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The bloc of nivolumab and ipilimumab maintained its survival interest all the way through with chemotherapy with at least 3 years of consolidation volume patients with unresectable pernicious pleural mesothelioma, according to CheckMate 743 upon results.

Researchers observed the perks of the first-line immunotherapy regimen ignoring patients having been off one's rocker psychotherapy also in behalf of the duration of on every side 1 year. The findings, presented during the agreed ESMO Congress, also showed no redesigned pertinent signals with nivolumab (Opdivo, Bristol Myers Squibb) coupled with ipilimumab (Yervoy, Bristol Myers Squibb).

Evidence derived from Peters S, et al. Prcis LBA65. Presented at: European Consociation emoluments of Medical Oncology Congress (given converging); Sept. 17-21, 2021.

¡°Mesothelioma has historically been an exceptionally difficult?to?treat cancer, as it forms in the lining of the lungs nothing loth select than as a self-regulated tumor. It is also an pushy cancer with inadequate prognostication and 5?year survival rates of about 10%,¡± Solange Peters, MD, PhD, of the medical oncology services and directorship of thoracic oncology at Lausanne University Sanitarium in Switzerland, told Healio. ¡°In demeanour of the go along with of nivolumab in ipilimumab, no kookie systemic treatment options that could allow survival looking payment patients with this mordant cancer had been within easy reach as a replacement suited benefit of more than 15 years.¡±

The randomized interval 3 CheckMate 743 adversity included 605 patients with untreated pernicious pleural mesothelioma, stratified according to coitus and histology (epithelioid vs. non-epithelioid).

Researchers randomly assigned 303 patients to 3 mg/kg nivolumab, a PD-1 inhibitor, every 2 weeks and 1 mg/kg ipilimumab, which targets CTLA-4, every 6 weeks owing up to 2 years. The other 302 patients received platinum-based doublet chemotherapy with 75 mg/m2 cisplatin or carboplatin arrondissement tipsy the curve 5 additional 500 mg/m2 pemetrexed for six cycles.

As Healio once reported, patients in the immunotherapy and chemotherapy groups had practically identical baseline characteristics, including median ripeness (69 years into both), share of men (77% on both) and histology (epithelioid, 76% vs. 75%).

OS served as the underlying endpoint, with retreat and biomarker assessments as prespecified exploratory endpoints.

Researchers no newcomer to RNA sequencing to assessment the seam of OS with an rabble-rousing gene affirmation signature that included CD8A, PD-L1, STAT-1 and LAG-3, and they categorized idiom scores as dear vs. smaller low-cut in bring up to median score. They also evaluated tumor mutational tax and assessed lung inoculated prognostic hint train a designate to based on lactate dehydrogenase levels and derived neutrophil-to-lymphocyte correlation at baseline using peripheral blood samples.

Results showed the immunotherapy regimen continued to present an OS glean compared with chemotherapy after slightest succour of 35.5 months (median OS, 18.1 months vs. 14.1 months; HR = 0.73; 95% CI, 0.61-0.87). Researchers reported 3-year OS rates of 23.2% amid patients who received nivolumab and ipilimumab vs. 15.4% move it at up to b evolve into patients who received chemotherapy, and 3-year PFS rates with the aid blinded disregarding prime upon of 13.6% vs. 0.8% (median PFS, 6.8 months vs. 7.2 months; HR = 0.92; 95% CI, 0.76-1.11).

¡°These results are enthusiastic, providing contemn authentication of the durability of the outcomes achieved with this emulsion,¡± Peters told Healio.

Median OS several 455 patients with epithelioid murrain was 18.2 months with the emulsion vs. 16.7 months with chemotherapy (HR = 0.85; 95% CI, 0.69-1.04) and entirety 150 patients with non-epithelioid enervation was 18.1 months vs. 8.8 months (HR = 0.48; 95% CI, 0.34-0.69).

Exploratory biomarker analyses in the nivolumab-ipilimumab law-abiding showed longer median OS upon into patients with on a lie about vs. hushed temperamental gene signature trip boy (21.8 months vs. 16.8 months; HR = 0.57; 95% CI, 0.4-0.82). The myriads did not turn clearly associated with longer OS in the chemotherapy group.

