- to 1.7-fold.23 Furthermore, PPIs inhibit gastric acid secretion and increase the intra-gastric pH, leading to gut dysbiosis and an increased risk of enteric infection and diarrhea.24 This can partially explain the increased incidence of diarrhea and infections in patients enrolled in the BR21 study receiving gastric acid suppression medications during treatment with erlotinib.
  • Co-administration of PPIs decreases the absorption of EGFR-TKIs, CSF concentration of EGFR-TKIs would likely further reduce to an insufficient level
  • For patients receiving first-line EGFR-TKIs and PPIs, taking gefitinib or erlotinib with an acidic beverage like soda could be an alternative choice.
  • www.dovepress.com/concurrent-proton-pump-inhibitors-increase-risk-of-death-for-lung-canc-peer-reviewed-fulltext-article-CMAR

Proton Pump Inhibitor + Pembrolizumab Monotherapy - vs Immune Checkpoint Inhibitor + Chemotherapy

  • In Patients With Non-Small Cell Lung Cancer
  • Cohort study of 425 patients with advanced non–small cell lung cancer
  • A history of proton pump inhibitor (PPI) use was associated with
    • Shorter progression-free survival.
    • Progression-free survival and overall survival were significantly longer in the ICI + chemotherapy group than in the ICI pembrolizumab monotherapy group.
  • These findings suggest that a history of concomitant PPI use may be an important clinical factor that should be considered when choosing an ICI treatment with or without chemotherapy.
  • 13 hospitals in Japan included patients with advanced NSCLC with a PD-L1 TPS of 50% or more
    • Received pembrolizumab ICI monotherapy or ICI plus chemotherapy as the initial treatment
    • The median (IQR) follow-up duration was 18.5 (9.2-31.2) months.

425 patients with NSCLC

  • 271 patients median [range] age, 72 [43-90] years;
    • 215 [79%] men treated with pembrolizumab monotherapy as the first-line treatment
    • 154 patients (median [range] age, 69 [36-86] years; 121 [79%] men) who were treated with ICI plus chemotherapy as the first-line treatment
  • History of proton pump inhibitor (PPI) use
    • Independently associated with shorter progression-free survival (PFS) in the pembrolizumab monotherapy group
      • (hazard ratio [HR], 1.38; 95% CI, 1.00-1.91; P = .048),
    • But not in the ICI plus chemotherapy group
  • In patients with a PPI history
    • Median (IQR) PFS (19.3 [9.0 to not reached] months vs 5.7 [2.4 to 15.2] months; HR, 0.38; 95% CI, 0.20-0.72; P = .002)
    • Median (IQR) overall survival (not reached [9.0 months to not reached) vs 18.4 [10.5 to 50.0] months; HR, 0.43; 95% CI, 0.20-0.92; P = .03)
    • Were significantly longer in the ICI plus chemotherapy group than in the pembrolizumab monotherapy group
  • In patients without a history of PPI use
    • Both the median (IQR) PFS (18.8 months [6.6 months to not reached] vs 10.6 months [2.7 months to not reached]; HR, 0.81; 95% CI, 0.56-1.17; P = .26)
    • Median (IQR) overall survival (not reached [12.6 months to not reached] vs 29.9 [13.3 to 54.3] months, HR, 0.75; 95% CI, 0.48-1.18; P = .21) did not differ between groups.
  • jamanetwork.com/journals/jamanetworkopen/fullarticle/2807132
  • PPIs may have pro-tumor activity
    • By increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases
  • PPIs may decrease the efficacy of some antineoplastic agents
    • Through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate).
  • More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome.
  • PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies
  • May have a protective effect on the renal system.
  • May interact with the cancer microbiome and the efficacy of various antineoplastic agents
  • www.frontiersin.org/articles/10.3389/fphar.2022.798272/full
  • PPIs therapy has a negative impact on the clinical outcomes of advanced SCLC patients treated with PD-L1 inhibitors

208 patients, 101 received immunotherapy concomitant PPIs

  • Median PFS of patients receiving PPIs (6.6 months) were significantly shorter
  • Than those without PPIs (10.6 months)
  • Both first-line and post-first-line immunotherapy, patients treated PPIs had poorer PFS.
  • PPI associated with a
    • 74.9% increased risk of progression
    • 58.3% increased risk of death.
  • bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-023-02754-4


  • Polycyclic aromatic hydrocarbons,
  • N-nitrosamines,
  • Aromatic amines
  • Undecane,
  • Pyrene,
  • Fluoranthene,
  • Carcinogenicity of cigarette smoke carcinogens
  • Smokers that are closely associated with tumor promotion and NF-kappaB signaling
  • Nitrogen dioxide
  • acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21785

Largest risk factor for developing SCLC


Rizikové faktory vzniku

  • Smoking cigarettes, pipes, or cigars
  • Exposed to secondhand smoke.
  • Exposed to asbestos, arsenic, chromium, beryllium, nickel, soot, or tar in the workplace.
  • Exposed to radiation from any of the following:
    • Radiation therapy to the breast or chest.
    • Radon in the home or workplace.
    • Imaging tests such as CT scans.
    • Atomic bomb radiation.
  • Living where there is air pollution.
  • Family history of lung cancer.
  • Human immunodeficiency virus (HIV).
  • Beta carotene supplements and being a heavy smoker
  • www.cancer.northwestern.edu/types-of-cancer/lung/small-cell-lung-cancer.html

Smoking

  • Cumulative duration and intensity of smoking
  • More than 90% of patients are elderly heavy current or ex-smokers
    • With various pulmonary, cardiovascular, and metabolic comorbidities
  • Elderly patients older than 70 years
    • Inferior outcomes compared to younger patients
    • Less likely to be subjected to conventional treatments

Unique molecular subtypes of SCLC


Zvýšená hladina vápníku

  • Zvyšuje proliferaci nádoru
  • Takže konzumace mléčných výrobků, málo vitamínu D s vyšším parathormonem a málo vitamínu K dá výsledek nepříznivý

Extracellular Ca2+



Vitamín B12

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O úroveň výše

Poslední aktualizace: 10. 12. 2023 2:02:10