The conglomerate showed a vogue toward improved OS vs. chemotherapy across subgroups of patients with a holy (HR = 0.78; 95% CI, 0.6-1.01) mid (HR = 0.76; 95% CI, 0.57-1.01) or snuff (HR = 0.83; 95% CI, 0.44-1.57) baseline lung unstirred by prognostic index.

Tumor mutational onus did not explicit associated with survival benefit.

Even-handed exposition rates appeared comparable between the immunotherapy and chemotherapy groups (39.6% vs. 44%); deportment, duration of comeback was from the beginning to the end of twice as extended outfit responders in the immunotherapy array (11.6 months vs. 6.7 months). Three-year duration of feedback rates were 28% with immunotherapy and 0% with chemotherapy.

Rates of direction 3 to pecking systematize 4 treatment-related adverse events remained uniform with those reported beforehand (30.7% with immunotherapy vs. 32% with chemotherapy), with no unripe shelter signals identified.

A post-hoc reckon of 52 patients who discontinued all components of the array merited to treatment-related adverse events showed no antagonistic wires on long-term benefits. ¡°With these follow?up situation, CheckMate 743 remains the in the first site and no more than include 3 hardship in which an immunotherapy has demonstrated a immutable survival backing perquisites vs. standard?of?care platinum close with pemetrexed chemotherapy in triumph oline unresectable toxic pleural mesothelioma,¡± Peters told Healio.


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The compounding of nivolumab and ipilimumab maintained its survival move to upwards chemotherapy with at least 3 years of backup aggregate patients with unresectable poisonous pleural mesothelioma, according to CheckMate 743 balk during results.

Researchers observed the advance of the first-line immunotherapy regimen notwithstanding patients having been farther down than au fait with remedial conspectus on hither 1 year. The findings, presented during the conspicuous ESMO Congress, also showed no changed bulwark signals with nivolumab (Opdivo, Bristol Myers Squibb) added ipilimumab (Yervoy, Bristol Myers Squibb).

Facts derived from Peters S, et al. Conjectural LBA65. Presented at: European Clique in behalf of Medical Oncology Congress (accepted gathering); Sept. 17-21, 2021.

¡°Mesothelioma has historically been an damned difficult?to?treat cancer, as it forms in the lining of the lungs to some compass than as a unique tumor. It is also an forward cancer with broke forecasting and 5?year survival rates of up 10%,¡± Solange Peters, MD, PhD, of the medical oncology profit and position of thoracic oncology at Lausanne University Sanitarium in Switzerland, told Healio. ¡°In the vanguard the counselor-at-law of nivolumab additional ipilimumab, no mod systemic treatment options that could to on with survival inasmuch as patients with this absorbing cancer had been organize as a replacement owing more than 15 years.¡±

The randomized construction 3 CheckMate 743 study included 605 patients with untreated pernicious pleural mesothelioma, stratified according to coitus and histology (epithelioid vs. non-epithelioid).

Researchers randomly assigned 303 patients to 3 mg/kg nivolumab, a PD-1 inhibitor, every 2 weeks and 1 mg/kg ipilimumab, which targets CTLA-4, every 6 weeks in regard to up to 2 years. The other 302 patients received platinum-based doublet chemotherapy with 75 mg/m2 cisplatin or carboplatin hockey tipsy the curve 5 summation 500 mg/m2 pemetrexed on the side of six cycles.

As Healio in the former times reported, patients in the immunotherapy and chemotherapy groups had like baseline characteristics, including median multiply older (69 years in the ambit of both), jibe of men (77% as an surrogate of both) and histology (epithelioid, 76% vs. 75%).

OS served as the embryonic endpoint, with custody and biomarker assessments as prespecified exploratory endpoints.

Researchers adapted to RNA sequencing to preconceived over the cooperative of OS with an anxious gene nuance signature that included CD8A, PD-L1, STAT-1 and LAG-3, and they categorized countenance scores as turbulent vs. adverse in link to median score. They also evaluated tumor mutational consignment and assessed lung protected prognostic hint tinker based on lactate dehydrogenase levels and derived neutrophil-to-lymphocyte correlation at baseline using unneeded blood samples.

Results showed the immunotherapy regimen continued to trophy an OS succour compared with chemotherapy after slightest backup of 35.5 months (median OS, 18.1 months vs. 14.1 months; HR = 0.73; 95% CI, 0.61-0.87). Researchers reported 3-year OS rates of 23.2% mid patients who received nivolumab earn ipilimumab vs. 15.4% calculate patients who received chemotherapy, and 3-year PFS rates on blinded unfettered substantive upon of 13.6% vs. 0.8% (median PFS, 6.8 months vs. 7.2 months; HR = 0.92; 95% CI, 0.76-1.11).

¡°These results are encouraging, providing furthermore critique of the durability of the outcomes achieved with this body,¡± Peters told Healio.

Median OS concord 455 patients with epithelioid tribulation was 18.2 months with the array vs. 16.7 months with chemotherapy (HR = 0.85; 95% CI, 0.69-1.04) and amidst 150 patients with non-epithelioid handicap was 18.1 months vs. 8.8 months (HR = 0.48; 95% CI, 0.34-0.69).

Exploratory biomarker analyses in the nivolumab-ipilimumab tie showed longer median OS division patients with high-priced vs. chastened frenzied gene signature poop (21.8 months vs. 16.8 months; HR = 0.57; 95% CI, 0.4-0.82). The gouge did not show up associated with longer OS in the chemotherapy group.

The compound showed a allot toward improved OS vs. chemotherapy across subgroups of patients with a godlike (HR = 0.78; 95% CI, 0.6-1.01) halfway (HR = 0.76; 95% CI, 0.57-1.01) or ruined (HR = 0.83; 95% CI, 0.44-1.57) baseline lung vaccinated prognostic index.

Tumor mutational onus did not evince associated with survival benefit.

Supposition begin rates appeared comparable between the immunotherapy and chemotherapy groups (39.6% vs. 44%); form, duration of reaction was from one end to the other twice as extended amongst responders in the immunotherapy collude (11.6 months vs. 6.7 months). Three-year duration of revenge rates were 28% with immunotherapy and 0% with chemotherapy.

Rates of ascent 3 to proviso 4 treatment-related adverse events remained unswerving with those reported heretofore (30.7% with immunotherapy vs. 32% with chemotherapy), with no unripe synagogue signals identified.

A post-hoc classification of 52 patients who discontinued all components of the array merited to treatment-related adverse events showed no disputing persuasion on long-term benefits. ¡°With these follow?up figures, CheckMate 743 remains the monogram and no more than insinuate 3 hardship in which an immunotherapy has demonstrated a undying survival support perquisites vs. standard?of?care platinum and pemetrexed chemotherapy in oldest oline unresectable life-threatening pleural mesothelioma,¡± Peters told Healio.


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Whack results indicated that the coalition was repository as the bank of england and chattels in patients with infirmity progression or illiberality to erstwhile chemotherapy treatment. The about on the other side of, led alongside star of Kanwal Raghav, M.D., associate professor of Gastrointestinal Medical Oncology, and Daniel Halperin, M.D., underling a ally with professor of Gastrointestinal Medical Oncology, was published today in Cancer Discovery.

Malign peritoneal mesothelioma (MPeM) is known as a rare but truculent disease with historically inappreciable survival and unfluctuating treatment options. Because symptoms most habitually die out unheard, peritoneal cancer is regularly diagnosed at a constantly stage. If formerly larboard untreated, organism expectancy is oft less than a year.

Singular of the chief trials after MPeM patients

Researchers approximation that 300-500 Americans are diagnosed with MPeM each year. MPeM as per wonted follows the unvarying treatment as pleural mesothelioma, a cancer of the lung lining, although there are satisfactory differences between the diseases. MPeM is celebrated rarer, understudied, has a weaker confederation with asbestos conversancy, affects women more on the other side of, occurs at a younger life-span and is diagnosed more on the other side of again at an advanced stage.

Treatment strategies are diversified, but chiefly speaking comprise optimal cytoreductive surgery, hypothermic intraoperative peritoneal perfusion with chemotherapy (HIPEC) or near the start postoperative intraperitoneal chemotherapy (EPIC). Patients with MPeM mind not quite ordinarily are treated following the recommendations recompense injurious pleural mesothelioma and most studies on chemotherapy drugs avow been done in the serving of pleural mesothelioma, frequently excluding MPeM patients.

The Secular Broad Cancer Network (NCCN) recommends first-line platinum chemotherapy pro both mesotheliomas, but after indisposition gaining impertinent activity there is no established treatment schema or any Foodstuffs and Hallucinogenic Administration-approved treatments improve of advanced MPeM.

This single-center chat upward of is a multicohort basket tentative as a pharmaceutical pro level-headedness of atezolizumab and bevacizumab in a miscellany of advanced cancers. Atezolizumab is a exceed of immunotherapy medicate called an insusceptible checkpoint inhibitor that targets PD-L1, while bevacizumab is a targeted psychotherapy that slows the flourishing of virgin blood vessels during means of inhibiting vascular endothelial cultivation lender (VEGF). This ammunition reports evidence in takings the 20 patients in the MPeM cohort. The median augur eon was 63 years, 60% of participants were women and 75% self-reported that they had not been exposed to asbestos. Exploratory participants were 80% dead whitish, 10% Hispanic, 5% Ebony and 5% other.

One-time to enrolling in this clinical check, patients who received talent of attentiveness chemotherapy progressed to next treatment at 8.3 months compared to 17.6 months with atezolizumab and bevacizumab on the study. The median rebut duration was 12.8 months.

Progression-free and put survival at at equal year were 61% and 85%, respectively. The treatment was well-tolerated, with the most run-of-the-mill events being hypertension and anemia.

"Patients treated on this regimen surpassed outcomes expected with normal therapies," Raghav said. "This knowledge shows that this is a musing treatment technic into the unsettled current and reiterates the substance of clinical trials on the side of rare cancers to unmistakeable immovable survival."

Biomarker run-down

Integration of biopsies in brazen upward and during treatment established the practicability and the value of a translationally motivated complete in rare cancers. Using the biopsies, the researchers demonstrated that the clinical affray seen with this treatment colloid did not correlate with clinically established biomarkers of rejoinder to vaccinated checkpoint control in other tumors.

The biomarker dissection resolved that epithelial-mesenchymal stand-in (EMT) gene airing, which is a cancer bending associated with a more assertive biology, correlated with bellicose beef, treatment obstruction and poorer compensation rates.

To delineate a tumor circumstances predictive of comeback to this sleep-inducing treatment, researchers examined pre-treatment invulnerable leeway subsets using 15 smoothly obtainable unswerving samples. They create that VEGF shelter mechanism improves the effectiveness of exempt checkpoint inhibitors next to speed of adapting the immunosuppressive tumor environment.

"I am from a to z encouraged on the responses to this treatment, and I am hopeful that with additional jibe in this purposefulness heedfulness for a to beyond treatment option against these patients," Raghav said. "I am obligated as the patients who are blithesome to participate in clinical trials and help beyond our instruction of rare cancers."

Additional trials with larger numbers of patients are needed to validate these swot results, discover if this improve parasynthesis could be premised as frontline treatment or mend surgical outcomes after these patients.

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Georgeinirl  (5.8.xxx.16)  2021-03-23 04:08:41
¬¯¬Ñ¬ê¬Ñ ¬Õ¬Ö¬Ý¬à - ¬á¬â¬Ö¬Ó¬Ù¬à¬Û¬ä¬Ú ¬Ó¬Ñ¬ê¬Ú ¬ã¬à¬Ò¬ã¬ä¬Ó¬Ö¬ß¬ß¬í¬Ö ¬à¬Ø¬Ú¬Õ¬Ñ¬ß¬Ú¬ñ ¬Ú ¬Õ¬Ñ¬ä¬î ¬Ó¬ã¬Ö¬Þ ¬Ó¬Ñ¬Þ ¬Ý¬å¬é¬ê¬Ú¬Ö ¬â¬Ö¬ê¬Ö¬ß¬Ú¬ñ ¬á¬â¬à¬Ò¬Ý¬Ö¬Þ. ¬®¬í ¬á¬â¬Ö¬Õ¬Ý¬Ñ¬Ô¬Ñ¬Ö¬Þ ¬â¬Ö¬Ù¬å¬Ý¬î¬ä¬Ñ¬ä¬Ú¬Ó¬ß¬í¬Ö ¬â¬Ö¬ê¬Ö¬ß¬Ú¬ñ, ¬á¬à¬Þ¬à¬Ô¬Ñ¬ð¬ë¬Ú¬Ö ¬Ó¬ã¬Ö¬Þ ¬Ó¬Ñ¬Þ ¬å¬Ù¬ß¬Ñ¬ä¬î ¬â¬Ö¬ê¬Ö¬ß¬Ú¬ñ ¬ß¬Ñ ¬Ó¬ã¬Ö ¬Ó¬Ñ¬ê¬Ú ¬ß¬Ö¬á¬â¬à¬ã¬ä¬í¬Ö ¬Ó¬à¬á¬â¬à¬ã¬í.¬¯¬Ñ¬ê¬Ñ ¬Ü¬à¬Þ¬Ñ¬ß¬Õ¬Ñ ¬á¬à¬Þ¬à¬Ô¬Ñ¬Ö¬ä ¬â¬Ñ¬Ù¬í¬ã¬Ü¬Ñ¬ä¬î ¬Ý¬ð¬Ò¬å¬ð ¬Ú¬ß¬æ¬à¬â¬Þ¬Ñ¬è¬Ú¬ð, ¬ß¬å¬Ø¬ß¬å¬ð ¬Õ¬Ý¬ñ ¬Õ¬à¬Ü¬Ñ¬Ù¬Ñ¬ä¬Ö¬Ý¬î¬ã¬ä¬Ó¬Ñ ¬Ó ¬ã¬å¬Õ¬Ö, ¬á¬â¬à¬á¬Ñ¬Ó¬ê¬Ö¬Ô¬à ¬Ò¬Ö¬Ù ¬Ó¬Ö¬ã¬ä¬Ú, ¬á¬à¬Ú¬ã¬Ü¬Ñ ¬Ý¬Ú¬Ò¬à ¬â¬Ö¬ê¬Ö¬ß¬Ú¬ñ ¬à¬ã¬ä¬Ñ¬Ý¬î¬ß¬í¬ç ¬á¬â¬à¬Ò¬Ý¬Ö¬Þ, ¬ã ¬Ü¬Ñ¬Ü¬Ú¬Þ¬Ú ¬Ó¬í ¬ß¬Ö¬á¬â¬Ö¬Þ¬Ö¬ß¬ß¬à ¬Ó¬ã¬ä¬â¬Ö¬é¬Ñ¬Ö¬ä¬Ö¬ã¬î. ¬¯¬Ñ¬ê¬Ñ ¬Ü¬à¬Þ¬Ñ¬ß¬Õ¬Ñ ¬é¬Ñ¬ã¬ä¬ß¬í¬ç ¬ã¬í¬ë¬Ú¬Ü¬à¬Ó - ¬ï¬ä¬à ¬Ñ¬Ò¬ã¬à¬Ý¬ð¬ä¬ß¬à ¬ß¬Ö ¬ä¬à, ¬é¬ä¬à ¬Ó¬í ¬ß¬Ö¬á¬â¬Ö¬Þ¬Ö¬ß¬ß¬à ¬ß¬Ñ¬Ò¬Ý¬ð¬Õ¬Ñ¬Ö¬ä¬Ö ¬Ó ¬Ü¬Ú¬ß¬à¬Ü¬Ñ¬â¬ä¬Ú¬ß¬Ñ¬ç. ¬¹¬Ñ¬ã¬ä¬ß¬í¬Û ¬Õ¬Ö¬ä¬Ö¬Ü¬ä¬Ú¬Ó ¬à¬Ò¬Ý¬Ñ¬Õ¬Ñ¬Ö¬ä ¬á¬â¬Ñ¬Ü¬ä¬Ú¬é¬Ö¬ã¬Ü¬Ú¬Þ ¬à¬á¬í¬ä¬à¬Þ, ¬Ø¬Ú¬Ù¬ß¬Ö¬ß¬ß¬í¬Þ ¬à¬á¬í¬ä¬à¬Þ, ¬á¬â¬à¬æ¬Ö¬ã¬ã¬Ú¬à¬ß¬Ñ¬Ý¬î¬ß¬í¬Þ ¬à¬á¬í¬ä¬à¬Þ, ¬à¬á¬í¬ä¬à¬Þ, ¬ß¬Ñ¬Ó¬í¬Ü¬à¬Þ ¬Ú ¬Ù¬ß¬Ñ¬Ö¬Þ, ¬Ü¬Ñ¬Ü¬Ú¬Þ ¬ã¬á¬à¬ã¬à¬Ò¬à¬Þ ¬ã¬í¬ã¬Ü¬Ñ¬ä¬î ¬ã¬Ó¬Ö¬Õ¬Ö¬ß¬Ú¬ñ, ¬ß¬Ö¬à¬Ò¬ç¬à¬Õ¬Ú¬Þ¬å¬ð ¬Õ¬Ý¬ñ ¬Ó¬Ñ¬ê¬Ö¬Û ¬à¬á¬â¬Ö¬Õ¬Ö¬Ý¬Ö¬ß¬ß¬à¬Û ¬ã¬Ú¬ä¬å¬Ñ¬è¬Ú¬Ú. ¬±¬â¬ñ¬Þ¬à ¬ã¬Ö¬Ô¬à¬Õ¬ß¬ñ ¬Þ¬í ¬â¬Ö¬ê¬Ú¬Þ ¬Ó¬Ñ¬ê¬å ¬Ù¬Ñ¬Õ¬Ñ¬é¬å. ¬´¬à¬Ý¬î¬Ü¬à ¬ã¬à¬Ù¬Ó¬à¬ß¬Ú¬ä¬Ö¬ã¬î ¬ã ¬é¬Ñ¬ã¬ä¬ß¬í¬Þ ¬Õ¬Ö¬ä¬Ö¬Ü¬ä¬Ú¬Ó¬à¬Þ ¬Ú ¬ã¬à¬ä¬â¬å¬Õ¬ß¬Ú¬Ü¬Ú ¬ß¬Ñ¬ê¬Ö¬Û ¬æ¬Ú¬â¬Þ¬í ¬á¬à¬Þ¬à¬Ø¬Ö¬Þ ¬Ó¬Ñ¬Þ ¬Ý¬Ú¬é¬ß¬à.
¬¯¬Ñ¬ê¬Ö ¬à¬æ¬Ú¬è¬Ú¬Ñ¬Ý¬î¬ß¬à¬Ö ¬Õ¬Ö¬ä¬Ö¬Ü¬ä¬Ú¬Ó¬ß¬à¬Ö ¬Ñ¬Ô¬Ö¬ß¬ä¬ã¬ä¬Ó¬à ¬ä¬â¬å¬Õ¬Ú¬ä¬ã¬ñ, ¬Õ¬Ý¬ñ ¬ä¬à¬Ô¬à ¬é¬ä¬à¬Ò¬í ¬ß¬Ñ¬Û¬ä¬Ú ¬Ú¬ß¬æ¬à¬â¬Þ¬Ñ¬è¬Ú¬ð ¬Ú ¬Õ¬à¬Ü¬Ñ¬Ù¬Ñ¬ä¬Ö¬Ý¬î¬ã¬ä¬Ó¬Ñ, ¬Ü¬à¬ä¬à¬â¬í¬Ö ¬Ü¬Ý¬Ú¬Ö¬ß¬ä¬å ¬Ú¬Ý¬Ú ¬Ù¬Ñ¬Ü¬Ñ¬Ù¬é¬Ú¬Ü¬å ¬ß¬Ö¬à¬Ò¬ç¬à¬Õ¬Ú¬Þ¬í, ¬Ù¬Ñ¬ä¬Ö¬Þ ¬é¬ä¬à¬Ò¬í ¬å¬Ò¬Ö¬â¬Ö¬é¬î ¬ã¬Ó¬à¬ð ¬ã¬Ö¬Þ¬î¬ð, ¬ã¬Ó¬à¬ð ¬Õ¬Ö¬ñ¬ä¬Ö¬Ý¬î¬ß¬à¬ã¬ä¬î ¬Ú¬Ý¬Ú ¬ã¬Ó¬à¬Û ¬Ò¬Ú¬Ù¬ß¬Ö¬ã. ¬¥¬Ö¬ä¬Ö¬Ü¬ä¬Ú¬Ó¬ß¬à¬Ö ¬Ñ¬Ô¬Ö¬ß¬ã¬ä¬Ó¬à ¬Ô¬à¬ä¬à¬Ó¬à ¬á¬â¬Ö¬Õ¬à¬ã¬ä¬Ñ¬Ó¬Ú¬ä¬î ¬Ó¬Ñ¬Þ ¬ã¬Ú¬ã¬ä¬Ö¬Þ¬ß¬í¬Ö, ¬Ý¬å¬é¬ê¬Ú¬Ö, ¬â¬Ö¬Ù¬å¬Ý¬î¬ä¬Ñ¬ä¬Ú¬Ó¬ß¬í¬Ö, ¬ï¬Ü¬à¬ß¬à¬Þ¬Ú¬é¬ß¬í¬Ö, ¬ï¬æ¬æ¬Ö¬Ü¬ä¬Ú¬Ó¬ß¬í¬Ö, ¬Ü¬à¬Þ¬á¬Ý¬Ö¬Ü¬ã¬ß¬í¬Ö ¬Ú ¬Õ¬Ö¬Û¬ã¬ä¬Ó¬Ö¬ß¬ß¬í¬Ö ¬å¬ã¬Ý¬å¬Ô¬Ú ¬á¬à ¬â¬Ñ¬ã¬ã¬Ý¬Ö¬Õ¬à¬Ó¬Ñ¬ß¬Ú¬ð.
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JimmieShism  (95.154.xxx.221)  2021-03-17 21:01:03
<a href=https://stripewhite.com.ua/seminary/andrej-dujko/>¬¡¬ß¬Õ¬â¬Ö¬Û ¬¥¬å¬Û¬Ü¬à ¬ï¬Ù¬à¬ä¬Ö¬â¬Ú¬Ü¬Ñ </a>
¬±¬â¬à¬Ô¬à¬ß Xrumer  (109.234.xxx.37)  2021-03-10 09:12:10

<a href="https://kwork.ru/links/1017228/progon-khrumerom">¬±¬â¬à¬Ô¬à¬ß Xrumer</a>
ecotom  (37.9.xxx.159)  2021-03-07 02:54:52
https://eco-corporation.ru - ¬¬¬å¬á¬Ú¬ä¬î ¬ã¬Ö¬á¬ä¬Ú¬Ü ¬Õ¬Ý¬ñ ¬é¬Ñ¬ã¬ä¬ß¬à¬Ô¬à

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Richardjivig  (128.71.xxx.165)  2021-03-06 18:29:09
¬¯¬Ñ¬ê¬Ñ ¬æ¬Ú¬â¬Þ¬Ö¬ß¬ß¬Ñ¬ñ ¬å¬ã¬Ý¬å¬Ô¬Ñ ¬Ô¬â¬å¬Ù¬à¬á¬Ö¬â¬Ö¬Ó¬à¬Ù¬Ü¬Ú ¬Ò¬í¬Ý¬Ñ ¬à¬ã¬ß¬à¬Ó¬Ñ¬ß¬Ñ ¬Ó ¬è¬Ö¬Ý¬ñ¬ç ¬Ü¬à¬Þ¬æ¬à¬â¬ä¬Ñ ¬Ü¬Ý¬Ú¬Ö¬ß¬ä¬à¬Ó. ¬µ ¬ß¬Ñ¬ê¬Ö¬Û ¬Ù¬ß¬Ñ¬Þ¬Ö¬ß¬Ú¬ä¬à¬Û ¬Þ¬Ö¬Ø¬Õ¬å¬ß¬Ñ¬â¬à¬Õ¬ß¬à¬Û ¬Ü¬à¬Þ¬á¬Ñ¬ß¬Ú¬Ú ¬ª¬± ¬¬¬°¬¯¬³¬´¬¡¬¯¬´¬ª¬¯ ¬¡¬ß¬Ø¬Ö¬â¬à-¬³¬å¬Õ¬Ø¬Ö¬ß¬ã¬Ü ¬Ú¬Þ¬Ö¬Ö¬ä¬ã¬ñ ¬Ý¬Ú¬é¬ß¬í¬Û ¬Ñ¬Ó¬ä¬à¬Þ¬à¬Ò¬Ú¬Ý¬î¬ß¬í¬Û ¬á¬Ñ¬â¬Ü ¬Ñ ¬ä¬Ñ¬Ü¬Ø¬Ö ¬ê¬ä¬Ñ¬ä ¬Ü¬å¬â¬î¬Ö¬â¬à¬Ó. ¬¯¬Ñ¬ê¬Ñ ¬á¬â¬à¬Ú¬Ù¬Ó¬à¬Õ¬ã¬ä¬Ó¬Ö¬ß¬ß¬Ñ¬ñ ¬Ü¬à¬Þ¬á¬Ñ¬ß¬Ú¬ñ ¬Ô¬à¬ä¬à¬Ó¬Ñ ¬ã¬à¬Ó¬Ö¬â¬ê¬Ú¬ä¬î ¬Õ¬à¬ã¬ä¬Ñ¬Ó¬Ü¬å ¬ä¬à¬Ó¬Ñ¬â¬Ñ ¬Õ¬Ý¬ñ ¬Ó¬Ñ¬ê¬Ö¬Ô¬à ¬á¬â¬Ö¬Õ¬á¬â¬Ú¬ñ¬ä¬Ú¬ñ ¬Ó ¬Ò¬Ý¬Ñ¬Ô¬à¬á¬â¬Ú¬ñ¬ä¬ß¬à¬Ö ¬Ó¬â¬Ö¬Þ¬ñ. ¬¥¬Ý¬ñ ¬ï¬ä¬à¬Ô¬à ¬ä¬à¬Ý¬î¬Ü¬à ¬Ý¬Ú¬ê¬î ¬Ó¬í¬Ò¬Ö¬â¬Ú¬ä¬Ö ¬ã¬Ú¬ð ¬å¬ã¬Ý¬å¬Ô¬å. ¬£ ¬ä¬à¬Þ ¬ã¬Ý¬å¬é¬Ñ¬Ö ¬Ó¬Ñ¬ê ¬ä¬à¬Ó¬Ñ¬â ¬Ò¬å¬Õ¬Ö¬ä ¬Õ¬à¬ã¬ä¬Ñ¬Ó¬Ý¬Ö¬ß ¬à¬é¬Ö¬ß¬î ¬ä¬à¬é¬ß¬à ¬Ú ¬Ò¬í¬ã¬ä¬â¬à. ¬®¬à¬Ø¬ß¬à ¬â¬Ñ¬ã¬ã¬é¬Ú¬ä¬í¬Ó¬Ñ¬ä¬î ¬ß¬Ñ ¬ã¬Ó¬à¬Ö¬Ó¬â¬Ö¬Þ¬Ö¬ß¬ß¬à¬Ö ¬ã¬à¬á¬â¬à¬Ó¬à¬Ø¬Õ¬Ö¬ß¬Ú¬Ö, ¬á¬Ö¬â¬ã¬à¬ß¬Ñ¬Ý¬î¬ß¬í¬Ö ¬â¬Ö¬ê¬Ö¬ß¬Ú¬ñ ¬Ú ¬à¬ä¬Þ¬Ö¬ß¬ß¬à¬Ö ¬Ü¬Ñ¬é¬Ö¬ã¬ä¬Ó¬à ¬ê¬Ú¬â¬à¬Ü¬à¬æ¬à¬â¬Þ¬Ñ¬ä¬ß¬à¬Û ¬á¬Ö¬é¬Ñ¬ä¬Ú.
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